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Sample records for ischemic brain edema

  1. The role in thanatogenesis of generalized brain edema in ischemic cerebral infarction (computer-morphometric research

    Directory of Open Access Journals (Sweden)

    E. A. Dyadyk

    2012-12-01

    Full Text Available This work presents the results of computer-morphometric study of perivascular and pericellular free (oedematous spaces in brain cortex at death from the ischemic cerebral infarction and from reasons unconnected directly with cerebral pathology. It was revealed, that the mean area of perivascular spaces (vasogenic edema index at brain infarction in 13 times exceeds such at extracerebral pathology, and mean area of pericellular spaces (cytotoxic edema index – almost in 12 times, but also it substantially differs on the degree of variation (in 2,5 times higher, than area of perivascular spaces.

  2. [Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

    Science.gov (United States)

    Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

    2008-11-04

    To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

  3. Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2010-12-01

    Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

  4. The ischemic perinatal brain damage

    International Nuclear Information System (INIS)

    Crisi, G.; Mauri, C.; Canossi, G.; Della Giustina, E.

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis

  5. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  6. Osmotherapy in brain edema

    DEFF Research Database (Denmark)

    Grände, Per-Olof; Romner, Bertil

    2012-01-01

    Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect......, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain...... edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate...

  7. Reduction of superoxide dismutase activity correlates with visualization of edema by T[sub 2]-weighted MR imaging in focal ischemic rat brain

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    Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P H; Weinstein, P R; James, T L [California Univ., San Francisco, CA (United States); Yoshimoto, Takashi

    1994-01-01

    This study investigated the correlation between in vivo serial T[sub 2]-weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na[sup +]), and potassium ion (K[sup +]) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T[sub 2] signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na[sup +] and water and decreased K[sup +] contents occurred in the injured cortex, indicating that serial T[sub 2]-weighted MR imaging reflects the changes in water content and Na[sup +] and K[sup +] concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author).

  8. Reduction of superoxide dismutase activity correlates with visualization of edema by T2-weighted MR imaging in focal ischemic rat brain

    International Nuclear Information System (INIS)

    Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P.H.; Weinstein, P.R.; James, T.L.; Yoshimoto, Takashi.

    1994-01-01

    This study investigated the correlation between in vivo serial T 2 -weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na + ), and potassium ion (K + ) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T 2 signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na + and water and decreased K + contents occurred in the injured cortex, indicating that serial T 2 -weighted MR imaging reflects the changes in water content and Na + and K + concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author)

  9. Ischemic perinatal brain damage. Neuropathologic and CT correlations

    Energy Technology Data Exchange (ETDEWEB)

    Crisi, G; Mauri, C; Canossi, G; Della Giustina, E

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis. 31 refs.

  10. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

  11. Ischemic preconditioning protects against ischemic brain injury

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    Xiao-meng Ma

    2016-01-01

    Full Text Available In this study, we hypothesized that an increase in integrin αv ß 3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αv ß 3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αv ß 3 and vascular endothelial growth factor levels in the brain following ischemia.

  12. Sequential changes in ischemic edema following transient focal cerebral ischemia in rats; Magnetic resonance imaging study

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    Nagahiro, Shinji; Goto, Satoshi; Kogo, Kasei; Sumi, Minako; Takahashi, Mutsumasa; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    1994-07-01

    Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T[sub 2]-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T[sub 2] high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T[sub 2] high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema. (author).

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

    OpenAIRE

    Shotaro Michinaga; Yutaka Koyama

    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 vas...

  14. Brain edema associated with intracranial meningiomas

    International Nuclear Information System (INIS)

    Asahi, Minoru; Kikuchi, Haruhiko; Hirai, Osamu

    1992-01-01

    Brain edema associated with intracranial meningiomas was investigated on 80 patients, excluding recurrent cases. Statistically significant positive correlations with the degree of edema were found with large tumors, the convexity or parasagittal locations, the venous outflow disturbance, and the evidence of cortical disruption or peritumoral enhancement visualized on computed tomography or magnetic resonance imagings. Patients with a short clinical history and with angiographic evidence of hypervascularity tended to have edema, but there was no statistical significance. It is concluded that various factors are responsible for the edema associated with meningiomas and that it would be hard to determine the most important cause, since each factor plays a part edema production, spread, and resolution. (author)

  15. Brain edema associated with unruptured brain arteriovenous malformations

    International Nuclear Information System (INIS)

    Kim, Bum-soo; Sarma, Dipanka; Lee, Seon-Kyu; ter Brugge, Karel G.

    2009-01-01

    Brain edema in unruptured brain arteriovenous malformations (AVMs) is rare; this study examines (1) its frequency and clinical presentation, (2) imaging findings with emphasis on venous drainage abnormalities, and (3) implications of these findings on natural history and management. Presentation and imaging features of all unruptured brain AVMs were prospectively collected in our brain AVM database. Neurological findings, size, location, venous drainage pattern, presence of venous thrombosis, ectasia, or stenosis, and brain edema were specifically recorded. Treatment details of all patients with brain edema and their clinical and imaging follow-up were reviewed. Finally, a comparison was made between patients with and without edema. Brain edema was found in 13/329 unruptured brain AVMs (3.9%). Neurological deficit (46.2%), venous thrombosis (38.5%), venous ectasia (84.6%), stenosis (38.5%), and contrast stagnation in the draining veins (84.6%) were more frequent in patients with brain edema than without edema. Eight patients with brain edema received specific treatment (embolization = 5, surgery = 2, radiosurgery = 1). Clinical features correlated well with change in degree of edema in six. Three of five embolized patients were stable or showed improvement after the procedure. On follow-up, however, intracranial hemorrhage developed in three. Brain edema in unruptured brain AVMs is rare, 3.9% in this series. Venous outflow abnormalities are frequently associated and appear to contribute to the development of edema. Progressive nonhemorrhagic symptoms are also associated, with a possible increased risk of hemorrhage. Palliative embolization arrests the nonhemorrhagic symptoms in selected patients, although it may not have an effect on hemorrhagic risk. (orig.)

  16. Magnetic resonance imaging of experimental brain edema

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    Tanaka, Chuzo; Naruse, Shoji; Horikawa, Yoshiharu; Higuchi, Toshihiro; Ebisu, Toshihiko; Hirakawa, Kimiyoshi; Ohno, Yoshioki; Maki, Sou

    1987-04-01

    Experimental brain edema was produced by either cold injury or TET (triethyl-tin) intoxication in twenty-five Wistar rats, weighing about 250 g each, and then analyzed using MRI (magnetic resonance imaging). The MRI was carried out with a 0.1 Tesla clinical apparatus (Asahi Mark J), using a special coil (7 cm in diameter) devised for small animals in order to obtain SR, SE, IR, and calculated T/sub 1/ and T/sub 2/ images. A dose of 0.5 mmol/kg of Gd-DTPA was injected intravenously for the cold-injury edema, and MRIs of the rat brains were started immediately and obtained successively for 3 hours. MRI showed spatial resolution sufficient to differentiate the cortex from the caudate nucleus, even in such a small rat brain. Rat brains with TET intoxication (cytotoxic edema) showed a marked prolongation of T/sub 1/ and T/sub 2/ in the white matter. Consequently, the TET-intoxication images reflected these characteristic findings. Cold-induced edema showed an increased signal intensity in the injured cortex, the white matter, and the opposite white matter when compared with a normal brain. These changes correlate well with the previously reported in vitro data. When Gd-DTPA was administered to the rats with cold-induced edema, the signal intensity of the cold-injury lesion was significantly reduced. These changes were clearly demonstrated by the calculated T/sub 1/ images. To two rats we administered a dose of 0.5 mmol/kg of Gd-DTPA; The T/sub 1/ values for the cold-injury lesions, before and after the injection, were about 445 msec and about 200 msec respectively. These studies were useful not only in evaluating brain edema, but also in analysing the effect of Gd-DTPA on the brain edema.

  17. Spread of edema with brain tumors

    International Nuclear Information System (INIS)

    Hosoya, Takaaki

    1987-01-01

    Cerebral edema associated with brain tumors is visualized on CT as a hypodensity lesion involving mainly the white matter. The detailed features of its evolution were investigated in a review of CT examinations performed on 56 patients with brain tumors, with the following results. 1. The susceptibility to edema varied according to the types of fibers. Association fibers were more sensitive to edema than projection and commissural fibers. 2. The edema had a characteristic of spreading along not only the association fibers but also the projection and commissural fibers. 3. The spread of edema along the association fibers was interupted in sites of convergence of the fibers such as the external capsule and just beneath the central sulcus in the certrum semiovale. 4. In some cases with intra-axial tumors, the edema extended mainly in the projection and commissural fibers considered to be more resistant to it. For example, in cases with parietal and temporal intra-axial tumors, the posterior limb of the internal capsule was often more edematous than the external capsule. 5. The edema associated with meningioma had a characteristic of spreading mainly along the association fibers. When situated close to the corpus callosum, however, the commissural fibers were also involved. Edema extending mainly in the internal capsule, thus, was rarely observed in meningioma. 6. There was unique pattern of spread of edema in frontal tumors, which differentiated their CT pattern. Therefore, the location of the tumor could be correctly diagnosed by the pattern of the edema extension, even near the central sulcus or in the operculum region. (author)

  18. Drug Delivery to the Ischemic Brain

    Science.gov (United States)

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  19. Peritumoral brain edema in angiomatous supratentorial meningiomas

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Sørensen, Lars Peter; Dyrbye, Henrik

    2013-01-01

    The aim of this work was to study the vascular endothelial growth factor A (VEGF-A) pathway and peritumoral brain edema (PTBE) through comparison of non-angiomatous and angiomatous meningiomas. Meningiomas are common intracranial tumors, which often have PTBE. VEGF-A is an integral part of PTBE...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    2015-04-01

    Full Text Available 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.

  2. Effects of dexamethasone on brain edema

    International Nuclear Information System (INIS)

    Takemoto, Motohisa

    1982-01-01

    Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, 3 H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher 3 H-activity than the control. Furthermore, I.V. injection showed higher 3 H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of 3 H-dexamethasone in edematous brain, 3 H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher 3 H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of 3 H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema. (J.P.N.)

  3. Peritumoral edema associated with metastatic brain tumor

    International Nuclear Information System (INIS)

    Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

    1992-01-01

    Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

  4. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    Science.gov (United States)

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

    2010-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

  5. Sequential observations of brain edema with proton magnetic resonance imaging and spectroscopy

    International Nuclear Information System (INIS)

    Kamada, Kyousuke

    1996-01-01

    The purpose of this study was to assess the relationship between morphological and metabolic changes in brain edema using proton magnetic resonance systems. The serial changes during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance imaging ( 1 H MRI) and high-resolution proton MR spectroscopy ( 1 H MRS). We also analyzed the efficacy of AVS 1,2-bis (nicotinamide)-propane which can scavenge free radicals to the edema in this experiment. The edema was developing extensively via the corpus callosum in ipsi- and contralateral hemispheres as shown by gradually increased signal intensity on 1 H MRI. 1 H MRS initially showed accumulation of acetate and lactate, and transient increasing of glutamine. After 24 hours, the increased glutamine decreased below the control, alanine increased, and N-acetyl aspartate decreased with the edema development. AVS-treatment significantly suppressed edema development, increases of lactate and alanine and decreases of N-acetyl aspartate. We suggest that the cold-induced lesion contains anaerobic glycolysis deterioration and results in severe brain tissue breakdown. AVS is proved valuable for the treatment of this edema lesion. Clinical 1 H MRS showed prolonged lactate elevation and significant decreases of other metabolites in human ischemic stroke edema. In peritumoral edema, decreased N-acetyl aspartate gradually improved, and slightly elevated lactate disappeared after tumor removal. 1 H MRS feasibly characterizes the ischemic and peritumoral edema and makes a quantitative analysis in human brain metabolism. We believe the combined 1 H MRI and MRS study is a practical method to monitor the brain conditions and will make it easy and possible to find new therapeutic agents to some brain disorders. (author)

  6. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

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    Machado Livia S

    2005-08-01

    Full Text Available Abstract Background While gelatinase (MMP-2 and -9 activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. Results Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9 expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. Conclusion The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.

  7. Effect of AVP on brain edema following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    XU Miao; SU Wei; HUANG Wei-dong; LU Yuan-qiang; XU Qiu-ping; CHEN Zhao-jun

    2007-01-01

    Objective: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. Methods: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS≤ 8) and moderate traumatic brain injury group (MTBI, GCS>8).Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan.Results: plasma AVP levels (ng/L) were (mean±SD): control, 3.06±1.49; MTBI, 38.12±7.25; and STBI, 66.61±17.10.The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P<0.01). And the AVP level was correlated with the severity (STBI r=0.919, P<0.01; MTBI r=0.724, P<0.01) and the duration of brain edema (STBI r=0.790, P<0.01; MTBI r=0.712, P<0.01). Conclusions: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

  8. Alterations in diffusion and perfusion in the pathogenesis of peritumoral brain edema in meningiomas

    International Nuclear Information System (INIS)

    Bitzer, M.; Klose, U.; Naegele, T.; Voigt, K.; Geist-Barth, B.; Schick, F.; Claussen, C.D.; Morgalla, M.

    2002-01-01

    Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant (p 2 . The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10 -3 vs 1.55 x 10 -3 mm 2 /s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema. (orig.)

  9. Proton nuclear magnetic resonance studies on brain edema

    International Nuclear Information System (INIS)

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

    1982-01-01

    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. Mathematical modelling of blood-brain barrier failure and edema

    Science.gov (United States)

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

    2015-11-01

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

  11. Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

    Science.gov (United States)

    Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

    2013-02-01

    To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

  12. CT findings in brain edema following the administration of corticosteroids

    International Nuclear Information System (INIS)

    Seki, Yojiro; Kumagai, Norimoto; Aiba, Tadashi

    1979-01-01

    Computed tomography (CT) is the first noninvasive method available for directly visualizing brain edema in man. On CT scans perifocal edema is shown as an area of low density surrounding a lesion. The purpose of this report is to evaluate the effect of corticosteroids on brain edema as seen by CT (HITACHI CT-H 250). Nine patients with brain-tumor and one with brain-abscess were treated with betamethasone for about ten days (dosage started with 12 - 16 mg/day, and tapered). In eight cases, and improvement in the neurological findings was observed. An impressive reduction of peritumoral edema was shown on CT scans in six of these eight cases. There was, however, no significant correlation between the degree of the reduction of edema on CT and that of the improvement in neurological findings. The mode of the CT number in the region of edema did not differ significantly between pre- and post-steroid treatment in the cases showing a recognizable reduction of edema on CT. This failure to change is probably due to the insufficient mechanical accuracy of the CT scanner at the present stage of technology. Through our experiences, it seems that CT is one of the most promising tools for a dynamic study of brain edema in man. (author)

  13. CT findings in brain edema following the administration of corticosteroids

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Y; Kumagai, N; Aiba, T [Toranomon Hospital, Tokyo (Japan)

    1979-03-01

    Computed tomography (CT) is the first noninvasive method available for directly visualizing brain edema in man. On CT scans perifocal edema is shown as an area of low density surrounding a lesion. The purpose of this report is to evaluate the effect of corticosteroids on brain edema as seen by CT (HITACHI CT-H 250). Nine patients with brain-tumor and one with brain-abscess were treated with betamethasone for about ten days (dosage started with 12 - 16 mg/day, and tapered). In eight cases, and improvement in the neurological findings was observed. An impressive reduction of peritumoral edema was shown on CT scans in six of these eight cases. There was, however, no significant correlation between the degree of the reduction of edema on CT and that of the improvement in neurological findings. The mode of the CT number in the region of edema did not differ significantly between pre- and post-steroid treatment in the cases showing a recognizable reduction of edema on CT. This failure to change is probably due to the insufficient mechanical accuracy of the CT scanner at the present stage of technology. Through our experiences, it seems that CT is one of the most promising tools for a dynamic study of brain edema in man.

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

    Science.gov (United States)

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

    2014-11-01

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Brain anti-cytoxic edema agents.

    Science.gov (United States)

    Kimelberg, H K; Barron, K D; Bourke, R S; Nelson, L R; Cragoe, E J

    1990-01-01

    The work described in this chapter has indicated that improved outcome from an experimental head injury model can be achieved by drugs which are non-diuretic derivatives of loop diuretics, namely indanyl and fluorenyl compounds which are derivatives of ethacrynic acid. These drugs were originally identified by us on the basis of their efficacy in inhibiting [K+]-stimulated, HCO3(-)-dependent swelling of brain cerebrocortical slices. Swelling of glial cells (astrocytes) has long been known to be associated with such slice swelling and astrocyte swelling is a major locus of cytotoxic or cellular brain edema. Qualitative and quantitative electron microscope studies have shown that L644,711, a particularly effective member of the fluorenyl class of drugs, inhibits astrocytic swelling associated with an experimental animal head injury model. We have suggested that astrocytic swelling in pathological states may be partly due to activation of Cl-/HCO3- and Na+/H+ exchange systems driven by increased astrocytic intracellular hydration of CO2, and recent work has indeed shown that the ability of the indanyl and fluorenyl drugs to inhibit brain slice swelling and protect against head injury correlates closely with their ability to inhibit Cl-/HCO3- exchange. All these data suggest that astrocytic swelling, which seems to precede neuronal degeneration and breakdown of the blood-brain barrier, is deleterious and that prevention of such swelling can lead to effective therapy. We have used primary astrocytic cultures to explore reasons why astrocytic swelling could be harmful. Exposing such astrocytes to hypotonic medium causes rapid swelling with a slower return to normal volume in the continued presence of hypotonic medium, a process known as regulatory volume decrease or RVD. Such RVD is associated with marked release of several amino acids, including L-glutamate. L644,711 and other Cl-/HCO3- transport inhibitors such as SITS and furosemide, but not the selective Na+ + K+ + 2

  16. Purinergic receptor stimulation reduces cytotoxic edema and brain infarcts in mouse induced by photothrombosis by energizing glial mitochondria.

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    2010-12-01

    Full Text Available Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5' diphosphate (2-MeSADP, an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y(1R. At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP(3-dependent Ca(2+ release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries.

  17. MRI in ischemic brain diseases

    International Nuclear Information System (INIS)

    Steinbrich, W.; Friedmann, G.; Pawlik, G.; Boecher-Schwarz, H.G.; Heiss, W.D.

    1986-01-01

    The results of MRI and CT in 55 patients with brain infarcts were compared; in 26 of these cases an additional PET examination was obtained in order to study the regional glucose utilisation. MRI was superior to CT, demonstrating 11% more of the infarcts, particularly during the first 24 hours, in small lesions confined to the grey or subcortical white matter and in infratentorial ischemic lesion. On the other hand, only CT was able to show fresh hemorrhage, although MRI was the method of choice to demonstrate old blood collections. To characterise the follow up of an infarct, CT and MRI were similar, except the marginal contrast enhancement sometimes demonstrated by CT studies between the 2nd and 4th week after stroke event. PET was inferior to show details because of its poorer spatial resolution, but anyhow had a high sensitivity and provided additional informations concerning secondary inactivations of brain areas not directly damaged. Additionally PET was able to demonstrate areas of anaerobic glycolysis and lesions of diminished glucose utilisation in TIAs. Small areas of gliosis in the white matter of the cerebral hemispheres were frequently found in patients with cerebro-vascular diseases; they were best shown by MRI, but do not correlate with the extent of vascular stenoses or occlusions, shown by angiography. (orig) [de

  18. Quantification of convection-enhanced delivery to the ischemic brain

    International Nuclear Information System (INIS)

    Haar, Peter J; Broaddus, William C; Chen, Zhi-jian; Gillies, George T; Fatouros, Panos P; Corwin, Frank D

    2010-01-01

    Convection-enhanced delivery (CED) could have clinical application in the delivery of neuroprotective agents following ischemic stroke. However, ischemic brain tissue changes such as cytotoxic edema, in which cellular swelling decreases the fractional volume of the extracellular space, would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. We sought to predict and characterize these effects using the magnetic resonance contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a model therapeutic agent. CED was observed using MRI in a normal rat brain and in a middle cerebral artery (MCA) occlusion rat model of brain ischemia. Gd-DTPA was infused to the caudate putamen in the normal rat (n = 6) and MCA occlusion model (n = 6). In each rat, baseline apparent diffusion coefficient images were acquired prior to infusion, and T1 maps were then acquired 13 times throughout the duration of the experiment. These T1 maps were used to compute Gd-DTPA concentrations throughout each brain. In the MCA occlusion group, CED delivered Gd-DTPA to a comparatively larger volume with lower average tissue concentrations. Following the infusion, the total content of Gd-DTPA decreased more slowly in the MCA occlusion group than in the normal group. This quantitative characterization confirms that edematous ischemic tissue changes alter the distribution of agents by CED. These findings may have important implications for CED in the treatment of brain injury, and will assist in future efforts to model the distribution of therapeutic agents

  19. Edema

    Science.gov (United States)

    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 ...

  20. The spreading of focal brain edema induced by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ferszt, R.; Neu, S.; Cervos-Navarro, J.; Sperner, J.

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells. (orig./AJ) [de

  1. Spreading of focal brain edema induced by ultraviolet irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ferszt, R; Neu, S; Cervos-Navarro, J; Sperner, J [Freie Univ. Berlin (Germany, F.R.). Inst. fuer Neuropathologie

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy

    Science.gov (United States)

    Yano, Hajime; Takahashi, Hisaaki; Yoshimoto, Kouhei; Tsuda, Shinji; Fujiyama, Kenta; Izumo-Shimizu, Yusuke; Motoie, Ryota; Ito, Masanori; Tanaka, Junya; Ishii, Eiichi

    2017-01-01

    Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE), and aquaporin 4 (AQP4) plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg) treated group than in the nontreated (saline) group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function. PMID:29234383

  4. Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Yoshiaki Yano

    2017-01-01

    Full Text Available Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE, and aquaporin 4 (AQP4 plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg treated group than in the nontreated (saline group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function.

  5. Generalised brain edema and brain infarct in ergotamine abuse: Visualization by CT, MR and angiography

    International Nuclear Information System (INIS)

    Toedt, C.; Hoetzinger, H.; Salbeck, R.; Beyer, H.K.

    1989-01-01

    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. (orig.) [de

  6. Neurovascular regulation in the ischemic brain.

    Science.gov (United States)

    Jackman, Katherine; Iadecola, Costantino

    2015-01-10

    The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

  7. Edema

    Science.gov (United States)

    ... term protein deficiency. An extreme lack (deficiency), of protein in your diet over a long period of time can lead to fluid accumulation and edema. Risk factors If you are pregnant, your body retains more sodium and water than ...

  8. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    International Nuclear Information System (INIS)

    Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Hirakawa, Kimiyoshi

    1987-01-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo 1 H- and 31 P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the 1 H-MRIs and 31 P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the 31 P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the 31 P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the 31 P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly. (J.P.N.)

  9. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, S; Higuchi, T; Horikawa, Y; Tanaka, C; Hirakawa, K

    1987-02-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo /sup 1/H- and /sup 31/P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the /sup 1/H-MRIs and /sup 31/P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the /sup 31/P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the /sup 31/P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the /sup 31/P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly.

  10. Neonatal ischemic brain injury: what every radiologist needs to know

    International Nuclear Information System (INIS)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E.

    2012-01-01

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  11. MRI findings of acute cerebral swelling and brain edema in the acute stage

    International Nuclear Information System (INIS)

    Oki, Hideo; Ueda, Shin; Matsumoto, Keizo; Kashihara, Michiharu; Furuichi, Masashi.

    1988-01-01

    We report two cases, one of acute cerebral swelling and the other with a major stroke, whose MRI has shown very interesting findings. Case 1, a 32-year-old male, was admitted to our service because of a lowering of his consciousness immediately after a head injury. On admission, the patient was semicomatous (E 1 M 2 V 1 , with anisocoria (R > L). His plain skull X-ray was normal. A CT scan, however, demonstrated right isodensity hemispheric swelling associated with a subarachnoid hemorrhage in the right Sylvian fissure. A right carotid angiogram showed no vascular disorders. MR imaging of the spin density demonstrated a hyperintensitive thickening of the gray matter in the whole right hemisphere. Case 2, a 58-year-old female, was admitted because of a sudden onset of loss of consciousness, with right hemiparesis and dysarthria. On admission, her consciousness was semicomatous (E 1 M 3 V 1 ), and it deteriorated to a deep coma 1 hour later. A CT scan demonstrated a diffuse left hemispheric low density, with a finding of hemorrhagic infarction in the basal ganglia. MR imaging of the spin density showed a hyperintensitive thickening of the gray matter resembling that of Case 1. The findings of the spin-echo images of our two cases showed a hyperintensitive thickening of the gray matter in both. The hyperintensity and thickening of the gray matter apparently indicated a sort of hyperemia and brain edema. These findings led us to suspect that the hyperemia associated with acute cerebral swelling and ischemic brain edema of our two cases originated in the gray matter, although it has been considered that the pathogenesis of acute cerebral swelling is not known and that brain edema, especially vasogenic edema, will mostly develop in the white matter rather than in the gray matter. (author)

  12. Water in Brain Edema : Observations by the Pulsed Nuclear Magnetic Resonance Technique

    NARCIS (Netherlands)

    GO, KG; Edzes, HT

    The state of water in three types of brain edema and in normal brain of the rat was studied by the pulsed nuclear magnetic resonance (NMR) technique. In cold-induced edema and in osmotic edema both in cortex and in white matter, the water protons have longer nuclear magnetic relaxation times than in

  13. Ischemic Tolerance of the Brain and Spinal Cord: A Review.

    Science.gov (United States)

    Yunoki, Masatoshi; Kanda, Takahiro; Suzuki, Kenta; Uneda, Atsuhito; Hirashita, Koji; Yoshino, Kimihiro

    2017-11-15

    Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

  14. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  15. Effects of glycyrrhizin pre-treatment on transient ischemic brain ...

    African Journals Online (AJOL)

    Effects of glycyrrhizin pre-treatment on transient ischemic brain injury in mice. ... on transient ischemic brain injury in mice. Chiyeon Lim, Sehyun Lim, Young-Jun Lee, Bokcheul Kong, Byoungho Lee, Chang-Hyun Kim, Buyeo Kim, Suin Cho ... induced brain damage. Keywords: Glycyrrhizin, licorice, stroke, apoptosis ...

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

    Science.gov (United States)

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

    2015-07-01

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

  17. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally......(6266) (p edema in mice with ALF....

  18. Neonatal ischemic brain injury: what every radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

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

    Science.gov (United States)

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

    2016-09-01

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

  20. Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

    Directory of Open Access Journals (Sweden)

    Svitlana Garbuzova-Davis

    Full Text Available Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas.In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO, significant BBB alterations characterized by large Evans Blue (EB parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices.These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.

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

    Science.gov (United States)

    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

  2. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema...

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

    Science.gov (United States)

    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.

  4. Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

    Science.gov (United States)

    Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

    2016-05-15

    Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Ginsenoside Rg1 improves ischemic brain injury by balancing ...

    African Journals Online (AJOL)

    Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

  6. Effects of dexamethasone on brain edema. Uptake and distribution of tritiated (/sup 3/H) dexamethasone in cold induced edema

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Motohisa [Okayama Univ. (Japan). School of Medicine

    1982-06-01

    Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, /sup 3/H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher /sup 3/H-activity than the control. Furthermore, I.V. injection showed higher /sup 3/H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of /sup 3/H-dexamethasone in edematous brain, /sup 3/H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher /sup 3/H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of /sup 3/H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema.

  7. The effect of pre-nutrition of hydroalcoholic extractof Origanum vulgare on brain edema and neurologic deficits in a rat stroke model

    Directory of Open Access Journals (Sweden)

    Meysam Foroozandeh

    2015-10-01

    Full Text Available Background and Aim: Stroke is one of the most important factors of mortality and disability in the world. Free radicals are produced following ischemic stroke and they play a central role in breaking the blood-brain barrier and  causing brain edema formation. The aim of the current study was to evaluate the effect of hydro- alcoholic extract of Origanum vulgare on brain edema and neurologic deficit in a rat stroke model. Materials and Methods: In thisexperimental study, 35 male Wistar rats were randomly divided into 5 equal groups.  The first  two groups (control and Sham received distilled water, while three treatment groups received oral Origanum vulgare extract for 30days (50,75and 100 mg/kgdaily, respectively.  Two hours after the last dose of Origanum vulgare extract,each main group underwent  a 60 min middle cerebral artery occlusion.  Then, the assessment of blood brain edema, and neurologic deficits analysis were done . Brain edema (brain water content was analyzed by One-Way ANOVA using LSD method and neurologic deficits analysis by means of Mann-Whitney U, and P<0.05 was taken as the significant level. Results: Origanum vulgare extract reduced brain edema in the experimental groups of 50 (82.49±0.47, 75 (80.89±0.63 and 100 mg/kg/day (80.80±0.66 compared to the control group (84.46±0.67. The neurologic deficit scores in the experimental groups of 75and 100mg/kg/day, compared with control group, but neurologic deficit scores did not affect the group receiving the dose 50 mg/kg. Conclusion:  The obtained data indicate that Origanum vulgar extract via reduction of brain edema and neurologic deficits scorescan have a protective effect on the stroke model.

  8. Peritumoral brain edema in intracranial tumor evaluated by CT perfusion imaging

    International Nuclear Information System (INIS)

    Shi Yuxin; Xu Jianfeng

    2005-01-01

    Objective: To semi-quantitatively evaluate the cerebral perfusion in the peritumoral brain edema of cerebral tumors using CT perfusion imaging. Methods: Twenty-one patients with peritumoral brain edema (including pathologically confirmed meningiomas n=4, metastasis n=10, gliomas n=7) were examined by CT perfusion imaging. The regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and mean transit time (MTT) were calculated for peritumoral brain edema and the contralateralwhite matter. The rCBF and rCBV were compared between peritumoral brain edema and the contralateral white matter. The mean ratios (edema/contralateral white matter) of rCBF and rCBV were compared among the three tumors. Results: The rCBF and rCBV of peritumoral brain edema were significantly lower than those of contralateral white matter in patients with meningiomas and metastasis (rCBF: t=2.92 and 3.82, P 0.05). The mean ratios (edema/contralateralwhite matter) of rCBF and rCBV were not significantly different between meningiomas and metastasis (t=0.23 and 0.73, P>0.05), but both of them were significantly lower than those of gliomas (t=3.05 and 3.37, P<0.01, 0.005). Conclusion: The rCBF and rCBV in peritumoral brain edema were significantly lower than those of contralateral white matter in patients with meningiomas and metastasis, while almost the same with or higher than those of contralateral white matter in patients with gliomas. CT perfusion can provide quantitative information of blood flow in peritumoral brain edema, and is useful in the diagnosis and follow-up of cerebral tumors. (authors)

  9. Mathematical model in post-mortem estimation of brain edema using morphometric parameters.

    Science.gov (United States)

    Radojevic, Nemanja; Radnic, Bojana; Vucinic, Jelena; Cukic, Dragana; Lazovic, Ranko; Asanin, Bogdan; Savic, Slobodan

    2017-01-01

    Current autopsy principles for evaluating the existence of brain edema are based on a macroscopic subjective assessment performed by pathologists. The gold standard is a time-consuming histological verification of the presence of the edema. By measuring the diameters of the cranial cavity, as individually determined morphometric parameters, a mathematical model for rapid evaluation of brain edema was created, based on the brain weight measured during the autopsy. A cohort study was performed on 110 subjects, divided into two groups according to the histological presence or absence of (the - deleted from the text) brain edema. In all subjects, the following measures were determined: the volume and the diameters of the cranial cavity (longitudinal and transverse distance and height), the brain volume, and the brain weight. The complex mathematical algorithm revealed a formula for the coefficient ε, which is useful to conclude whether a brain edema is present or not. The average density of non-edematous brain is 0.967 g/ml, while the average density of edematous brain is 1.148 g/ml. The resulting formula for the coefficient ε is (5.79 x longitudinal distance x transverse distance)/brain weight. Coefficient ε can be calculated using measurements of the diameters of the cranial cavity and the brain weight, performed during the autopsy. If the resulting ε is less than 0.9484, it could be stated that there is cerebral edema with a reliability of 98.5%. The method discussed in this paper aims to eliminate the burden of relying on subjective assessments when determining the presence of a brain edema. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  10. Cellular characterization of the peritumoral edema zone in malignant brain tumors

    International Nuclear Information System (INIS)

    Engelhorn, T.; Schwarz, M.A.; Savaskan, N.E.

    2009-01-01

    Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment. (author)

  11. Synthesis of 11C-methylated inulin as a radiopharmaceutical for imaging brain edema and pulmonary edema

    International Nuclear Information System (INIS)

    Hara, Toshihiko; Iio, Masaaki; Inagaki, Keizo

    1988-01-01

    11 C-methylated inulin, supposedly useful for imaging of brain edema and pulmonary edema, was prepared using cyclotron produced 11 CO 2 . The synthesis consists of the production of 11 C-methyl iodide and its coupling with inulin alkoxide sodium in dimethylsulfoxide as solvent. 11 C labeled inulin was purified by alcohol precipitation. The radiochemical yield of pure 11 C-inulin was 34% of 11 CO 2 30 min after the end of bombardment. The blood clearance and body distribution of 11 C was observed in rabbits after i.v. injection of 11 C-inulin. The blood clearance curve was composed of a sum of three exponential functions. The gamma camera image showed that the 11 C activity in blood moved quickly to kidneys and urine and a small dose of radioactivity remained persistently in edematous tissues, i.e. the edematous lung tissues produced by oleic acid treatment. (orig.)

  12. Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

    Science.gov (United States)

    Zhang, Hai-Tao; Zhang, Ping; Gao, Yi; Li, Chen-Long; Wang, Hong-Jun; Chen, Ling-Chao; Feng, Yan; Li, Rui-Yan; Li, Yong-Li; Jiang, Chuan-Lu

    2017-01-01

    Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

  13. The effect of infectious brain edema on NMDA receptor binding in rat's brain

    International Nuclear Information System (INIS)

    Cheng Guansheng; Chen Jianfang; Chen Xiang

    1997-01-01

    PURPOSE: The effect of the infectious brain edema (IBE) induced by Bordetella Pertussis (BP) on the specific binding of 3 H MK-801 in rat's brain in vivo was determined. METHODS: BP was injected via left internal carotid artery in rat model of infectious brain edema. Male SD rats were divided into three groups: 1) Group control (NS, n = 11); 2) Group IBF (BP, n = 12); 3) Group pretreatment of MK-801 + PB (MK-801, n = 4). Normal saline or BP 0.2 ml/kg was injected into left internal carotid artery in NS and BP group respectively. MK-801 0.5 mg/kg per day was injected i.p. two days before injection of BP in group MK-801. Rats were killed by decapitation at 24 hours after injection of BP. The specific binding of N-methyl-D-aspartate (NMDA) receptor were measured with 3 H-MK-801 in the neuronal membrane of cerebral cortex. The Scatchard plots were performed. RESULTS: The B max values were 0.623 +- 0.082 and 0.606 +- 0.087 pmol/mg protein in group NS and BP respectively (t = 0.48, P>0.05). The Kd values were 43.1 +- 4.2 and 30.5 +- 3.0 nmol/L in group NS and BP respectively (t = 7.8, P<0.05). The specific binding of NMDA receptor was decreased by pretreatment of MK-801. CONCLUSIONS: The total number of NMDA receptor had not changed, whereas its affinity increased significantly in the model of brain edema induced by pertussis bacilli in rat. The increase of affinity of NMDA receptor can be blockaded by MK-801 pretreatment in vivo

  14. Magnetic resonance imaging of cold injury-induced brain edema in rats

    International Nuclear Information System (INIS)

    Houkin, Kiyohiro; Abe, Hiroshi; Hashiguchi, Yuji; Seri, Shigemi.

    1996-01-01

    The chronological changes of blood-brain barrier disruption, and diffusion and absorption of edema fluid were investigated in rats with cold-induced brain injury (vasogenic edema) using magnetic resonance imaging. Contrast medium was administered intravenously at 3 and 24 hours after lesioning as a tracer of edema fluid. Serial T 1 -weighted multiple-slice images were obtained for 180 minutes after contrast administration. Disruption of the blood-brain barrier was more prominent at 24 hours after lesioning than at 3 hours. Contrast medium leaked from the periphery of the injury and gradually diffused to the center of the lesion. Contrast medium diffused into the corpus callosum and the ventricular system (cerebrospinal fluid). Disruption of the blood-brain barrier induced by cold injury was most prominent at the periphery of the vasogenic edema. Edema fluid subsequently extended into the center of the lesion and was also absorbed by the ventricular system. Magnetic resonance imaging is a useful method to assess the efficacy of therapy for vasogenic edema. (author)

  15. Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Bodsch, W; Huerter, T; Hossmann, K A [Max-Planck-Institut fuer Hirnforschung, Koeln (Germany, F.R.). Forschungsstelle fuer Hirnkreislauf-Forschung

    1982-10-07

    An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema.

  16. Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

    International Nuclear Information System (INIS)

    Bodsch, W.; Huerter, T.; Hossmann, K.-A.

    1982-01-01

    An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema. (Auth.)

  17. H-1 chemical shift imaging characterization of human brain tumor and edema

    NARCIS (Netherlands)

    Sijens, PE; Oudkerk, M

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) H-1 chemical shift imaging results at different repetition times (TR = 1500 and 5000 ms; T1: n = 19) and

  18. Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.

    Science.gov (United States)

    Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

    2014-05-01

    Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    John Thundyil

    Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

  20. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  1. Neurovascular Regulation in the Ischemic Brain

    OpenAIRE

    Jackman, Katherine; Iadecola, Costantino

    2015-01-01

    Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active respons...

  2. Mechanisms of gender-linked ischemic brain injury

    Science.gov (United States)

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

    2010-01-01

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

  3. The Antiedema Effect of Intracisternal Hyperosmolar Albumine on Experimental Created Brain Edema

    Directory of Open Access Journals (Sweden)

    Ayhan Tekiner

    2010-01-01

    Full Text Available Aim: The brain edema caused by central nervous system diseases and trauma is an important reason of morbidity and mortality currently. Although the most of physiopathology of traumatic brain edema has been elucidated through many clinical and laboratory studies, the treatment of edema couldn?t been standardized. For this purpose, from past to the present although many treatment principles have been accepted, also different treatment agents are being used. Material and Methods: In this experimental study thirty six New Zealander rabbits weighing between 2.2 and 2.8 kg were used. Craniectomi was applied to the subjects and gravity was dropped from high in order to develop traumatic brain edema. The subjects were divided into six groups and hyperosmolar albumine was given to each group on different time periods. It was Aim: ed to resolve the edema by drawing the edema liquid to subarachnoid distance by giving human albumin a physiologic macromolecule through cysterna manga. The efficacy of tretment was evaluated through two parameters: the first cerebrospinal fluid osmolality and the second the rate of brain tissue fluid. Results: Cerebrospinal fluid osmolality and brain tissue fluid ratio gained at the result of the study were statistical evaluated by  Kruskal-Wallis nonparametric ANOVA test and Mann-Whitney U test. p value<0,05 was accepted statistical significant. Conclusions: When compared the Results : of the study groups the difference was significant between trauma and control group and the difference was relatively close to the control group at the treatment group. The treatment was significantly efficient at the groups which were applied hyperosmolar albumine two or three times in the first 72 hours after trauma. According to these Results : we can declare this experimental study has reached to the purpose and can contribute to future studies about the same subject.

  4. Silent ischemic brain lesions after transcatheter aortic valve replacement : lesion distribution and predictors

    NARCIS (Netherlands)

    Samim, Mariam; Hendrikse, Jeroen; van der Worp, H. Bart; Agostoni, Pierfrancesco; Nijhoff, Freek; Doevendans, Pieter A.; Stella, Pieter R.

    Silent ischemic brain lesions and ischemic stroke are known complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate the occurrence and distribution of TAVR-related silent ischemic brain lesions using diffusion-weighted magnetic resonance imaging (DWI). Consecutive

  5. Structural MRI markers of brain aging early after ischemic stroke.

    Science.gov (United States)

    Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

    2017-07-11

    To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  6. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

    Directory of Open Access Journals (Sweden)

    Kenne Ellinor

    2012-01-01

    Full Text Available Abstract Background Brain edema as a result of secondary injury following traumatic brain injury (TBI is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI. Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice.

  7. A STUDY ON PERITUMORAL BRAIN EDEMA AROUND MENINGIOMAS BY MRI AND CONTRAST CT

    NARCIS (Netherlands)

    GO, KG; KAMMAN, RL; WILMINK, JT; MOOYAART, EL

    1994-01-01

    In the present study upon 9 meningiomas, the volume of peritumoral brain edema was calculated by integration of the cross-sectional edematous areas on serial MRI slices. It was zero in 3 cases and ranged from 11 to 176.4 ml in the other cases. There was disruption of the cortex in all cases, ranging

  8. Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2017-01-01

    Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone is also synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain. Apart from performing crucial reproductive functions, it also plays a pivotal role in neurogenesis, regeneration, cognition, mood, inflammation, and myelination in the CNS. A substantial body of experimental evidence from animal models documents the neuroprotective role of P4 in various CNS injury models, including ischemic stroke. Extensive data have revealed that P4 elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies. Data regarding the neuroprotective role of P4 in ischemic stroke are of great interest due to their potential clinical implications. In this review, we succinctly discuss the biosynthesis of P4 and distribution of P4 receptors (PRs) in the brain. We summarize our work on the general mechanisms of P4 mediated via the modulation of different PR and neurotransmitters. Finally, we describe the neuroprotective mechanisms of P4 in ischemic stroke models and related clinical prospects.

  9. Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

    Science.gov (United States)

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

    2014-03-01

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

  10. Quantitative Apparent Diffusion Coefficients in the Characterization of Brain Tumors and Associated Peritumoral Edema

    International Nuclear Information System (INIS)

    Server, A.; Schellhorn, T.; Nakstad, P.H.; Kulle, B.; Maehlen, J.; Kumar, T.; Josefsen, R.; Langberg, C.W.

    2009-01-01

    Background: Conventional magnetic resonance (MR) imaging has a number of limitations in the diagnosis of the most common intracranial brain tumors, including tumor specification and the detection of tumoral infiltration in regions of peritumoral edema. Purpose: To prospectively assess if diffusion-weighted MR imaging (DWI) could be used to differentiate between different types of brain tumors and to distinguish between peritumoral infiltration in high-grade gliomas, lymphomas, and pure vasogenic edema in metastases and meningiomas. Material and Methods: MR imaging and DWI was performed on 93 patients with newly diagnosed brain tumors: 59 patients had histologically verified high-grade gliomas (37 glioblastomas multiforme, 22 anaplastic astrocytomas), 23 patients had metastatic brain tumors, five patients had primary cerebral lymphomas, and six patients had meningiomas. Apparent diffusion coefficient (ADC) values of tumor (enhancing regions or the solid portion of tumor) and peritumoral edema, and ADC ratios (ADC of tumor or peritumoral edema to ADC of contralateral white matter, ADC of tumor to ADC of peritumoral edema) were compared with the histologic diagnosis. ADC values and ratios of high-grade gliomas, primary cerebral lymphomas, metastases, and meningiomas were compared by using ANOVA and multiple comparisons. Optimal thresholds of ADC values and ADC ratios for distinguishing high-grade gliomas from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Statistically significant differences were found for minimum and mean of ADC tumor and ADC tumor ratio values between metastases and high-grade gliomas when including only one factor at a time. Including a combination of in total four parameters (mean ADC tumor, and minimum, maximum and mean ADC tumor ratio) resulted in sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 72.9, 82.6, 91.5, and 54.3% respectively. In the ROC curve analysis

  11. [Unilateral acute pulmonary edema and ischemic myocardial process: a case report].

    Science.gov (United States)

    Bentaleb, A; Tagu, P; Vascaut, L

    2008-08-01

    Unilateral acute pulmonary oedema (APO) is a rare radioclinical finding. It occurs secondary to multiple specific and rare pathological processes. Functional ischemic mitral regurgitation (FIMR) secondary to myocardial necrosis is one of the rare aetiologies involved in its pathogenesis. This concerns a 94-year-old male patient with a history of myocardial infarction who presented with a clinical picture of unilateral APO secondary to functional mitral regurgitation as a complication of myocardial necrosis. In addition to the clinical presentation and unilateral radiological findings, the diagnosis was based essentially on the electrocardiographic tracing, as well as changes in cardiac enzyme levels and transthoracic echocardiogram coupled with Doppler tissue imaging. This resulted after ruling out many differential diagnoses. Unilateral APO secondary to functional mitral regurgitation often presents diagnostic challenges and problems of initial management for the clinician. There are multiple aetiologies of acute unilateral pulmonary oedema, namely mechanical (re-expansion), lesional, vascular, bronchial obstructions, as well as iatrogenic causes, as is the case with some lung transplantations. As with all cases of APO, the treatment is based mainly on diuretics with high-flow oxygen therapy in association with an anticoagulant, which is usually effectively combined with a platelet aggregation inhibiting drug and sometimes with vasodilators and beta-blockers. Surgical treatment with valvuloplasty or valvular replacement appears to be the most effective means for preventing relapse.

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

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...... in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p

  13. [Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

    Science.gov (United States)

    Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

    2011-09-27

    To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

  14. Magnetic resonance studies on the brain edema by the administration of the osmotic agents

    International Nuclear Information System (INIS)

    Niino, Masaki; Asakura, Tetsuhiko; Nakamura, Katsumi; Yatsushiro, Kazutaka; Kadota, Koki; Sasahira, Masahiro; Fujimoto, Toshiro; Shimooki, Susumu.

    1990-01-01

    Changes of proton relaxation times (T 1 and T 2 ) and MR imaging of the brain edema by the administration of the osmotic agents (mannitol or glycerol) were studied. Subjects were 11 patients who were composed of 4 gliomas, 2 metastatic brain tumors, 2 meningiomas, 2 hypertensive intracerebral hematomas, and a C-P angle tumor. 20% mannitol or 10% glycerol 550 ml was rapidly injected intravenously. Scanning was done before injection, just after injection, and post injection until 2 hours with passing times. We regarded the peritumoral or perihemorrahgical low density area on the CT scan as the edema, and then, relaxation times of the edema was obtained from the ROI of the calculated images corresponding to the surrounding low density area on the CT scan. The results were as follows. 1) In general, relaxation times of the edema showed a tendency to decrease after injection of the osmotic agents. Normal white matter, in the same way, showed the decreasing tendency, but the degree of the decreasing was more clearly in the edematous areas than in the white matter. 2) The changes of relaxation times did not show a uniform pattern. In most cases, relaxation times decreased just after injection. But in a few cases, relaxation times increased just after injection, transiently. In some cases, decreased relaxation times continued more than 2 hours, in the other cases, relaxation times increased at 2 hours. 3) The changes of relaxation times thought to be varied by some factors, that is --kinds of the lesions causing edema, degree of malignancy of the lesions, or phase of edema (acute or chronic) etc. 4) Osmotic agents were supposed to dehydrate the edematous lesions. In the current MR systems, there are considerably large standard deviations and inequality in the magnetic field, therefore, further investigations should be done moreover. (author)

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

    Science.gov (United States)

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

    2015-07-28

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

  16. Perinatal Hypoxic-Ischemic brain injury; MR findings

    International Nuclear Information System (INIS)

    Park, Dong Woo; Seo, Chang Hye

    1994-01-01

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

  17. Racking the brain: Detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Nicole [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G.; Gascho, Dominic [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Ruder, Thomas D. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital of Bern, Freiburgstrasse, 3010 Bern (Switzerland); Thali, Michael J. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2015-04-15

    Graphical abstract: -- Highlights: •Postmortem swelling of the brain is a typical finding on PMCT and occurs concomitant with potential antemortem or agonal brain edema. •Cerebral edema despite normal postmortem swelling is indicated by narrowed temporal horns and symmetrical herniation of the cerebral tonsils on PMCT. •Cases with intoxication or asphyxia demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units) and a ratio >1.58 between the gray and white matter. •The Hounsfield measurements of the white and gray matter help to determine the cause of death in cases of intoxication or asphyxia. -- Abstract: Purpose: The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. Materials and methods: The study collective included a total of 109 cases (n = 109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. Results: Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p < 0.001). There was a significant difference (p < 0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to

  18. Racking the brain: Detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

    International Nuclear Information System (INIS)

    Berger, Nicole; Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G.; Gascho, Dominic; Ruder, Thomas D.; Thali, Michael J.; Flach, Patricia M.

    2015-01-01

    Graphical abstract: -- Highlights: •Postmortem swelling of the brain is a typical finding on PMCT and occurs concomitant with potential antemortem or agonal brain edema. •Cerebral edema despite normal postmortem swelling is indicated by narrowed temporal horns and symmetrical herniation of the cerebral tonsils on PMCT. •Cases with intoxication or asphyxia demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units) and a ratio >1.58 between the gray and white matter. •The Hounsfield measurements of the white and gray matter help to determine the cause of death in cases of intoxication or asphyxia. -- Abstract: Purpose: The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. Materials and methods: The study collective included a total of 109 cases (n = 109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. Results: Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p < 0.001). There was a significant difference (p < 0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to

  19. Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats.   Methods: The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay.   Results: The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury.   Conclusions: It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

  20. HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

    Directory of Open Access Journals (Sweden)

    Lijun Yang

    2018-05-01

    Full Text Available Background/Aims: Traumatic brain injury (TBI is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB, subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1 has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

  1. HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model.

    Science.gov (United States)

    Yang, Lijun; Wang, Feng; Yang, Liang; Yuan, Yunchao; Chen, Yan; Zhang, Gengshen; Fan, Zhenzeng

    2018-01-01

    Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan's blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI. © 2018 The Author(s). Published by S. Karger AG, Basel.

  2. Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema.

    Science.gov (United States)

    Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

    2018-04-01

    Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

  3. Edema is not a reliable diagnostic sign to exclude small brain metastases.

    Directory of Open Access Journals (Sweden)

    Tanja Schneider

    Full Text Available No prior systematic study on the extent of vasogenic edema (VE in patients with brain metastases (BM exists. Here, we aim to determine 1 the general volumetric relationship between BM and VE, 2 a threshold diameter above which a BM shows VE, and 3 the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545, there was a statistically significant positive correlation between the volumes of the BM and the VE (P < 0.001. The optimal threshold for edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.

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

    Directory of Open Access Journals (Sweden)

    Peng Y

    2015-07-01

    Full Text Available Yihua Peng,1,* Chunhong Shao,1,* Ye Gong,2 Xuehai Wu,2 Weijun Tang,3 Shenxun Shi1 1Psychiatry Department, 2Neurosurgery Department, 3Radiology Department, Huashan Hospital, Fudan University, People’s Republic of China *These authors contributed equally to this work 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

  5. Presumptive Ischemic Brain Infarction in a Dog with Evans’ Syndrome

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    Angelo Pasquale Giannuzzi

    2014-01-01

    Full Text Available A ten-year-old neutered female mixed breed dog was referred for pale mucous membrane and acute onset of right prosencephalic clinical signs. Brain magnetic resonance imaging was suggestive for right middle cerebral artery ischemic stroke. Based on cell blood count, serum biochemistry and serologic tests and flow cytometric detection of anti-platelets and anti-red blood cells antibodies, a diagnosis of immunomediated haemolytic anemia associated with thrombocytopenia of suspected immunomediated origin was done. Immunosuppresive therapy with prednisone was started and the dog clinically recovered. Two months later complete normalization of CBC and serum biochemistry was documented. The dog remained stable for 7 months without therapy; then she relapsed. CBC revealed mild regenerative anemia with spherocytosis and thrombocytopenia. A conclusive Evans’ syndrome diagnosis was done and prednisone and cyclosporine treatment led to normalization of physical and CBC parameters. The dog is still alive at the time the paper submitted. Possible thrombotic etiopathogenetic mechanisms are illustrated in the paper and the authors suggest introducing Evans’ syndrome in the differential diagnosis list for brain ischemic stroke in dogs.

  6. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  7. NMR: its application to the experimental study of hydrocephalus and brain edema

    Energy Technology Data Exchange (ETDEWEB)

    Asato, R; Murata, T; Mori, K; Handa, H [Kyoto Univ. (Japan). Faculty of Medicine

    1981-06-01

    The pulsed NMR technique is very sensitive to molecular movement because its observation frequency is in the range of the rates of molecular movement. Furthermore it makes it possible to study the interested molecules in the biological tissues physically and noninvasively. In this report we have investigated the experimental brain edema and hydrocephalus, in both of which the tissue fluid changes are main pathology, through /sup 1/H-NMR relaxation study of water molecule in the brain tissues. The longitudinal (T/sub 1/) and the transverse (T/sub 2/) relaxation times were measured with Varian-HR-220 spectrometer modified with Nicolet-TT-100 PFT system. The experimental materials were the adult male Wister rats suffering from cold injury edema and the adult canines suffering from kaolin hydrocephalus. The study showed firstly that in brain edema no particular changes were found for relaxation times in the white matter, whereas in the gray matter, discrepancy between the changes of T/sub 1/ and T/sub 2/ was observed. That is to say, there were 2 components of T/sub 2/ in contrast with single T/sub 1/ value in the same sample of the edematous gray matter, which indicates the existence of 2 fractions of tissue water, not exchanging on an NMR time scale. Secondary, a good correlation between the longitudinal (T/sub 1/) relaxation time and the tissue water content was found for the dog brains, which suggests that we can analyse the NMR relaxation data of the dog brains based on the two-fraction fast-exchange model.

  8. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  9. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    International Nuclear Information System (INIS)

    Gang, QiangQiang; Zhang, Jianing; Hao, Peng; Xu, Yikai

    2013-01-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

  10. Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

    Directory of Open Access Journals (Sweden)

    Min Jae Kim

    2018-01-01

    Full Text Available Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4 was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg, while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1 expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

  11. Clinical and neuroradiological studies of eclampsia. Cerebral vasospasm and relation to the brain edema

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Yasuhiro; Niwa, Hisayoshi; Ando, Tetsuo; Yasuda, Takeshi; Yanagi, Tsutomu [Nagoya Daini Red Cross Hospital, Aichi (Japan)

    1995-04-01

    Clinical and neuroradiological studies involving cerebral angiography were conducted in four patients with eclampsia. In three cases (case 1, 2 and 4), neurological focal signs, abnormal low density areas on cranial CT and T{sub 2} high intensity areas on cranial MRI disappeared within a month. But in one case (case 3), cerebral infarction occurred and right hemiparesis and aphasia persisted. Cerebral angiography in the acute phase demonstrated vasospasm in all cases and arterial occlusion in the middle cerebral artery due to vasospasm in case 3. Angiography demonstrated several types of spasms, including diffuse, peripheral and multi local. Furthermore, in some cases, diffuse vasospasms were recognized at the siphon and extracranial portions of the internal carotid artery. In one case (Case 4), segmental vasospasms were detected in the bilateral vertebral arteries. Three to four weeks later, follow-up cerebral angiography was performed in three cases. Cerebral vasospasms had partially or completely recovered. Subarachnoid hemorrhage (SAH) was excluded by lumbar puncture and neuroradiological findings in all cases. We concluded that eclampsia itself causes cerebral vasospasm and that the mechanism of vasospasm is different from that of SAH, since cerebral vasospasm occurred in the extracranial cerebral arteries. We suspected that cerebral vasospasm in eclampsia causes cerebral ischemia, which leads to cytotoxic edema and dysfunction of the blood-brain barrier (BBB) and cerebral autoregulation. With this background, brain edema, especially vasogenic edema, may easily occur and clinical symptoms of eclampsia may appear when the blood pressure rapidly increases. (author).

  12. Clinical and neuroradiological studies of eclampsia. Cerebral vasospasm and relation to the brain edema

    International Nuclear Information System (INIS)

    Ito, Yasuhiro; Niwa, Hisayoshi; Ando, Tetsuo; Yasuda, Takeshi; Yanagi, Tsutomu

    1995-01-01

    Clinical and neuroradiological studies involving cerebral angiography were conducted in four patients with eclampsia. In three cases (case 1, 2 and 4), neurological focal signs, abnormal low density areas on cranial CT and T 2 high intensity areas on cranial MRI disappeared within a month. But in one case (case 3), cerebral infarction occurred and right hemiparesis and aphasia persisted. Cerebral angiography in the acute phase demonstrated vasospasm in all cases and arterial occlusion in the middle cerebral artery due to vasospasm in case 3. Angiography demonstrated several types of spasms, including diffuse, peripheral and multi local. Furthermore, in some cases, diffuse vasospasms were recognized at the siphon and extracranial portions of the internal carotid artery. In one case (Case 4), segmental vasospasms were detected in the bilateral vertebral arteries. Three to four weeks later, follow-up cerebral angiography was performed in three cases. Cerebral vasospasms had partially or completely recovered. Subarachnoid hemorrhage (SAH) was excluded by lumbar puncture and neuroradiological findings in all cases. We concluded that eclampsia itself causes cerebral vasospasm and that the mechanism of vasospasm is different from that of SAH, since cerebral vasospasm occurred in the extracranial cerebral arteries. We suspected that cerebral vasospasm in eclampsia causes cerebral ischemia, which leads to cytotoxic edema and dysfunction of the blood-brain barrier (BBB) and cerebral autoregulation. With this background, brain edema, especially vasogenic edema, may easily occur and clinical symptoms of eclampsia may appear when the blood pressure rapidly increases. (author)

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

    Directory of Open Access Journals (Sweden)

    Sayyed Gholam Reza Mortazavimoghaddam

    2012-01-01

    Full Text Available 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.

  14. Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger

    2016-01-01

    of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain......Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...

  15. Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

    Science.gov (United States)

    Doi, Kazuhisa; Kawano, Takeshi; Morioka, Yujiro; Fujita, Yasutaka; Nishimura, Masuhiro

    2006-12-01

    This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

  16. AQP4 expression and its relationship with brain edema after gamma kife radiosurgery in rats

    International Nuclear Information System (INIS)

    Shen Guangjian; Xu Minhui; Zou Yongwen; Gen Mingying; Li Feipeng; Tang Wenyuan; Sun Shanquan

    2007-01-01

    Objective: To explore AQP4 expression and its relationship with brain edema after gamma knife radiosurgery (GKRS) in rats. Methods: Wistar rats were divided into two groups-the control group and experimental group. The experimental group model was established by radiating rat left rotral caudate nucleus with GKRS (100 Gy, 4 mm), and was examinded at interval times of 1 d, 3 d, 7 d, 15 d, 30 d and 45 d. Brain water content (BWC) was determined by wet-dry weighing method. AQP4 expression on mRNA and protein were measured by immunohistochemistry (ICH) and in situ hybridization (ISH). Results: In control group, AQP4 protein and its mRNA were expressed in subpial astrocytes, choroid plexus, ependyma and perivascular astrocytes. After GKRS, AQP4 protein and its mRNA in these sites were enhanced, and became most remarkable at 30 d. The positive corrlationship was showed between AQP4 and its mRNA, and AQP4 and BWC. Conclusions: AQP4 protein and its mRNA can be induced in some brain zone after irradiating rat left rotral caudate nucleus with GKRS. The increased expression of AQP4 and its mRNA may play a role in the ocurrence or development of brain edema after GKRS. (authors)

  17. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1

    Directory of Open Access Journals (Sweden)

    Jingchun Guo

    2012-07-01

    Full Text Available Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1 protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

  18. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema: Correlation with variation in apparent diffusion coefficient.

    Science.gov (United States)

    Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong

    2012-07-25

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

  19. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury

    OpenAIRE

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-01-01

    Abstract Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET). We consecutively enrolled 11 patients with FOG after HIBI. The patients’ overall brain metabolism was measured by F-18 FDG PET, and we co...

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

    Science.gov (United States)

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

    2015-10-01

    To investigate the risks and pattern of evolution of peritumoral brain edema (PTE) after stereotactic radiosurgery (SRS) for asymptomatic intracranial meningiomas. 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. 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 (pmaking 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.

  1. Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

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    Lefebvre Nicolas

    2007-05-01

    Full Text Available Background Hypersentivity Syndrome (HS may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature. Case presentation A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months. Conclusion Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.

  2. Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

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    van Straaten Elisabeth CW

    2012-07-01

    Full Text Available Abstract Background White matter hyperintensities (WMH can lead to dementia but the underlying physiological mechanisms are unclear. We compared relative oscillatory power from electroencephalographic studies (EEGs of 17 patients with subcortical ischemic vascular dementia, based on extensive white matter hyperintensities (SIVD-WMH with 17 controls to investigate physiological changes underlying this diagnosis. Results Differences between the groups were large, with a decrease of relative power of fast activity in patients (alpha power 0.25 ± 0.12 versus 0.38 ± 0.13, p = 0.01; beta power 0.08 ± 0.04 versus 0.19 ± 0.07; p Conclusions This pattern of disturbance in oscillatory brain activity indicate loss of connections between neurons, providing a first step in the understanding of cognitive dysfunction in SIVD-WMH.

  3. Effect of Conbercept injection and macular grid pattern photocoagulation in treating macular edema after non-ischemic branch retinal vein occlusion

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    Jiang Zhu

    2018-06-01

    Full Text Available AIM: To investigate the effects and safety of intravitreal injection of Conbercept combined with macular grid pattern photocoagulation for macular edema secondary to non-ischemic branch retinal vein occlusion(BRVO. METHODS: A total of 38 patients(38 eyes with macular edema following non-ischemic BRVO were retrospectively analyzed. All patients were given best corrected visual acuity(BCVA, intraocular pressure, slit lamp with preset lens, optic coherent tomography(OCTand fluorescence fundus angiography(FFAexamination. The BCVA and central macular thickness(CMTwere observed before and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment. The change in pre-treatment and post-treatment were compared, and the related complications were recorded. RESULTS:BCVA before treatment and 1wk, 1, 2, 3, 6, 9 and 12mo after treatment were 0.89±0.62, 0.64±0.59, 0.55±0.62, 0.46±0.43, 0.53±0.67, 0.43±0.38, 0.42±0.29, 0.40±0.30, the difference was statistically significant between that before and after treatment(PP>0.05. CMT were 683.25±236.47, 298.65±116.12, 276.89±107.28, 281.55±99.62, 251.41±119.47, 240.58±88.62, 231.74±75.36, 209.51±84.68μm, the difference was statistically significant between that before and after treatment(PP>0.05. There were 11 eyes received one injection, 18 eyes with two injections, 2 eyes with 3, 3 eyes with 4, and 4 eyes more than 4, the average injection was 2.01±1.42. The CMT decreased after every injection. The intraocular hypertension and other complications were not seen after treatment. CONCLUSION: Intravitreal injection of conbercept combined with macular grid pattern photocoagulation for macular edema to non-ischemic BRVO can reduce the macular edema and improve BCVA, which is effective and safety.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Xie, J; Qian, Z; Li, W; Hu, G [Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, 29 Yudao Street, Nanjing 210016 (China); Yang, T, E-mail: zhiyu@nuaa.edu.cn [School of Clinical Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China)

    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 ({mu}{sub s}') and BWC. By recording {mu}{sub 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.

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

    International Nuclear Information System (INIS)

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

    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 (μ s ') and BWC. By recording μ 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.

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

    Science.gov (United States)

    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.

  10. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    Science.gov (United States)

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  11. The significance of morphological changes in the brain-tumor interface for the pathogenesis of brain edema in meningioma: Magnetic resonance tomography and intraoperative findings

    International Nuclear Information System (INIS)

    Bitzer, M.; Klose, U.; Naegele, T.; Mundinger, P.; Voigt, K.; Freudenstein, D.; Heiss, E.

    1999-01-01

    Purpose: The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. Methods: 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness=2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: Direct contact between tumor and white matter, 3: Tumor infiltration into brain. Results: Edema-associated meningiomas showed a significantly (p=0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema. Conclusions: Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas. (orig.) [de

  12. Acute dimethyl sulfoxide therapy in brain edema. Part 3: effect of a 3-hour infusion.

    Science.gov (United States)

    Del Bigio, M; James, H E; Camp, P E; Werner, R; Marshall, L F; Tung, H

    1982-01-01

    Albino rabbits with experimental brain edema produced by a combined cryogenic left hemisphere lesion and metabolic 6-aminonicotinamide lesion were administered a 3-hour intravenous infusion of dimethyl sulfoxide (DMSO). Simultaneous recording of intracranial pressure (ICP), systolic arterial pressure (SAP), and central venous pressure (CVP) and electroencephalography were performed while the animals were being ventilated mechanically to produce a constant Pa CO2 value (38-42 torr). At the end of the infusion, the brain water and electrolyte contents were measured. There was a persistent and progressive reduction of ICP during the infusion, the nadir occurring at 3 hours (p less than 0.005 from zero time), with no change in SAP or CVP. There was a reduction of brain water in both hemispheres when compared to untreated controls, but this was significant for the right hemisphere only (p less than 0.005). There was a significant reduction of the brain sodium content for both hemispheres, but no significant change occurred in brain potassium content. The DMSO infusion was effective not only in reducing ICP, but also in sustaining this reduction for 3 hours.

  13. Quantitative analysis of computed tomography images and early detection of cerebral edema for pediatric traumatic brain injury patients: retrospective study.

    Science.gov (United States)

    Kim, Hakseung; Kim, Gwang-dong; Yoon, Byung C; Kim, Keewon; Kim, Byung-Jo; Choi, Young Hun; Czosnyka, Marek; Oh, Byung-Mo; Kim, Dong-Joo

    2014-10-22

    The purpose of this study was to identify whether the distribution of Hounsfield Unit (HU) values across the intracranial area in computed tomography (CT) images can be used as an effective diagnostic tool for determining the severity of cerebral edema in pediatric traumatic brain injury (TBI) patients. CT images, medical records and radiology reports on 70 pediatric patients were collected. Based on radiology reports and the Marshall classification, the patients were grouped as mild edema patients (n=37) or severe edema patients (n=33). Automated quantitative analysis using unenhanced CT images was applied to eliminate artifacts and identify the difference in HU value distribution across the intracranial area between these groups. The proportion of pixels with HU=17 to 24 was highly correlated with the existence of severe cerebral edema (P<0.01). This proportion was also able to differentiate patients who developed delayed cerebral edema from mild TBI patients. A significant difference between deceased patients and surviving patients in terms of the HU distribution came from the proportion of pixels with HU=19 to HU=23 (P<0.01). The proportion of pixels with an HU value of 17 to 24 in the entire cerebral area of a non-enhanced CT image can be an effective basis for evaluating the severity of cerebral edema. Based on this result, we propose a novel approach for the early detection of severe cerebral edema.

  14. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. The distribution of N-isopropyl-p-iodoamphetamine in experimental ischemic brain of the mongolian gerbil

    International Nuclear Information System (INIS)

    Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

    1988-01-01

    We studied the distribution of N-isopropyl-p-[I-131]-iodoamphetamine (IMP) in permanent and temporary ischemic brains of mongolian gerbils. For the permanent ischemic brain model, the right common carotid artery was ligated under ether anesthesia. For the temporary ischemic brain model, the right common carotid artery was clamped by a clip and recirculated at 3 hours thereafter. After given time intervals, 1.35 MBq (50 μCi) of IMP was injected intravenously into 17 gerbils (permanent ischemic brain model), 18 gerbils (temporary ischemic brain model) which had severe neurological symptoms, and 3 normal gerbils for controls. One minute, 10 minutes, 1 hour and 6 hours after the injection, gerbils were sacrified and autoradiography of the brain was performed. The activity of IMP in various parts of the brain was calculated from each autoradiogram. In permanent ischemic brains, low perfusion areas were observed in the right cerebral hemisphere, the brain stem (5 ∼ 20 % of normal value), and in the left hemisphere (40 ∼ 60 % of normal value). In temporary ischemic brains, focal areas of increased activity were observed in the right cerebral hemisphere and the thalamus from 10 minutes to 24 hours after recirculation. The high activity disappeared rapidly at 10 minutes after the injection. It seemed that this high activity represented luxury perfusion in the region with severe tissue damage. In the left hemisphere, almost complete recovery of perfusion occurred at 1 ∼ 3 days after recirculation. These results suggested the possibility of IMP to demonstrate cerebral ischemia, luxury perfusion and diaschisis. (author)

  16. Brain Edema and Neurologic Deficits in Rat Stroke Model: The Effect of Hydroalcoholic Extract of Salvia Officinalis

    Directory of Open Access Journals (Sweden)

    elham ghasemloo

    2015-11-01

    Full Text Available Bachground & Objectives: In the brain ischemia, the production of free radicals increases. Salvia is a rich source of antioxidant compounds; therefore, in this study we will examine the effects of Salvia extracts on brain edema and score of neurological deficits.  Materials & Methods: In this experimental study, 35 male Wistar rats were randomly divided into 5 groups, each containing 7 rats. The control group received distilled water, and the other three groups received intrapertioneally hydroalcoholic extracts of Salvia officinalis with dosages of 50, 75, and 100 mg/kg for 3 weeks (1+3=4, Where is the other group? There should be five groups but there are only four groups here.. Thereafter, each main group underwent 60 min middle cerebral artery occlusion 2 hours after the last injection of Salvia extracts .This occlusion caused ischemia in the right hemisphere. Then, the brain edema was assessed, and the neurologic deficits were analyzed. The sham group was not treated and no induction of brain ischemia. Brain edema was analyzed through SPSS18 software and LSD method, while the analysis of neurologic deficits was carried out by Mann-Whitney U. Results: Our study results indicate that the hydroalcoholic extracts of Salvia reduced permeability brain edema in three dosages of 50, 75, and 100mg/kg (83/29±0/42 , 82/10±0/32 and 81/29±0/48, respectively compared with the control group (85/31±0/58. They also reduced the neurologic deficits in experimental groups of 75 and 100 mg/kg (1/43±0/37 and 1±0/31, respectively compared with the control group (3/71±0/42 (p<0.05. Conclusion: Salvia officinalis apparently have a protective effect against stroke damage due to the reduced brain edema and neurological disorders.

  17. Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Hansen, Morten Bagge

    2018-01-01

    clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16......), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal.......555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION: This study does not provide any support for unselective...

  18. Serum Markers of Apoptosis in Traumatic and Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    N. N. Yepifantseva

    2009-01-01

    Full Text Available Objective: to study the time course of changes and relationship of the serum indicators of apoptotic processes in neurore-suscitation patients. Subjects and methods. Thirty-eight neuroresuscitation patients, including 14 patients with severe brain injury (SBI (mean age 41.4±4.3 years and 24 patients with strokes (mean age 53.8±2.5 years, were examined. The group of patients with strokes was divided into 2 subroups: 1 11 patients with ischemic strokes (IS and 2 13 with hemorrhagic strokes (HS. The Glasgow coma scores for admission consciousness loss were 7.6±0.8 in the SBI group and 9.5±0.7 in the stroke group; mortality was 28.6 and 37.5%, respectively. A control group included 16 subjects (mean age 47.9±3.8 years. The investigators measured the serum levels of FAS antigen and its ligand (sAPO-I/FAS and sFAS-L, cas-pase-1/ICE, sCD40 (Bender MedSystem, Austria and hTRAIL (Biosource, Belgium by solid-phase immunoassay in neuroresuscitation patients on days 1, 7, and 14 of the acute period of diseases. They used statistical methods, such as Wilcoxon-Mann-Whitney U-test, Spearman’s rank correlation test. Results. A reduction in hTRAIL was observed in all the groups. There was a decrease in serum sCD40 in strokes on days 1 to 14 and in SBI on days 7 to 14. An increase in caspase 1/ICE was seen in HS in the first 24 hours, in IS on days 1 to 7, and in SBI on days 1 to 14. The most pronounced rise in caspase-1/ICE was induced by ischemic brain lesion within the first week of disease. A prolonged increase up to 2 weeks was noted in SBI. No rise in serum FAS-L was found in the examinees. The time course of changes in sAPO-I/FAS was different in all the groups. The most marked, moderate, and none reductions were revealed in HS, IS, and SBI, respectively. There was a pronounced serum sAPO-I/FAS increase in SBI within the first 24 hours. Assessment of correlations between the serum indicators of apoptosis revealed that there were differences in the

  19. The effect of steroids on experimental brain edema induced by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, M [Kobe Univ. (Japan). School of Medicine; Kakei, M

    1975-04-01

    In order to study the effect of steroids on brain edema, complicated by radiotherapy to brain tumors, an experiment was carried out in rats. Five thousand rads of cobalt-60 were irradiated to the head only of a rat, and 20 mg/kg of water-soluble prednine was given intraperitoneally. A single administration of the whole dose increased the amount of brain fluid to 79.35 +- 0.30 g/ 100 g wet wt.. This value was not significantly different from that of the rat which had received only the 5,000 rad irradiation. In a rat which received prednine in 6 divided doses at intervals of 4 hours, the fluid amount reached 78.33 +- 0.52 g/ 100 g wet wt. and was clearly lower than that of the rat which had been irradiated only, 79.51 +- 0.23 g/ 100 g wet wt. neither was the value significantly different from that of a normal rat which had not been exposed 78.72 +- 0.82 g/ 100 g wet wt.. Therefore, fractional administration of prednine was demonstrated to be effective.

  20. Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois; Ferger, Boris; Beer, Ronny; Sohm, Florian; Broessner, Gregor; Hackl, Werner; Rhomberg, Paul; Lackner, Peter; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2015-12-01

    Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting. We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects. CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p taurine levels compared to those without (Wald = 7.3, df = 1, p taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.

  1. Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4.

    Directory of Open Access Journals (Sweden)

    Heling Chu

    Full Text Available Vascular endothelial growth factor (VEGF has protective effects on many neurological diseases. However, whether VEGF acts on brain edema following intracerebral hemorrhage (ICH is largely unknown. Our previous study has shown aquaporin-4 (AQP4 plays an important role in brain edema elimination following ICH. Meanwhile, there is close relationship between VEGF and AQP4. In this study, we aimed to test effects of VEGF on brain edema following ICH and examine whether they were AQP4 dependent. Recombinant human VEGF165 (rhVEGF165 was injected intracerebroventricularly 1 d after ICH induced by microinjecting autologous whole blood into striatum. We detected perihemotomal AQP4 protein expression, then examined the effects of rhVEGF165 on perihemotomal brain edema at 1 d, 3 d, and 7 d after injection in wild type (AQP4(+/+ and AQP4 knock-out (AQP4(-/- mice. Furthermore, we assessed the possible signal transduction pathways activated by VEGF to regulate AQP4 expression via astrocyte cultures. We found perihemotomal AQP4 protein expression was highly increased by rhVEGF165. RhVEGF165 alleviated perihemotomal brain edema in AQP4(+/+ mice at each time point, but had no effect on AQP4(-/- mice. Perihemotomal EB extravasation was increased by rhVEGF165 in AQP4(-/- mice, but not AQP4(+/+ mice. RhVEGF165 reduced neurological deficits and increased Nissl's staining cells surrounding hemotoma in both types of mice and these effects were related to AQP4. RhVEGF165 up-regulated phospharylation of C-Jun amino-terminal kinase (p-JNK and extracellular signal-regulated kinase (p-ERK and AQP4 protein in cultured astrocytes. The latter was inhibited by JNK and ERK inhibitors. In conclusion, VEGF reduces neurological deficits, brain edema, and neuronal death surrounding hemotoma but has no influence on BBB permeability. These effects are closely related to AQP4 up-regulation, possibly through activating JNK and ERK pathways. The current study may present new insights to

  2. Nuclear magnetic resonance studies on brain edema. Time course of /sup 1/H-NMR relaxation times

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    Naruse, S; Horikawa, Y; Tanaka, C; Hirakawa, K; Nishikawa, H [Kyoto Prefectural Univ. of Medicine (Japan)

    1981-06-01

    1. The state of water in normal and edematous brain tissue was studied by measurement of proton longitudinal (T/sub 1/) and transverse (T/sub 2/) relaxation times using pulsed nuclear magnetic resonance (NMR) technique. 2. In control rats, T/sub 1/ and T/sub 2/ of water showed one component, which was more fast in white matter. Those values displayed 1.07 - 1.18 sec. of T/sub 1/ and 75 - 76 msec. of T/sub 2/. 3. When rat brain was injured by cold, T/sub 1/ was observed to become longer (1.18 - 1.27 sec.), and T/sub 2/ was observed be separated into two components, the faster T/sub 2/ (45 - 50 msec.) and slower T/sub 2/ (100 - 105 msec.), in both gray and white matter of the injured side. 4. In triethyltin (TET) induced brain edema, elongation of T/sub 1/ (1.2 sec.) and remarkable separation of T/sub 2/, faster T/sub 2/ (75 msec.) and slower T/sub 2/ (400 - 450 msec.), were observed in white matter. 5. In both cold and TET induced edema, slower T/sub 2/ fraction is suggested to be the extracellular space and faster T/sub 2/ fraction, intracellular. 6. T/sub 2/ changes precede the water content changes in cold injury, and parallel in TET induced edema. Those changes of relaxation times are reversible. 7. T/sub 2/ changes of water is more sensitive than the T/sub 1/ for the detection of production and disappearance of brain edema. 8. These results disclose the dynamic movements of water during the course of brain edema and offered significant information of the clinical application of NMR-CT.

  3. Studies on improvement of diagnosis of neurosurgical lesions by computed tomography, 2. On low-density findings in brain tumors and those in brain edema particularly

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, T [Gifu Univ. (Japan). Faculty of Medicine

    1980-09-01

    CT findings of low-density in brain tumor cases were classified into the following 2 groups. (a) low-density lesions within brain tumor, masses. (b) low-density lesions surrounding brain tumors. Group (a) represented either fluid-containing cysts, necrotic masses or low-density tumor parenchyme, as confirmed by operative findings. it was impossible to diagnose pathological nature of low-density lesions merely by analyzing their Hounsfield No. (H-No.), excepting epidermoid, teratoma and arachnoid cyst, in which H-No. was essential for diagnosis. Group (b) was classified into 4 subgroups (grade 0 to III) by modifying Kazner's CT classification of brain edema. In most of malignant tumors (such as glioblastomas, metastatic tumors), wide peritumoral low-density lesions were observed. For example, peritumoral low-density lesions of grade III or II were observed in 87% of glioblastoma cases. But, peritumoral low-density lesions of grade II or III were observed also in benign tumor cases, i.e. in 50% of meningioma cases. In a case of astrocytoma, it was impossible to detect the border of the tumor and perifocal edema, even by means of contrast enhancement. It was confirmed by operative findings, that peritumoral low-density lesions could be caused not only brain edema, but also by enlarged peritumoral subarachnoid space or brain demyelinization due to compression by the tumor. In clinical cases, showing brain edema by CT, and in dogs, in which brain edema was produced by cold injury, the author observed that mean values of H-No. in the region of interest on the lesion side significantly increased after intravenous administration of 10% glycerol solution. It was considered that the observed increase in H-No. was caused by dehydration of the edematous brain and increase in regional cerebral blood volume.

  4. Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

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    Vida Naderi

    2015-02-01

    Full Text Available 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-α antagonist (MPP and, ER-β 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

  5. NF-κB in The Mechanism of Brain Edema in Acute Liver Failure: Studies in Transgenic Mice

    Science.gov (United States)

    Jayakumar, A.R.; Bethea, J.R.; Tong, X.Y.; Gomez, J.; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling and brain edema are major complications of the acute form of hepatic encephalopathy (acute liver failure, ALF). While elevated brain ammonia level is a well-known etiological factor in ALF, the mechanism by which ammonia brings about astrocyte swelling is not well understood. We recently found that astrocyte cultures exposed to ammonia activated nuclear factor-kappaB (NF-κB), and that pharmacological inhibition of such activation led to a reduction in astrocyte swelling. Although these findings suggest the involvement of NF-κB in astrocyte swelling in vitro, it is not known whether NF-κB contributes to the development of brain edema in ALF in vivo. Furthermore, pharmacological agents used to inhibit NF-κB may have non-specific effects. Accordingly, we used transgenic (Tg) mice that have a functional inactivation of astrocytic NF-κB and examined whether these mice are resistant to ALF-associated brain edema. ALF was induced in mice by treatment with the hepatotoxin thioacetamide (TAA). Wild type (WT) mice treated with TAA showed a significant increase in brain water content (1.65%) along with prominent astrocyte swelling and spongiosis of the neuropil, consistent with the presence of cytotoxic edema. These changes were not observed in Tg mice treated with TAA. Additionally, WT mice with ALF showed an increase in inducible nitric oxide synthase (iNOS) immunoreactivity in astrocytes from WT mice treated with TAA (iNOS is known to be activated by NF-κB and to contribute to cell swelling). By contrast, Tg mice treated with TAA did not exhibit brain edema, histological changes nor an increase in iNOS immunoreactivity. We also examined astrocytes cultures derived from Tg mice to determine whether these cells exhibit a lesser degree of swelling and cytopathological changes following exposure to ammonia. Astrocyte cultures derived from Tg mice showed no cell swelling nor morphological abnormalities when exposed to ammonia for 24 h. By contrast

  6. Magnetic resonance studies on the brain edema by the administration of the osmotic agents; Special references to the relaxation times

    Energy Technology Data Exchange (ETDEWEB)

    Niino, Masaki; Asakura, Tetsuhiko; Nakamura, Katsumi; Yatsushiro, Kazutaka; Kadota, Koki (Kagoshima Univ. (Japan). Faculty of Medicine); Sasahira, Masahiro; Fujimoto, Toshiro; Shimooki, Susumu

    1990-03-01

    Changes of proton relaxation times (T{sub 1} and T{sub 2}) and MR imaging of the brain edema by the administration of the osmotic agents (mannitol or glycerol) were studied. Subjects were 11 patients who were composed of 4 gliomas, 2 metastatic brain tumors, 2 meningiomas, 2 hypertensive intracerebral hematomas, and a C-P angle tumor. 20% mannitol or 10% glycerol 550 ml was rapidly injected intravenously. Scanning was done before injection, just after injection, and post injection until 2 hours with passing times. We regarded the peritumoral or perihemorrahgical low density area on the CT scan as the edema, and then, relaxation times of the edema was obtained from the ROI of the calculated images corresponding to the surrounding low density area on the CT scan. The results were as follows. (1) In general, relaxation times of the edema showed a tendency to decrease after injection of the osmotic agents. Normal white matter, in the same way, showed the decreasing tendency, but the degree of the decreasing was more clearly in the edematous areas than in the white matter. (2) The changes of relaxation times did not show a uniform pattern. In most cases, relaxation times decreased just after injection. But in a few cases, relaxation times increased just after injection, transiently. In some cases, decreased relaxation times continued more than 2 hours, in the other cases, relaxation times increased at 2 hours. (3) The changes of relaxation times thought to be varied by some factors, that is --kinds of the lesions causing edema, degree of malignancy of the lesions, or phase of edema (acute or chronic) etc. (4) Osmotic agents were supposed to dehydrate the edematous lesions. In the current MR systems, there are considerably large standard deviations and inequality in the magnetic field, therefore, further investigations should be done moreover. (author).

  7. Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke

    Science.gov (United States)

    Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M

    2013-01-01

    Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281

  8. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Shelly A Cruz

    2018-01-01

    Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

  9. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

    Science.gov (United States)

    Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

    2004-09-15

    Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

  10. Relationship between alternation of cerebral blood flow and formation of brain edema around the hematoma after experimental intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Zhou Jian; Gao Peiyi; Li Xiaoguang

    2005-01-01

    Objective: To investigate the mechanism of brain edema formation around the hematoma and the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage (ICH) in rats, and to provide experimental basis for the clinical treatment of ICH . Methods: Seventy male Sprague-Dawley rats were randomly divided into ICH groups and sham-operated groups. ICH was produced by microinjection of 40 ul fresh autologous blood or saline into the right caudatum. Dynamic CT perfusion imaging was performed, and the parameters of regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and mean transit time (MTT) around the hematoma were calculated respectively. Then the rats were sacrificed, and the water content, sodium, potassium, and calcium concentrations were measured respectively. The correlative study between the water content and rCBF and rCBV were carried out. Results:The gradient of perihematomal hypoperfusion was revealed on CT perfusion maps in ICH groups. The alternation of rCBF around the hematomas were fluctuated, and rCBF reduction was most pronounced at 1 hour afer ICH, then the rCBF gradually returned, reaching the peaks at 6 hours and 24 hours after ICH, respectively. In the meantime, rCBV reduction around the hematoma was most pronounced at 1 hour after ICH. Then the rCBV gradually increased, and reaching the peak at 24 hours. The water contents were gradually increased in the ipsilateral basal ganglia in the animals sacrificed at 6, 24, and 72 hours. The accumulation of water was at its peak at 24 hours, and remained in the animals sacrificed at the 72 hours. The perihemorrhagic water contents correlated significantly with rCBV surrounding hematomas, r=0.372 (one-tailed), P<0.05. Conclusion: The perihemorrhagic brain edema results from the common effects of the blood-brain-barrier disruption, cytotoxic edema, and the accumulation of osmotically active substances. The r

  11. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    Science.gov (United States)

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

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    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  13. Quantitative analysis of computed tomography images and early detection of cerebral edema for pediatric traumatic brain injury patients: retrospective study

    OpenAIRE

    Kim, Hakseung; Kim, Gwang-dong; Yoon, Byung C; Kim, Keewon; Kim, Byung-Jo; Choi, Young Hun; Czosnyka, Marek; Oh, Byung-Mo; Kim, Dong-Joo

    2014-01-01

    Background The purpose of this study was to identify whether the distribution of Hounsfield Unit (HU) values across the intracranial area in computed tomography (CT) images can be used as an effective diagnostic tool for determining the severity of cerebral edema in pediatric traumatic brain injury (TBI) patients. Methods CT images, medical records and radiology reports on 70 pediatric patients were collected. Based on radiology reports and the Marshall classification, the patients were group...

  14. Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion. The Funagata study

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Tamotsu; Daimon, Makoto; Eguchi, Hideyuki; Hosoya, Takaaki; Kawanami, Toru; Kurita, Keiji; Tominaga, Makoto; Kato, Takeo [Yamagata Univ. (Japan). School of Medicine

    2002-05-01

    The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3{+-}0.8 years) and 45 with long duration (long DM; 8.9{+-}5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion. (author)

  15. Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion. The Funagata study

    International Nuclear Information System (INIS)

    Saitoh, Tamotsu; Daimon, Makoto; Eguchi, Hideyuki; Hosoya, Takaaki; Kawanami, Toru; Kurita, Keiji; Tominaga, Makoto; Kato, Takeo

    2002-01-01

    The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3±0.8 years) and 45 with long duration (long DM; 8.9±5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion. (author)

  16. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM-Mediated Protection of Ischemic Brain.

    Directory of Open Access Journals (Sweden)

    Chi-Hsin Lin

    Full Text Available The protective value of neuron-derived conditioned medium (NCM in cerebral ischemia and the underlying mechanism(s responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO animal model, we discovered that ischemia/reperfusion (I/R-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  17. Edaravone Enhances Brain-Derived Neurotrophic Factor Production in the Ischemic Mouse Brain

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    Satoshi Okuyama

    2015-04-01

    Full Text Available Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1 accelerated increases in the production of brain-derived neurotrophic factor (BDNF in the hippocampus; (2 increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3 suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4 induced the phosphorylation of cAMP response element-binding (CREB, a transcription factor that regulates BDNF gene expression; and (5 induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.

  18. Computed tomography and brain scintigraphy in ischemic stroke

    International Nuclear Information System (INIS)

    Chiu, L.C.; Fodor, L.B.; Cornell, S.H.; Christie, J.H.

    1976-01-01

    Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this sign should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases

  19. Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

    International Nuclear Information System (INIS)

    Toh, Cheng-Hong; Wong, Alex M.-C; Wong, Ho-Fai; Wan, Yung-Liang; Wei, Kuo-Chen; Ng, Shu-Hang

    2007-01-01

    We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P -3 mm 2 /s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 ± 0.057 and 0.820 ± 0.094, the mean MD ratios were 220.3 ± 22.6 and 193.1 ± 23.4, the mean FA values were 0.146 ± 0.026 and 0.199 ± 0.052, and the mean FA ratios were 32.3 ± 5.9 and 46.0 ± 12.1. All the values were significantly different between metastases and meningiomas (MD values P 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging. (orig.)

  20. Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Toh, Cheng-Hong; Wong, Alex M.-C; Wong, Ho-Fai; Wan, Yung-Liang [Chang Gung Memorial Hospital, Department of Medical Imaging and Intervention, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Wei, Kuo-Chen [Chang Gung Memorial Hospital, Department of Neurosurgery, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Ng, Shu-Hang [Chang Gung Memorial Hospital, Department of Medical Imaging and Intervention, Tao-Yuan (China); Chang Gung University, School of Medicine and Medical Technology, Tao-Yuan (China); Chang Gung Memorial Hospital, Molecular Image Center, Tao-Yuan (China)

    2007-06-15

    We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P < 0.05 was taken as indicating statistical significance. The mean MD values (x 10{sup -3} mm{sup 2}/s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 {+-} 0.057 and 0.820 {+-} 0.094, the mean MD ratios were 220.3 {+-} 22.6 and 193.1 {+-} 23.4, the mean FA values were 0.146 {+-} 0.026 and 0.199 {+-} 0.052, and the mean FA ratios were 32.3 {+-} 5.9 and 46.0 {+-} 12.1. All the values were significantly different between metastases and meningiomas (MD values P = 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging. (orig.)

  1. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Harford-Wright

    Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

  2. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Inflammation, caffeine and adenosine in neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max

    2014-01-01

    Background: Brain injury during the neonatal period has potentially lifelong consequences for a child. Perinatal infections and inflammation can induce preterm birth and unfavorable cognitive development, Thus inflammation has received enthusiastic interest for potential therapeutic approaches seeking to protect the newborn brain. Experimental evidence demonstrates that inflammation induces brain injury succeeding the initial insult. A key cytokine in brain injury is the tumor necrosis factor...

  4. Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain

    OpenAIRE

    Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua

    2012-01-01

    Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in ...

  5. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

    2015-01-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

  6. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  7. Effect of steroid on brain tumors and surround edemas : observation with regional cerebral blood volume (rCBV) maps of perfusion MRI

    International Nuclear Information System (INIS)

    Choi, Ju Youl; Sun, Joo Sung; Kim, Sun Yong; Kim, Ji Hyung; Suh, Jung Ho; Cho, Kyung Gi; Kim, Jang Sung

    2000-01-01

    To observe the hemodynamic change in brain tumors and peritumoral edemas after steroid treatment, and then investigate the clinical usefulness of perfusion MRI. We acquired conventional and perfusion MR images in 15 patients with various intracranial tumors (4 glioblastoma multiformes, 4 meningiomas, 3 metastatic tumors, 1 anaplastic ependymoma, 1 anaplastic astrocytoma, 1 hemangioblastoma, and 1 pilocytic astrocytoma). For perfusion MR imaging, a 1.5T unit employing the gradient-echo EPI technique was used, and further perfusion MR images were obtained 2-10 days after intravenous steroid therapy. After processing of the raw data, regional cerebral blood volume (rCBV) maps were reconstructed. The maps were visually evaluated by comparing relative perfusion in brain tumors and peritumoral edemas with that in contralateral white matter. Objective evaluations were performed by comparing the perfusion ratios of brain tumors and peritumoral edemas. Visual evaluations of rCBV maps, showed that in most brain tumors (67%, 10/15), perfusion was high before steroid treatment and showed in (80%, 12/15) decreased afterwards. Objective evaluation, showed that in all brain tumors, perfusion decreased. Visual evaluation of perfusion change in peritumoral edemas revealed change in only one case, but objective evaluation indicated that perfusion decreased significantly in all seven cases. rCBV maps acquired by perfusion MR imaging can provide hemodynamic information about brain tumors and peritumoral edemas. Such maps could prove helpful in the preoperative planning of brain tumor surgery and the monitoring of steroid effects during conservative treatment. (author)

  8. Dietary Virgin Olive Oil Reduces Blood Brain Barrier Permeability, Brain Edema, and Brain Injury in Rats Subjected to Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Fatemeh Mohagheghi

    2010-01-01

    Full Text Available Recent studies suggest that dietary virgin olive oil (VOO reduces hypoxia-reoxygenation injury in rat brain slices. We sought to extend these observations in an in vivo study of rat cerebral ischemia-reperfusion injury. Four groups, each consisting of 18 Wistar rats, were studied. One group (control received saline, while three treatment groups received oral VOO (0.25, 0.5, and 0.75 mL/kg/day, respectively. After 30 days, blood lipid profiles were determined, before a 60-min period of middle cerebral artery occlusion (MCAO. After 24-h reperfusion, neurological deficit scores, infarct volume, brain edema, and blood brain barrier permeability were each assessed in subgroups of six animals drawn from each main group. VOO reduced the LDL/HDL ratio in doses of 0.25, 0.5, and 0.75 mL/kg/day in comparison to the control group (p < 0.05, and offered cerebroprotection from ischemia-reperfusion. For controls vs. doses of 0.25 vs. 0.5 vs. 0.75 mL/kg/day, attenuated corrected infarct volumes were 207.82 ± 34.29 vs. 206.41 ± 26.23 vs. 124.21 ± 14.73 vs. 108.46 ± 31.63 mm3; brain water content of the infarcted hemisphere was 82 ±± 0.25 vs. 81.5 ± 0.56 vs. 80.5 ± 0.22 vs. 80.5 ± 0.34%; and blood brain barrier permeability of the infarcted hemisphere was 11.31 ± 2.67 vs. 9.21 ± 2.28 vs. 5.83 ± 1.6 vs. 4.43 ± 0.93 µg/g tissue (p < 0.05 for measures in doses 0.5 and 0.75 mL/kg/day vs. controls. Oral administration of VOO reduces infarct volume, brain edema, blood brain barrier permeability, and improves neurologic deficit scores after transient MCAO in rats.

  9. Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

    Science.gov (United States)

    Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

    2017-12-01

    Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

  10. [Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

    Science.gov (United States)

    Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

    2012-11-01

    Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

  11. Computerized tomography of the brain and associated risk factors in 240 patients iwth reversible cerebral ischemic attacks (RIAs)

    International Nuclear Information System (INIS)

    Bozzao, L.; Fantozzi, L.M.; Carolei, A.; Pappata, S.; Vesentini, G.; Allori, L.; Rasura, M.; Fieschi, C.

    1985-01-01

    The frequency and distribution of focal low density cerebral ischemic lesions in RIA patients with regard to factors as age at onset, number and temporal profile of the reversible cerebral ischemic events on admission, presence of associated medical conditions such as hypertension and diabetes mellitus, have been investigated with computerized tomography of the brain. (author). 7 refs.; 1 tab

  12. The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Hansen, Bent Adel

    2008-01-01

    Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has...... been extensively studied and although the development of cerebral edema and ICH is of a complex and multifactorial nature, it is well established that ammonia plays a pivotal role. This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress...

  13. Pulmonary edema

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2014-04-01

    To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (pnecrosis at 21 days (pnecrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.

  15. Nutrition for brain recovery after ischemic stroke: an added value to rehabilitation.

    Science.gov (United States)

    Aquilani, Roberto; Sessarego, Paolo; Iadarola, Paolo; Barbieri, Annalisa; Boschi, Federica

    2011-06-01

    In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patient's life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

  16. High Altitude Cerebral Edema

    Science.gov (United States)

    1986-03-01

    described neuropathological findings of cerebral edema and wi4espread petechial hemorrhages in two HAPE fatalities and later reported (52...lethargy, thirst, indigestion, hysterical outburst o: other behavior disturbances, decreased concentration, fever , couhh and peripheral edema (52...autopsy results from the two fatalities in their series. In both cases multiple, widespread petechial hemorrhages were noted throughout the brain. One

  17. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  18. Objective Ventricle Segmentation in Brain CT with Ischemic Stroke Based on Anatomical Knowledge

    Directory of Open Access Journals (Sweden)

    Xiaohua Qian

    2017-01-01

    Full Text Available Ventricle segmentation is a challenging technique for the development of detection system of ischemic stroke in computed tomography (CT, as ischemic stroke regions are adjacent to the brain ventricle with similar intensity. To address this problem, we developed an objective segmentation system of brain ventricle in CT. The intensity distribution of the ventricle was estimated based on clustering technique, connectivity, and domain knowledge, and the initial ventricle segmentation results were then obtained. To exclude the stroke regions from initial segmentation, a combined segmentation strategy was proposed, which is composed of three different schemes: (1 the largest three-dimensional (3D connected component was considered as the ventricular region; (2 the big stroke areas were removed by the image difference methods based on searching optimal threshold values; (3 the small stroke regions were excluded by the adaptive template algorithm. The proposed method was evaluated on 50 cases of patients with ischemic stroke. The mean Dice, sensitivity, specificity, and root mean squared error were 0.9447, 0.969, 0.998, and 0.219 mm, respectively. This system can offer a desirable performance. Therefore, the proposed system is expected to bring insights into clinic research and the development of detection system of ischemic stroke in CT.

  19. Asymptomatic Brain Edema after Hemodialysis Initiation in a Patient with Severe Uremia

    Directory of Open Access Journals (Sweden)

    Kiichiro Fujisaki

    2017-01-01

    Full Text Available A 66-year-old man with severe renal insufficiency presented with mild confusion associated with uremia. Cranial magnetic resonance imaging (MRI showed no remarkable changes. The patient was placed on short-duration hemodialysis (2 hours with smaller surface area and low blood flow (100 mL/min to avoid dialysis disequilibrium syndrome (DDS. His consciousness gradually improved and he did not develop apparent DDS symptoms. However, T2-weighted FLAIR MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe on day 15. In other words, cranial MRI showed cerebral edema, indicating asymptomatic DDS. On day 29, cranial MRI showed a return to findings on admission. In this case, because the patient did not have apparent DDS symptoms despite MRI changes, we diagnosed asymptomatic cerebral edema. The patient was discharged on regular intermittent HD without any neurological deficits. No further neurological disturbances were noted during 1-year follow-up. MRI findings in ESKD patients without DDS symptoms help to clarify the diagnosis of cerebral edema. In this case, the patient did not have apparent DDS symptoms and was therefore diagnosed with asymptomatic cerebral edema.

  20. Non invasive brain stimulation to enhance post-stroke recovery

    OpenAIRE

    Nathalie Kubis; Nathalie Kubis

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical exci...

  1. The influence of general anesthesia on the brain in aged patients with previous ischemic cerebrovascular disease

    International Nuclear Information System (INIS)

    Kokubo, Yasuaki; Kayama, Takamasa; Kondo, Rei; Oki, Masato; Takaoka, Seiji

    2008-01-01

    Whenever we discuss the overall results of surgical treatment for unruptured cerebral aneurysms, especially in aged patients, we tend to consider advanced age or general anesthesia as causes for unfavorable results. There are no reports concerning ischemic stroke events following general anesthesia in aged patients with a prior history of cerebrovascular disease. The purpose of this study is to clarify the influence of general anesthesia on the brats in aged patients with a previous history of ischemic cerebrovascular disease. The subjects were 30 consecutive patients over 70 years of age with previous ischemic cerebrovascular disease who underwent various surgeries except brain and cardiac surgery under general anesthesia. The patients were 70 to 85 years old, with a mean age of 76. Twenty-three were men and 7 were women. Surgical procedures were 12 gastrointestinal, 6 orthopedic and 4 urogenital and others. The type of cerebrovascular disease evaluated by neuroradiologist and anesthesiologist based on MR imaging was devided as follows: 16 patients had minor stroke, 7 had transient ischemic attack/reversible ischemic neurological deficit (TIA/RIND) and 7 had asymptomatic cerebral infarction. MR angiography was also assessed to evaluate the main artery in the brain. Blood pressure and arterial blood gas (PaCO 2 ) during general anesthesia were analyzed, and the rate of systemic and neurological complications following general anesthesia were evaluated. MR angiography revealed no occlusion or severe stenosis of the main artery in the brain of any of the patients. The minimum systolic blood pressure showed less than 100 mmHg transiently for 5-20 minutes in 28 of 30 patients during general anesthesia. The minimum value was 65 mmHg maintained for 5 minutes. The minimum PaCO 2 during general anesthesia was as follows: 1 case 36 mmHg. There were no neurological complications following general anesthesia in this study. One of 30 patients (3.3%) had suffered from pneumonia

  2. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    Science.gov (United States)

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  3. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  4. RISK FACTORS AND ETIOLOGY OF TRANSIENT ISCHEMIC ATTACKS IN PATIENTS WITH BRAIN INFARCTION

    Directory of Open Access Journals (Sweden)

    Kavian Ghandehari

    2010-12-01

    Full Text Available   Abstract INTRODUCTION: Transient ischemic attacks (TIA are warnings of future stroke. There is no difference in risk factors, pathophysiology and prevention between TIA and brain infarction. methods: Consecutive patients with brain infarction admitted to Ghaem Hospital, Mashhad, Northeastern Iran, were enrolled in a prospective study during 2006. Diagnosis of ischemic stroke was established by a neurologist who also obtained history of TIA and vascular risk factors. All of the stroke patients underwent a standard battery of diagnostic investigations and etiology of ischemic stroke was determined by the Practical Iranian Criteria classification. Fisher’s exact test was used for statistical analysis. results: 348 stroke patients (186 women, 162 men were studied. History of TIA was present in 42 patients (29 women, 13 men, i.e. 12% of the stroke patients. TIA was more common in women (df=1, P=0.02. The frequency of hypertension, diabetes and ipsilateral carotid stenosis was not significantly different between patients with history of TIA and other stroke patients (P=0.87, P=0.64 and P=0.61, respectively. Hyper-cholesterolemia and smoking were significantly more frequent in stroke patients with history of TIA (P=0.011 and P=0.014, respectively. The frequency of TIA was not significantly different among patients with lacunar, versus large vessel territory infarcts (df=1, P=0.84. There was no significant difference in the frequency of various stroke etiologies in patients with and without history of TIA (df=4, P=0.61. CONCLUSIONS: Stroke patients with history of TIA have vascular risk factors similar to other stroke patients. A positive history of TIA does not affirm any specific etiology of ischemic stroke.     Keywords: Risk factors, etiology, transient ischemic attacks.

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

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...... in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p

  6. Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

    Science.gov (United States)

    Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

    2018-01-01

    Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

  7. Analysis of peritumoral edema

    International Nuclear Information System (INIS)

    Ikeda, Yukio; Nakazawa, Shozo

    1984-01-01

    In this study, seventy patients with brain tumors (34 glioblastomas, 21 meningiomas and 15 metastatic tumors) were examined by CT scan with and without contrast medium infusion and by postoperative histologic verification in all cases. Peritumoral hypodensity areas on CT scan have generally been interpreted as cerebral edema. Peritumoral edema as seen in CT scan was classified into four grades according to the ratio of the largest diameter of tumor and the size of the zone of edema. The grade of peritumoral edema was closely related to the degree of malignancy of the brain tumors. 8 out of 9 glioblastomas which demonstrated slight peritumorol edema, Grade I, had large cystic formations which seemed to serve as buffer action to compression mechanism by brain tumors. The grade of peritumoral edema was also related to the location of the tumor and venous involvement. Infusion of mannitol into the internal carotid artery is said to disrupt the blood-brain barrier. Intracarotid mannitol infusions in one glioblastoma produced the definite increase of contrast enhancement. Whether this phenomenon suggests an extravasation of contrast medium or the invasion of the tumor is not clear. The regional circulation and the extent of peritumoral edema was evaluated by means of dynamic CT scan. The CT number-time curve gave a few parameters. The peak value was considered to be related to the blood volume of the region of interest. It was a common finding that the peak value in the region of peritumoral edema was decreased, compared to the region of tumor and normal brain. Clinical application of dynamic CT scan may be useful to evaluate the regional circulation and the extent of peritumoral edema. (J.P.N.)

  8. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-11-01

    Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients' overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

  9. A Randomized Trial of the Effects of Nebulized Albuterol on Pulmonary Edema in Brain Dead Organ Donors

    Science.gov (United States)

    Ware, Lorraine B.; Landeck, Megan; Koyama, Tatsuki; Zhao, Zhiguo; Singer, Jonathan; Kern, Ryan; Neidlinger, Nikole; Nguyen, John; Johnson, Elizabeth; Janz, David R.; Bernard, Gordon R.; Lee, Jae W.; Matthay, Michael A.

    2013-01-01

    Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5 mg q4h) versus saline placebo during active donor management in 506 organ donors. The primary outcome was change in oxygenation (PaO2/FiO2) from enrollment to organ procurement. The albuterol (n=260) and placebo (n=246) groups were well matched for age, gender, ethnicity, smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p=0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%, p=0.44). Donors in the albuterol vs. placebo group were more likely to have the study drug dose reduced (13% vs. 1%, pdonor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia. High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema. PMID:24730050

  10. Pattern of brain injury and depressed heart rate variability in newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Metzler, Marina; Govindan, Rathinaswamy; Al-Shargabi, Tareq; Vezina, Gilbert; Andescavage, Nickie; Wang, Yunfei; du Plessis, Adre; Massaro, An N

    2017-09-01

    BackgroundDecreased heart rate variability (HRV) is a measure of autonomic dysfunction and brain injury in newborns with hypoxic ischemic encephalopathy (HIE). This study aimed to characterize the relationship between HRV and brain injury pattern using magnetic resonance imaging (MRI) in newborns with HIE undergoing therapeutic hypothermia.MethodsHRV metrics were quantified in the time domain (α S , α L , and root mean square at short (RMS S ) and long (RMS L ) timescales) and frequency domain (relative low-(LF) and high-frequency (HF) power) over 24-27 h of life. The brain injury pattern shown by MRI was classified as no injury, pure cortical/white matter injury, mixed watershed/mild basal ganglia injury, predominant basal ganglia or global injury, and death. HRV metrics were compared across brain injury pattern groups using a random-effects mixed model.ResultsData from 74 infants were analyzed. Brain injury pattern was significantly associated with the degree of HRV suppression. Specifically, negative associations were observed between the pattern of brain injury and RMS S (estimate -0.224, SE 0.082, P=0.006), RMS L (estimate -0.189, SE 0.082, P=0.021), and LF power (estimate -0.044, SE 0.016, P=0.006).ConclusionDegree of HRV depression is related to the pattern of brain injury. HRV monitoring may provide insights into the pattern of brain injury at the bedside.

  11. Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

    Science.gov (United States)

    Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

    2018-02-14

    Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

  12. ASPHYXIA, INTRACRANIAL HEMORRHAGES AND BRAIN EDEMA OF RISK CHILDREN IN THE ADVISORY INSTITUTE IN BITOLA FROM 1989-1994

    Directory of Open Access Journals (Sweden)

    M. ILIEVSKA,

    1997-09-01

    Full Text Available 3986 files have been examined in the Advisory Institute for a five year period in relation to the present risk factors in the pre, peri and postnatal period, the occurrence of asphyxia, I.H. (intracranial hemorrhages and brain edema and their outcome for the children. There were 958 or 32% risk children, out of them 206 or 22% were with asphyxia, 25 or 3% were with brain edema and 14 or 1,5% were with intracranial hemorrhages.The analysis for the risk factors shows that 119 of them were abortive , and from them 15% were born with asphyxia; 124 were SFD and 21% of them with asphyxia; 272 children weighed over 4500 gr., 7% of them with asphyxia and 0.4% with I.H., there were 68 twins, 12% of them with asphyxia. Out of the children with no risk registered, 6 were born with I.H., or 0,2%.Mothers under the age of 18 gave birth to 13% children with asphyxia; treated for sterility and anemia during pregnancy 15%; with increased blood pressure 14%; and 5% with maintained pregnancy.The highest delivery risk is present with children born with vacuum extraction (30% or every third child is with asphyxia and 3% with I.H. and with children delivered by caesarean section (14% with asphyxia.As for the position of the fetus-Citus pedalicus gave 55% children with asphyxia, and Situs pelvicus 12%.The worst damage is suffered by infants with premature amnion disruption (62% are with asphyxia; with the umbilical cord round the neck-56% with asphyxia and 6% with I.H.; and with muddled amniotic fluid and placenta pelvia-50%.The order of risk factors related to asphyxia, I.H. and brain edema is as follows: the first is premature amnion disruption, then follows the umbilical cord round the neck, the muddled amniotic fluid, and placenta previa and Citus pedalicus-which are obstetric problems. The next are the vacuum extraction and S.C. As for the gestatory period the order is as follows: first the abortive, then the twins and hypertrofic infants. The outcome of the

  13. Parameterized entropy analysis of EEG following hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Tong Shanbao; Bezerianos, Anastasios; Malhotra, Amit; Zhu Yisheng; Thakor, Nitish

    2003-01-01

    In the present study Tsallis and Renyi entropy methods were used to study the electric activity of brain following hypoxic-ischemic (HI) injury. We investigated the performances of these parameterized information measures in describing the electroencephalogram (EEG) signal of controlled experimental animal HI injury. The results show that (a): compared with Shannon and Renyi entropy, the parameterized Tsallis entropy acts like a spatial filter and the information rate can either tune to long range rhythms or to short abrupt changes, such as bursts or spikes during the beginning of recovery, by the entropic index q; (b): Renyi entropy is a compact and predictive indicator for monitoring the physiological changes during the recovery of brain injury. There is a reduction in the Renyi entropy after brain injury followed by a gradual recovery upon resuscitation

  14. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

    OpenAIRE

    Kubis, Nathalie

    2016-01-01

    Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excit...

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

    Science.gov (United States)

    Boss, H Myrthe; Van Schaik, Sander M; Witkamp, Theo D; Geerlings, Mirjam I; Weinstein, Henry C; Van den Berg-Vos, Renske M

    2017-10-01

    Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

  17. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE

    Directory of Open Access Journals (Sweden)

    Benjamin Harding

    2016-12-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI insult in neonatal rats via intracerebroventricular (ICV injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional

  18. Bone marrow edema of the knee joint

    International Nuclear Information System (INIS)

    Breitenseher, M.J.; Mayerhoefer, M.E.; Hofmann, S.

    2006-01-01

    Bone marrow edema of the knee joint is a frequent clinical picture in MR diagnostics. It can be accompanied by symptoms and pain in the joint. Diseases that are associated with bone marrow edema can be classified into different groups. Group 1 includes vascular ischemic bone marrow edema with osteonecrosis (synonyms: SONK or Ahlbaeck's disease), osteochondrosis dissecans, and bone marrow edema syndrome. Group 2 comprises traumatic or mechanical bone marrow edema. Group 3 encompasses reactive bone marrow edemas such as those occurring in gonarthrosis, postoperative bone marrow edemas, and reactive edemas in tumors or tumorlike diseases. Evidence for bone marrow edema is effectively provided by MRI, but purely morphological MR information is often unspecific so that anamnestic and clinical details are necessary in most cases for definitive disease classification. (orig.) [de

  19. NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

    Science.gov (United States)

    Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

    2017-11-14

    Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

  20. [Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

    Science.gov (United States)

    Huang, Hui-zhi; Wen, Xiao-hong; Liu, Hui; Huang, Jin-hua; Liu, Shang-quan; Ren, Wei-hua; Fang, Wen-xiang; Qian, Yin-feng; Hou, Wei-zhu; Yan, Ming-jie; Yao, You-heng; Li, Wei-Zu; Li, Qian-Jin

    2013-06-01

    To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. Human UCBMC intraperitoneal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development.

  1. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    Science.gov (United States)

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  2. Neural precursor cells in the ischemic brain - integration, cellular crosstalk and consequences for stroke recovery

    Directory of Open Access Journals (Sweden)

    Dirk M. Hermann

    2014-09-01

    Full Text Available After an ischemic stroke, neural precursor cells (NPCs proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate towards the ischemic lesion where they promote tissue remodelling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurological functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complementing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood-brain barrier integrity. On the contrary, local stem cell delivery, allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response.Herein we describe the diverse capabilities of exogenous (systemically vs locally transplanted NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors’ claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.

  3. Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Juan Liu

    2018-01-01

    Full Text Available Although extensive studies have identified large number of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

  4. An emboligenic pulmonary abscess leading to ischemic stroke and secondary brain abscess

    Directory of Open Access Journals (Sweden)

    Albrecht Philipp

    2012-11-01

    Full Text Available Abstract Background Ischemic stroke by septic embolism occurs primarily in the context of infective endocarditis or in patients with a right-to-left shunt and formation of a secondary cerebral abscess is a rare event. Erosion of pulmonary veins by a pulmonary abscess can lead to transcardiac septic embolism but to our knowledge no case of septic embolic ischemic stroke from a pulmonary abscess with secondary transformation into a brain abscess has been reported to date. Case presentation We report the case of a patient with a pulmonary abscess causing a septic embolic cerebral infarction which then transformed into a cerebral abscess. After antibiotic therapy and drainage of the abscess the patient could be rehabilitated and presented an impressive improvement of symptoms. Conclusion Septic embolism should be considered as cause of ischemic stroke in patients with pulmonary abscess and can be followed by formation of a secondary cerebral abscess. Early antibiotic treatment and repeated cranial CT-scans for detection of a secondary abscess should be performed.

  5. Potential roles of cell-derived microparticles in ischemic brain disease.

    Science.gov (United States)

    Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

    2009-10-01

    The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

  6. Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

    Science.gov (United States)

    Koppaka, S S; Puchowicz; LaManna, J C; Gatica, J E

    2008-01-01

    Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

  7. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    Science.gov (United States)

    2011-01-01

    Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

  8. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    Directory of Open Access Journals (Sweden)

    Suzuki Akifumi

    2011-03-01

    Full Text Available Abstract Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(- group (n = 83 and, who admitted between April 2004 and March 2005, into the edaravone(+ group (n = 93. Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI/iffusion-weighted magnetic resonance images (DWI] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset, early chronic (3-6 month, late chronic (7-12 months and old (≥13 months stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+ group compared with the edaravone(- group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute

  9. RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

    Science.gov (United States)

    Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

    2015-01-01

    Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

  10. Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

    Science.gov (United States)

    Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

    2015-08-01

    Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    Science.gov (United States)

    Massaro, An N; Govindan, R B; Vezina, Gilbert; Chang, Taeun; Andescavage, Nickie N; Wang, Yunfei; Al-Shargabi, Tareq; Metzler, Marina; Harris, Kari; du Plessis, Adre J

    2015-08-01

    Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury. Copyright © 2015 the American Physiological Society.

  12. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

    Directory of Open Access Journals (Sweden)

    Qing-quan Li

    2015-01-01

    Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  13. Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic-Ischemic Brain Injury.

    Science.gov (United States)

    Phan, Thanh G; Chen, Jian; Singhal, Shaloo; Ma, Henry; Clissold, Benjamin B; Ly, John; Beare, Richard

    2018-01-01

    Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. The inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003-2011). Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82-1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86-1.00). Our findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

  14. 采用CT技术研究颅脑损伤患者的早期神经功能恢复:脑水肿和脑肿胀的比较%CT study of patients neurological function recovery in the acute stage of brain injury:compared brain swelling and brain edema

    Institute of Scientific and Technical Information of China (English)

    李龙; 池晓宇; 黄新才; 刘卫国; 蒋德清

    2002-01-01

    @@ ckground: Secondary clinical manifestations following brain injury may be due to either intracranial hemorrhage or brain edema and brain swelling.But brain swelling hasn't been understand adequately in clinical practice.Objective: 71 patients with brain edema or brain swelling following brain injury admitted to our hospital during Jan 1998 to Dec 1999 were selected for this study.Their CT findings were compared,and CT characters of traumatic brain swelling and neurological function recovery were analyzed emphatically.Unit: Department of Radiology,Guangdong Provincial Corps Hospital,Chinese People's Armed Police Forces.

  15. The Effect of Antioxidant Melatonin on Mice Sensorimotor Gyri Following Induction of Brain Edema

    Directory of Open Access Journals (Sweden)

    Narges Jan-Zadeh

    2007-04-01

    Full Text Available Objective: Many factors can have a neuroprotective role after brain damage. The neuroprotective Effect of melatonin as a highly potent antioxidant and a free radical scavenger is well known. The purpose of this study was to investigate the effect of such melatonin on mice sensorimotorcortex after cold injury. Materials & Methods: In order to test such this objective, melatonin was injected intraperitoneally in 1,5,50 and 100 mg/kg to the mice (prepared by cortical cold injury induced brain lesion at the parietal lobe within three intervals (0.5 h before injury, 12 h and 48 h after injury. Brains were removed 72 hours after injury. Appropriate brain sections were stained with cresyl fast violet for histological assessment of cerebral cortex structures by using light microscope (LM. Results: After cell count of alive cells in the cerebral cortex the results showed that the cold injury caused significantly reduction in living cells. Melatonin administration in the experimental groups increased such living cells in compare to model group. Alive cells in cerebral cortex of animals which received melatonin at lower doses (1 and 5 mg/kg were lower than the control group, melatonin at optimum dose (50 mg/kg did not show any significant change in the number of alive cells in comparing with the control group (P>0/05. The highest dose (100mg/kg was toxic. Conclusion: Melatonin with optimum dose can reduce cerebral cortex damage due to cold injury in mouse model and overcome cell damages fallowing injury.

  16. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  17. The role of computed tomography in evaluation of a white matter edema during postoperative brain radiation therapy

    International Nuclear Information System (INIS)

    Thalacker, U.; Somogyi, A.; Nemeth, G.; Liszka, G.

    1998-01-01

    The aim of our study was to determine on CT whether a relation exists between a radiation induced brain edema, treated with diuretics and its corresponding Houndsfield Units (HU). Seventy-five patients (age 20 to 65 years), suffering from headaches but without hypertension, brain tumors or cerebral arteriosclerosis were examined as a reference group. The second group consisted of 20 patients with brain tumors, which underwent brain surgery. HU of the white matter were measured before radiation and after 10, 20, 30, 40 and 50 Gy. The third group consisted of 64 patients with brain tumors, that underwent postsurgical radiation therapy. Prior to radiation therapy 40 mg furosemide per os were given. CT-examinations, intensified diuretic therapy and follow-up examinations were performed as in group 2. If, despite therapy, the HU decreased, infusion of mannites was added. The second and third group of patients recieved radiation therapy with telecobalt and/or a linear accelerator (6 and 9 MeV X-ray). In the first group white matter density was >30 HU. In the second group white matter density was between 25 and 29 HU prior to diuretic therapy. Under 25 HU a continuous headache, vertigo and confusion ensued. Diuretic therapy was intensified until the measured values reached 25 to 29 HU. Forty-seven of 64 patients in the third group had 25 to 29 HU prior to radiation therapy. Despite prophylactic diuretic therapy in 28 cases density decreased to 20 to 24 HU. Improvement was achived with an additional glycerine per os. The measured values reached again 25 to 29 HU. In 1 case the values dropped under 20 HU. Additional mannite infusion was necessary. In 17 to 64 patients white matter density was >30 HU prior to radiation therapy, dropping to 25 to 29 HU during radiation. Prophylactic diuretic administration kept the values in this range. A correlation between age of the patient, radiation source, total dose, tumor histology and degree of change in HU was not found. (orig

  18. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.

    Science.gov (United States)

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-11-01

    Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability. Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

    Science.gov (United States)

    Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

    2015-07-01

    Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. © 2015 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-05-01

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  2. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  3. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-04-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

  4. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2016-01-01

    Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

  5. Noninvasive measures of brain edema predict outcome in pediatric cerebral malaria.

    Science.gov (United States)

    Kampondeni, Samuel D; Birbeck, Gretchen L; Seydel, Karl B; Beare, Nicholas A; Glover, Simon J; Hammond, Colleen A; Chilingulo, Cowles A; Taylor, Terrie E; Potchen, Michael J

    2018-01-01

    Increased brain volume (BV) and subsequent herniation are strongly associated with death in pediatric cerebral malaria (PCM), a leading killer of children in developing countries. Accurate noninvasive measures of BV are needed for optimal clinical trial design. Our objectives were to examine the performance of six different magnetic resonance imaging (MRI) BV quantification measures for predicting mortality in PCM and to review the advantages and disadvantages of each method. Receiver operator characteristics were generated from BV measures of MRIs of children admitted to an ongoing research project with PCM between 2009 and 2014. Fatal cases were matched to the next available survivor. A total of 78 MRIs of children aged 5 months to 13 years (mean 4.0 years), of which 45% were males, were included. Areas under the curve (AUC) with 95% confidence interval on measures from the initial MRIs were: Radiologist-derived score = 0.69 (0.58-0.79; P = 0.0037); prepontine cistern anteroposterior (AP) dimension = 0.70 (0.56-0.78; P = 0.0133); SamKam ratio [Rt. parietal lobe height/(prepontine AP dimension + fourth ventricle AP dimension)] = 0.74 (0.63-0.83; P = 0.0002); and global cerebrospinal fluid (CSF) space ascertained by ClearCanvas = 0.67 (0.55-0.77; P = 0.0137). For patients with serial MRIs ( n = 37), the day 2 global CSF space AUC was 0.87 (0.71-0.96; P dimension ≤3 mm; cisternal CSF volume ≤7.5 ml; SamKam ratio ≥6.5; and recovery factor ≤0.75. All noninvasive measures of BV performed well in predicting death and providing a proxy measure for brain volume. Initial MRI assessment may inform future clinical trials for subject selection, risk adjustment, or stratification. Measures of temporal change may be used to stage PCM.

  6. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

    Directory of Open Access Journals (Sweden)

    Hadar Arien-Zakay

    2010-09-01

    Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

  8. Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

    Science.gov (United States)

    Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

    2015-11-01

    Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure.

    Science.gov (United States)

    Lin, Hung; Chang, Ching-Ping; Lin, Hung-Jung; Lin, Mao-Tsun; Tsai, Cheng-Chia

    2012-05-01

    We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.

  10. Brain parenchyma PO2, PCO2, and pH during and after hypoxic, ischemic brain insult in dogs.

    Science.gov (United States)

    McKinley, B A; Morris, W P; Parmley, C L; Butler, B D

    1996-11-01

    1) The investigation of fiberoptic PO2, PCO2, and pH sensor technology as a monitor of brain parenchyma during and after brain injury, and 2) the comparison of brain parenchyma PO2, PCO2, and pH with intracranial pressure during and after hypoxic, ischemic brain insult. Prospective, controlled, animal study in an acute experimental preparation. Physiology laboratory in a university medical school. Fourteen mongrel dogs (20 to 35 kg), anesthetized, room-air ventilated. Anesthesia was induced with thiopental and maintained after intubation using 1% to 1.5% halothane in room air (FiO2 0.21). Mechanical ventilation was established to maintain end-tidal PCO2 approximately 35 torr (-4.7 kPa). Intravenous, femoral artery, and pulmonary artery catheters were placed. The common carotid arteries were surgically exposed, and ultrasonic blood flow probes were applied. A calibrated intracranial pressure probe was placed through a right-side transcranial bolt, and a calibrated intracranial chemistry probe with optical sensors for PO2, PCO2, and pH was placed through a left-side bolt into brain parenchyma. Brain insult was induced in the experimental group (n = 6) by hypoxia (FiO2 0.1), ischemia (bilateral carotid artery occlusion), and hypotension (mean arterial pressure [MAP] approximately 40 mm Hg produced with isoflurane approximately 4%). After 45 mins, carotid artery occlusion was released, FiO2 was reset to 0.21, and anesthetic was returned to halothane (approximately 1.25%). The control group (n = 5) had the same surgical preparation and sequence of anesthetic agent exposure but no brain insult. Monitored variables included brain parenchyma PO2, PCO2, and pH, which were monitored at 1-min intervals, and intracranial pressure, MAP, arterial hemoglobin oxygen saturation (by pulse oximetry), end-tidal PCO2, and carotid artery blood flow rate, for which data were collected at 15-min intervals for 7 hrs. Arterial and mixed venous blood gas analyses were done at approximately 1

  11. Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic–Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Thanh G. Phan

    2018-03-01

    Full Text Available BackgroundPrognostication following hypoxic ischemic encephalopathy (brain injury is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data.MethodThe inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003–2011. Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS, features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume associates of severe disability and death. We used the area under the ROC (auROC to determine accuracy of model. There were 41 (63.7% males patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82–1.00. At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86–1.00.ConclusionOur findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

  12. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

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    Artzi, Moran, E-mail: artzimy@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aizenstein, Orna, E-mail: ornaaize@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Jonas-Kimchi, Tali, E-mail: talijk@tlvmc.gov.il [Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Myers, Vicki, E-mail: vicki_myers@hotmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Hallevi, Hen, E-mail: hen.hallevi@gmail.com [Neurology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-09-15

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

  13. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

    International Nuclear Information System (INIS)

    Artzi, Moran; Aizenstein, Orna; Jonas-Kimchi, Tali; Myers, Vicki; Hallevi, Hen; Ben Bashat, Dafna

    2013-01-01

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice

  14. Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Antonio Chiaretti

    2013-06-01

    Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

  15. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    Science.gov (United States)

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

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

    Science.gov (United States)

    Feigin, I

    1981-03-01

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

  17. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

    Directory of Open Access Journals (Sweden)

    De-An Zhao

    Full Text Available Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

  20. What Is Macular Edema?

    Medline Plus

    Full Text Available ... the retina, where they are transmitted to the brain and interpreted as the images you see. It is the macula that is responsible for your pinpoint vision, allowing you to read, sew or recognize a face. Macular edema develops when blood vessels in the retina are leaking ...

  1. Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

    Science.gov (United States)

    Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

    2016-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

  2. Molecular pathophysiology of cerebral edema

    Science.gov (United States)

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

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

  3. USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

    Directory of Open Access Journals (Sweden)

    E. V. Shimchenko

    2014-01-01

    Full Text Available The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI for diagnostics of hypoxic-ischemic lesions in comparison with regular standard modes. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit. DW MRI has been offered as a method of prognosticating further neurological development of children on early stages. 

  4. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

    Science.gov (United States)

    Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

    2018-06-01

    Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Diffusion-weighted MR imaging in animal modil with acute ischemic brain infarction : evaluation of reversible brain injury

    International Nuclear Information System (INIS)

    Byun, Woo Mok; Chang, Han Won; Cho, Inn Ho; Hah, Jung Sang; Sung, Eon Gi

    2001-01-01

    To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by 99m TC-ECD brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared. SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p<0.01). After occlusion and reperfusion, the percentage of hemispheric lesions in Group I was less than in Group II. For the latter, the percentage of these lesions revealed by TTC staining and T2-weighted imaging was 48% and 59%, respectively, findings distinctly different from those for Group I. In addition, in group I, infarction was revealed by neither TTC staining nor T2-weighted imaging (p<0.01). The use of DWI to evaluate signal intensity ratios can help determine whether or not brain injury after temporary cerebral ischemia is reversible

  6. Application of diffusion-weighted echo planar imaging for diagnosis of small acute and subacute brain ischemic lesions

    International Nuclear Information System (INIS)

    Enomoto, Kyoko; Watanabe, Tsuneya; Amanuma, Makoto; Heshiki, Atsuko

    1997-01-01

    The aim of this study was to determine the utility of diffusion-weighted echo planar imaging (DW-EPI) for detecting acute and subacute brain ischemic foci less than 2 cm in size. Thirty patients underwent DW-EPI on a 1.5 T super-conducting unit using a SE-EPI sequence with an arbitrary pair of Stejskal-Tanner gradients applied along the imaging axes. DW-EPI demonstrated all the mast recent ischemic lesions as areas of decreased diffusion, providing greater conspicuity and larger size than conventional spin-echo imaging. DW-EPI is a promising method to detect within a subsecond early ischemia and reversible ischemic changes that are not demonstrate on routine spin-echo images. (author)

  7. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  8. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  9. Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

    Science.gov (United States)

    Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

  10. Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy.

    Science.gov (United States)

    Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Abreu, Maria T; Norenberg, Michael D

    2014-03-01

    Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy. We recently reported that conditioned media from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In this study, we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiate such effects. In addition, astrocytes exposed to conditioned media from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein up-regulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide, and that thioacetamide-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in acute hepatic encephalopathy, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. © 2013 International Society for Neurochemistry.

  11. Observation of the relationship between regional cerebral blood flow and brain functional changes in the patients with ischemic cerebrovascular diseases

    International Nuclear Information System (INIS)

    Guan Yihui; Lin Xiangtong; Liu Yongchang

    1994-01-01

    The brain perfusion SPECT imaging and functional changes in 27 patients with ischemic cerebrovascular diseases and 20 controls were investigated. Correlated with the clinical findings and MRI study, we discovered the lowered perfusion of Broca and Wernicke area is closely related with the aphasia caused by left basal ganglia infarction. In hemianopia group, as the visual function improved after the light stimulation treatment, the blood perfusion increased in occipital lobe. The lowered perfusion in vestibular center can be observed in vertigo group. From these studies, we concluded that 99m Tc-HMPAO brain SPECT imaging can partly reflect the brain functions

  12. Know your tools - concordance of different methods for measuring brain volume change after ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew [The University of Melbourne, Departments of Medicine and Neurology, Melbourne Brain Centre rate at The Royal Melbourne Hospital, Parkville, Victoria (Australia); Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M. [The University of Melbourne, Department of Radiology, The Royal Melbourne Hospital, Parkville (Australia); Churilov, Leonid [The University of Melbourne, The Florey Institute of Neurosciences and Mental Health, Parkville (Australia); Parsons, Mark W. [University of Newcastle and Hunter Medical Research Institute, Priority Research Centre for Translational Neuroscience and Mental Health, Newcastle (Australia)

    2015-07-15

    Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions. (orig.)

  13. Know your tools - concordance of different methods for measuring brain volume change after ischemic stroke

    International Nuclear Information System (INIS)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew; Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M.; Churilov, Leonid; Parsons, Mark W.

    2015-01-01

    Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions. (orig.)

  14. Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

    Directory of Open Access Journals (Sweden)

    Hori Motohide

    2012-11-01

    Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent and two-dimensional gel electrophoresis (2-DGE coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS, respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral. Previously known (such as the interleukin family and novel (Gabra6, Crtam genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2. The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions

  15. A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats

    Directory of Open Access Journals (Sweden)

    Fang Ming

    2010-12-01

    Full Text Available Abstract Background Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP at present. In this connection, 10% hypertonic saline (HS alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol. Results Adult male Sprague-Dawley (SD rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-3H(N]-mannitol. Brain water content (BWC as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na+ and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na+, plasma crystal osmotic pressure and difference value of concentration of serum Na+ and concentration of brain Na+ in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue. Conclusions We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.

  16. [Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain].

    Science.gov (United States)

    Castilla-Guerra, L; Fernández-Moreno, M C; Aguilera-Saborido, A; Solanella-Soler, J

    2016-01-01

    Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (±11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. H-LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  17. Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

    Directory of Open Access Journals (Sweden)

    Xiangpeng Yuan

    2014-11-01

    Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

  18. Hypothermia for the treatment of ischemic and hemorrhagic stroke.

    Science.gov (United States)

    Linares, Guillermo; Mayer, Stephan A

    2009-07-01

    Hypothermia is considered nature's "gold standard" for neuroprotection, and its efficacy for improving outcome in patients with hypoxic-ischemic brain injury as a result of cardiac arrest is well-established. Hypothermia reduces brain edema and intracranial pressure in patients with traumatic brain injury. By contrast, only a few small pilot studies have evaluated hypothermia as a treatment for acute ischemic stroke, and no controlled trials of hypothermia for hemorrhagic stroke have been performed. Logistic challenges present an important barrier to the widespread application of hypothermia for stroke, most importantly the need for high-quality critical care to start immediately in the emergency department. Rapid induction of hypothermia within 3 to 6 hrs of onset has been hampered by slow cooling rates, but is feasible. Delayed cooling for the treatment of cytotoxic brain edema does not provide definitive or lasting treatment for intracranial mass effect, and should not be used as an alternative to hemicraniectomy. Sustained fever control is feasible in patients with intracerebral and subarachnoid hemorrhage, but has yet to be tested in a phase III study. Important observations from studies investigating the use of hypothermia for stroke to date include the necessity for proactive antishivering therapy for successful cooling, the importance of slow controlled rewarming to avoid rebound brain edema, and the high risk for infectious and cardiovascular complications in this patient population. More research is clearly needed to bring us closer to the successful application of hypothermia in the treatment for stroke.

  19. Early predictors of brain damage in full-term newborns with hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Alkholy UM

    2017-08-01

    Full Text Available Usama M Alkholy,1 Nermin Abdalmonem,1 Ahmed Zaki,2 Yasser F Ali,1 Soma Abdalla Mohamed,3 Nasser I Abdelsalam,1 Mustafa Ismail Abu Hashim,1 Mohamed Abou Sekkien,3 Yasser Makram Elsherbiny4 1Pediatric Department, Zagazig University, Egypt; 2Pediatric Department, Mansoura University, Egypt; 3Pediatric Department, Al Azhar University, Egypt; 4Clinical Pathology Department, Menoufia University, Egypt Objective of the study: To evaluate the value of serum creatine phosphokinase-brain specific (CK-BB and urinary lactate/creatinine (L/C ratio as early indicators of brain damage in full-term newborns with hypoxic ischemic encephalopathy (HIE.Patients and methods: A case–control study including 25 full-term new-born infants with perinatal asphyxia who were admitted to neonatal intensive care unit (NICU with a proven diagnosis of HIE, compared to 20 healthy age- and sex-matched full-term newborns. All newborn infants were subjected to full history taking, clinical examination, routine investigations (cord blood gases and complete blood picture, and assessment of serum CK-BB (cord blood, 6 and 24 hours after birth and urinary L/C ratio (collected within the first 6 hours, on the 2nd and 3rd day after birth.Results: The serum CK-BB and urinary L/C ratio in infants with HIE were significantly higher in samples collected throughout the monitoring period when compared with the control group (all P<0.001. The cord CK-BB and urinary L/C ratio within the first 6 hours were significantly higher in infants with severe HIE than in infants with mild and moderate HIE (P<0.001. Cord CK-BB level at 12.5 U/L had 100% sensitivity and 84% specificity in the detection of severe HIE infants. Urinary L/C ratio of more than 10.5 collected within the first 6 hours after birth had 100% sensitivity and 78% specificity for the detection of severe HIE infants.Conclusion: The serum CK-BB and urinary L/C ratio in HIE infants were significantly increased early in the course of the

  20. Cerebral edema associated with acute hepatic failure.

    OpenAIRE

    Fujiwara, Masachika; Watanabe, Akiharu; Yamauchi, Yasuhiko; Hashimoto, Makoto; Nakatsukasa, Harushige; Kobayashi, Michio; Higashi, Toshihiro; Nagashima, Hideo

    1985-01-01

    The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64%) of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more fre...

  1. Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

    Science.gov (United States)

    Jiang, Xiao-Han; Wang, Si-Bo; Tian, Qian; Zhong, Chi; Zhang, Guan-Ling; Li, Ya-Jie; Lin, Pan; You, Yong; Guo, Rong; Cui, Ying-Hua; Xing, Ying-Qi

    2018-02-14

    Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. No. NCT02425696 ; registered on April 21, 2015.

  2. Modeling the ischemic blood-brain barrier; the effects of oxygen-glucose deprivation (OGD) on endothelial cells in culture

    DEFF Research Database (Denmark)

    Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

    Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... pathways across the barrier in ischemic and postischemic brain endothelium is important for developing new medical therapies capable to exploit the barrier changes occurring during/after ischemia to permeate in the brain and treat this devastating disease. Materials and Methods - Primary cultures...... the wall of brain capillaries. The restrictive nature of the BBB is due to the tight junctions (TJs), which seal the intercellular clefts, limiting the paracellular diffusion, efflux transporters, which extrude xenobiotics, and metabolizing enzymes, which may break down or convert molecules during...

  3. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  4. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

  5. Computerized detection of acute ischemic stroke in brain computed tomography images

    International Nuclear Information System (INIS)

    Nagashima, Hiroyuki; Shiraishi, Akihisa; Harakawa, Tetsumi; Shiraishi, Junji; Doi, Kunio; Sunaga, Shinichi

    2009-01-01

    The interpretation of acute ischemic stroke (AIS) in computed tomography (CT) images is a very difficult challenge for radiologists. To assist radiologists in CT image interpretation, we have developed a computerized method for the detection of AIS using 100 training cases and 60 testing cases. In our computerized method, the inclination of the isotropic brain CT volume data is corrected by rotation and shifting. The subtraction data for the contralateral volume is then derived by subtraction from the mirrored (right-left reversed) volume data. Initial candidates suspected to have experienced AIS were identified using multiple-thresholding and filtering techniques. Twenty-one image features of these candidates were extracted and applied to a rule-based test to identify final candidates for AIS. The detection sensitivity values for the training cases and for the testing cases were 95.0% with 3.1 false positives per case and 85.7% with 3.4 false positives per case, respectively. Our computerized method showed good performance in the detection of AIS by CT and is expected to be useful in decision-making by radiologists. (author)

  6. 3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, Fahmi; Marquering, Henk A.; Streekstra, Geert J.; Borst, Jordi; Beenen, Ludo F.M.; Majoie, Charles B.L.; Niesten, Joris M.; Velthuis, Birgitta K.; VanBavel, Ed

    2014-01-01

    Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition. Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from -2 (much worse) to 2 (much better). Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P = 0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS = -2, -1), 20 % remained unchanged (IS = 0), and 63 % improved (IS = +1, +2). The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement. (orig.)

  7. Hemostatic system changes predictive value in patients with ischemic brain disorders

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

  8. Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

    Science.gov (United States)

    Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

    2015-01-01

    Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

  9. Disruption of Intracellular ATP Generation and Tight Junction Protein Expression during the Course of Brain Edema Induced by Subacute Poisoning of 1,2-Dichloroethane

    Directory of Open Access Journals (Sweden)

    Gaoyang Wang

    2018-01-01

    Full Text Available The aim of this study was to explore changes in intracellular ATP generation and tight junction protein expression during the course of brain edema induced by subacute poisoning of 1,2-dichloroethane (1,2-DCE. Mice were exposed to 1.2 g/m3 1,2-DCE for 3.5 h per day for 1, 2, or 3 days, namely group A, B, and C. Na+-K+-ATPase and Ca2+-ATPase activity, ATP and lactic acid content, intracellular free Ca2+ concentration and ZO-1 and occludin expression in the brain were measured. Results of present study disclosed that Ca2+-ATPase activities in group B and C, and Na+/K+-ATPase activity in group C decreased, whereas intracellular free Ca2+ concentrations in group B and C increased significantly compared with control. Moreover, ATP content decreased, whereas lactic acid content increased significantly in group C compared with control. On the other hand, expressions of ZO-1 and occludin at both the protein and gene levels in group B and C decreased significantly compared with control. In conclusion, findings from this study suggest that calcium overload and depressed expression of tight junction associated proteins, such as ZO-1 and occludin might play an important role in the early phase of brain edema formation induced by subacute poisoning of 1,2-DCE.

  10. Dissociation of brain edema induced by cold injury in rat model. MR imaging and perfusion studies with 14C-iodo-antipyrine

    International Nuclear Information System (INIS)

    Itabashi, Yoko; Prado, G.L.M.; Abo, Mitsuru; Miura, Hiroyuki; Abe, Yoshinao

    2001-01-01

    The purpose of this study is to confirm whether T2-weighted imaging and perfusion imaging, i.e. autoradiogram of 14 C-iodoantipyrine, on the course of brain edema correspond to each other or not. Cold injured rat brains were used as a model and were sequentially examined by both methods and compared with each other and with histological specimens. Special focus relies on the time changes in the lesions. High SI of T2-weighted images were observed and the percentages in the high SI area to the total brain area in the same slice were 4.7±0.31, 5.6±0.46 and 3.4±0.42 for 6, 24 and 48 hours, respectively. By contrast, low perfusion areas were indicated in the perfusion study and their percentages were 4.6±0.55, 5.6±0.86 and 2.4±0.35 for 6, 24 and 48 hours, respectively. At 48 hours after cold injury, low perfusion areas were smaller than high SI areas. Moreover, high accumulation areas consisting of macrophages were observed surrounding necrosis. It is concluded that there is dissociation between perfusion and T2-weighted MR imaging, where the collection of macrophages surrounding edema lesions and necrosis had the same appearance on MRI and different accumulations on perfusion studies. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  12. What Is Macular Edema?

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Macular Edema Sections What Is Macular Edema? What Causes Macular ... Edema Diagnosis Macular Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué es un edema macular? ...

  13. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Español Eye Health / Eye Health A-Z Macular Edema Sections What Is Macular Edema? What Causes Macular ... Edema Diagnosis Macular Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué es un edema macular? ...

  14. Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators.

    Science.gov (United States)

    Hou, Huagang; Li, Hongbin; Dong, Ruhong; Khan, Nadeem; Swartz, Harold

    2014-06-01

    Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia, but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The Effects of Stereotactic Cerebroventricular Administration of Albumin, Mannitol, Hypertonic Sodium Chloride, Glycerin and Dextran in Rats with Experimental Brain Edema.

    Science.gov (United States)

    Ates, Tuncay; Gezercan, Yurdal; Menekse, Guner; Turkoz, Yusuf; Parlakpinar, Hakan; Okten, Ali Ihsan; Akyuva, Yener; Onal, Selami Cagatay

    2017-01-01

    To evaluate the effects of cerebroventricular administration of hyperoncotic/hyperosmotic agents on edematous brain tissue in rats with experimental head trauma. The study included 54 female Sprague-Dawley rats with weights ranging between 200 and 250 g. Six experimental groups were examined with each group containing 9 rats. All rats were exposed to head trauma, and treatment groups were administered 2 µl of one of the drugs (albumin, mannitol, hypertonic sodium chloride (NaCl), glycerin and dextran) 6, 12 and 24 hours after the trauma via the cerebroventricular route and using a stereotactic device. Rats were sacrificed 48 hours after the trauma, and brain tissues were extracted without damage. Biochemical analyses including reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were performed on the injured left hemisphere. Compared with the control group, the albumin, mannitol, 3% NaCl and glycerin treatment groups revealed dramatic increases in GSH levels (p < 0.001). Levels of MDA, which is the end-product of brain edema and lipid peroxidation, failed to show a statistically significant decrease, but there was a decreasing trend observed in the inter-group comparisons. NO levels were also decreased in the 3% NaCl treatment group. An analysis of TNF-α and IL-1β, two proinflammatory cytokines associated with the trauma, revealed that IL-1β decreased significantly in all treatment groups (p=0.001), whereas no significant difference was detected in TNF-α levels. Cerebroventricular administration of hyperoncotic/hyperosmotic agents provides substantial effects on the treatment of brain edema.

  16. The effects of citicoline on acute ischemic stroke

    DEFF Research Database (Denmark)

    Overgaard, Karsten

    2014-01-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression...... lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute...... therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11...

  17. Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

    International Nuclear Information System (INIS)

    Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

    2005-01-01

    We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

  18. The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

    Directory of Open Access Journals (Sweden)

    Heng-Chih Chang

    Full Text Available Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and

  19. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    Totarol activates PI3K/Akt pathway in neurons. • Totarol induces HO-1, GSH and SOD expression in vitro and in vivo. • Totarol exhibits neuroprotective effects in rat brain ischemic stroke model.

  20. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    Totarol activates PI3K/Akt pathway in neurons. • Totarol induces HO-1, GSH and SOD expression in vitro and in vivo. • Totarol exhibits neuroprotective effects in rat brain ischemic stroke model.

  1. MRI patterns of hypoxic-ischemic brain injury in preterm and full term infants – classical and less common MR findings

    International Nuclear Information System (INIS)

    Cabaj, Astra; Bekiesińska-Figatowska, Monika; Mądzik, Jaroslaw

    2012-01-01

    Hypoxic-ischemic brain injury occurring in antenatal, perinatal or early postnatal period constitutes an important diagnostic problem in both term and prematurely born neonates. Over the past several years magnetic resonance imaging (MRI) has become relatively easily accessible in Poland. On the basis of the central nervous system MRI, the experienced radiologist are able to determine the location of the hypoxic-ischemic lesions, their extent and evolution. Therefore he can help clinicians to answer the question whether the brain damage of the newborn is responsible for its clinical condition and he can contribute to determining the prognosis of the infant’s future development. The aim of this study is to present the current knowledge of different types of hypoxic-ischemic brain lesions based on our personal experience and MR images from the archives of the Department of Diagnostic Imaging at the Institute of Mother and Child

  2. Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

    Science.gov (United States)

    Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

    2011-05-01

    Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

  3. NeuroSPECT assessment of ischemic penumbra in acute brain infarct: control of intra-arterial thrombolysis

    International Nuclear Information System (INIS)

    Mena, F.J.; Mena, I.; Contreras, I.; Soto, F.; Ducci, H.; Fruns, M.

    2002-01-01

    Introduction: Brain infarct is the most common cause of incapacity in adults, the second cause of dementia and the 2nd or 3rd cause of death. Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis in the first hours of evolution. Thrombolysis is now an approved and efficacious method of treatment for acute ischemic stroke. During the first 3 hours of evolution, intravenous administration of plasminogen activator (tPA) can be performed. The window of time of treatment is expanded to 6 hours with the intra-arterial super selective route for thrombolysis. Aim: The aim of this study was to define levels of reversible ischemia (penumbra) demonstrated by statistically evaluated HMPAO Tc99m NeuroSPECT performed before and after intra-arterial thrombolysis in the treatment of acute infarct. Materials and Methods: 21 patients were treated during the first 6 hours of evolution of an acute ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan to rule hemorrhage or established infarct. 3) I.V injection of 1100MBq Tc99m HMPAO (Ceretec tm) 4) Conventional cerebral angiography and intra-arterial thrombolysis and/or angioplasty/stenting if necessary. 5) NeuroSPECT assessment of ischemic penumbra. 6) Control at 24 hrs with NeuroSPECT. NeuroSPECT image acquisition is performed immediately following arterial thrombolysis with a dual Head Camera, SHR collimators and conventional protocol. Image processing was performed using the Segami Software, as previously reported in Alasbimn Journal2 (7): April 2000. http://www.alasbimnjournal.cl. The analysis consists of 1) Tallairach brain volume normalization. 2) Voxel by voxel comparison of the individual brain cortex uptake normalized to the maximum in the cortex with a normal database of 24 age-matched controls. Results: The results are expressed in standard deviations (S.D.) below the normal mean. Normal mean is 72% + 6. Only voxels between

  4. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van; Ceulemans, Berten; Laridon, Annick; Jorens, Philippe G.

    2003-01-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  5. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van [Department of Radiology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Ceulemans, Berten; Laridon, Annick [Department of Pediatric Neurology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Jorens, Philippe G. [Department of Pediatric Intensive Care Medicine, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2003-12-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  6. Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells.

    Science.gov (United States)

    Koh, Phil-Ok

    2017-09-01

    α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

  7. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

    Directory of Open Access Journals (Sweden)

    Hong-Jhang Chen

    Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

  8. Netrin-1 Ameliorates Blood-Brain Barrier Impairment Secondary to Ischemic Stroke via the Activation of PI3K Pathway

    Directory of Open Access Journals (Sweden)

    Jian Yu

    2017-12-01

    Full Text Available Secondary impairment of blood-brain barrier (BBB occurs in the remote thalamus after ischemic stroke. Netrin-1, an axonal guidance molecule, presents bifunctional effects on blood vessels through receptor-dependent pathways. This study investigates whether netrin-1 protects BBB against secondary injury. Netrin-1 (600 ng/d for 7 days was intracerebroventricularly infused 24 h after middle cerebral artery occlusion (MCAO in hypertensive rats. Neurological function was assessed 8 and 14 days after MCAO, and the permeability of BBB in the ipsilateral thalamus was detected. The viability of brain microvascular endothelial cells was determined after being disposed with netrin-1 (50 ng/mL before oxygen-glucose deprivation (OGD. The role of netrin-1 was further explored by examining its receptors and their function. We found that netrin-1 infusion improved neurological function, attenuated secondary impairment of BBB by up-regulating the levels of tight junction proteins and diminishing extravasation of albumin, with autophagy activation 14 days after MCAO. Netrin-1 also enhanced cell survival and autophagy activity in OGD-treated cells, inhibited by UNC5H2 siRNA transfection. Furthermore, the beneficial effects of netrin-1 were suppressed by PI3K inhibitors 3-Methyladenine and LY294002. Our results showed that netrin-1 ameliorated BBB impairment secondary to ischemic stroke by promoting tight junction function and endothelial survival. PI3K-mediated autophagy activation depending on UNC5H2 receptor could be an underlying mechanism.

  9. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    International Nuclear Information System (INIS)

    Schmitz, Stephan A.; O'Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V.; Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P.

    2007-01-01

    Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

  10. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

    2007-11-15

    Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

  11. What Is Macular Edema?

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    Full Text Available ... Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ... Macular Edema Sections What Is Macular Edema? What Causes Macular Edema? Macular ...

  12. Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

    Directory of Open Access Journals (Sweden)

    Gratianne Rabiller

    2015-10-01

    Full Text Available Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV, θ (4–8 Hz, 10 μV, α (8–12 Hz, 20–200 μV, β (12–30 Hz, 5–10 μV, and γ (30–80 Hz, low amplitude. Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy.

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

    Science.gov (United States)

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

    2014-03-01

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

  14. Neural stem cells in the ischemic and injured brain: endogenous and transplanted.

    Science.gov (United States)

    Dong, Jing; Liu, Baohua; Song, Lei; Lu, Lei; Xu, Haitao; Gu, Yue

    2012-12-01

    Neural stem cells functions as the pool of new neurons in adult brain, and plays important roles in normal brain function. Additionally, this pool reacts to brain ischemia, hemorrhage, trauma and many kinds of diseases, serving as endogenous repair mechanisms. The present manuscript discussed the responses of adult neurogenesis to brain ischemia and other insults, then the potential of neural stem cell transplantation therapy to treat such brain injury conditions.

  15. Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

    Science.gov (United States)

    Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

    2017-01-01

    Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  16. Probucol plus cilostazol attenuate hypercholesterolemia‑induced exacerbation in ischemic brain injury via anti-inflammatory effects.

    Science.gov (United States)

    Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-09-01

    Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.

  17. Serial measurements of N-terminal pro-brain natriuretic peptide after acute ischemic stroke

    DEFF Research Database (Denmark)

    Jensen, J.K.; Mickley, H.; Bak, S.

    2006-01-01

    consecutive patients with acute ischemic stroke. RESULTS: NT-proBNP peaked the day after onset of symptoms (p = 0.007) followed by a decrease until day 5 (p = 0.001, ANOVA). At 6-month follow-up the difference in the level of NT-proBNP was unchanged compared to day 5 (p = 0.42). NT-proBNP levels > or =615 pg...

  18. Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

    Science.gov (United States)

    Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

    2006-06-21

    Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

  19. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    Directory of Open Access Journals (Sweden)

    Yong-Hong Yi

    2008-06-01

    Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

  20. Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

    Science.gov (United States)

    Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

    2018-04-23

    Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Macular Edema ... Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué es un edema macular? Dec. 01, 2010 ...

  2. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Eye Health A-Z Symptoms Glasses & Contacts Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye ... Macular Edema Symptoms Macular Edema Diagnosis Macular Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué ...

  3. What Is Macular Edema?

    Medline Plus

    Full Text Available ... Macular Edema Treatment What Is Macular Edema? Leer en Español: ¿Qué es un edema macular? Dec. 01, 2010 Macular edema is swelling or thickening of the eye's macula, the part of your eye responsible for detailed, central vision. The macula is a very small area ...

  4. Effects of JPEG data compression on magnetic resonance imaging evaluation of small vessels ischemic lesions of the brain

    International Nuclear Information System (INIS)

    Kuriki, Paulo Eduardo de Aguiar; Abdala, Nitamar; Nogueira, Roberto Gomes; Carrete Junior, Henrique; Szejnfeld, Jacob

    2006-01-01

    Objective: to establish the maximum achievable JPEG compression ratio without affecting quantitative and qualitative magnetic resonance imaging analysis of ischemic lesion in small vessels of the brain. Material and method: fifteen DICOM images were converted to JPEG with a compression ratio of 1:10 to 1:60 and were assessed together with the original images by three neuro radiologists. The number, morphology and signal intensity of the lesions were analyzed. Results: lesions were properly identified up to a 1:30 ratio. More lesions were identified with a 1:10 ratio then in the original images. Morphology and edges were properly evaluated up toa 1:40 ratio. Compression did not affect signal. Conclusion: small lesions were identified ( < 2 mm ) and in all compression ratios the JPEG algorithm generated image noise that misled observers to identify more lesions in JPEG images then in DICOM images, thus generating false-positive results.(author)

  5. Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, F.; Beenen, L.F.M.; Streekstra, G.J.; Janssen, N.Y.; Jong, H.W. de; Riordan, A.; Roos, Y.B.; Majoie, C.B.; Bavel, E. van; Marquering, H.A.

    2013-01-01

    Objective: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. Results: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement

  6. Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Fahmi, F., E-mail: f.fahmi@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Beenen, L.F.M., E-mail: l.f.beenen@amc.uva.nl [Department of Radiology, AMC, Amsterdam (Netherlands); Streekstra, G.J., E-mail: g.j.streekstra@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Janssen, N.Y., E-mail: n.n.janssen@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Jong, H.W. de, E-mail: H.W.A.M.deJong@umcutrecht.nl [Department of Radiology, UMC Utrecht, 3584CX, Utrecht (Netherlands); Riordan, A., E-mail: alan.riordan@gmail.com [Department of Radiology, UMC Utrecht, 3584CX, Utrecht (Netherlands); Roos, Y.B., E-mail: y.b.roos@amc.uva.nl [Department of Neurology, AMC, Amsterdam (Netherlands); Majoie, C.B., E-mail: c.b.majoie@amc.uva.nl [Department of Radiology, AMC, Amsterdam (Netherlands); Bavel, E. van, E-mail: e.vanbavel@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Marquering, H.A., E-mail: h.a.marquering@amc.uva.nl [Department of Biomedical Engineering and Physics, AMC, Amsterdam (Netherlands); Department of Radiology, AMC, Amsterdam (Netherlands)

    2013-12-01

    Objective: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. Results: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement.

  7. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

    Science.gov (United States)

    Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

    2016-02-15

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

  8. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy.

    Science.gov (United States)

    Cavalieri, Margherita; Schmidt, Reinhold; Chen, Christopher; Mok, Vincent; de Freitas, Gabriel R; Song, Swithin; Yi, Qilong; Ropele, Stefan; Grazer, Anja; Homayoon, Nina; Enzinger, Christian; Loh, Katherine; Wong, Ka Sing Lawrence; Wong, Adrian; Xiong, Yunyun; Chang, Hui Meng; Wong, Meng Cheong; Fazekas, Franz; Eikelboom, John W; Hankey, Graeme J

    2012-12-01

    Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions. A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities. After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039). Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.

  9. Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

    International Nuclear Information System (INIS)

    Wintermark, Pia; Labrecque, Michelle; Hansen, Anne; Warfield, Simon K.; DeHart, Stephanie

    2010-01-01

    Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

  10. Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

    Energy Technology Data Exchange (ETDEWEB)

    Wintermark, Pia [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Children' s Hospital Boston, Department of Radiology, Boston, MA (United States); Montreal Children' s Hospital, Division of Newborn Medicine, Montreal, QC (Canada); Labrecque, Michelle; Hansen, Anne [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Warfield, Simon K.; DeHart, Stephanie [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)

    2010-12-15

    Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

  11. PET/CT imaging of striatal dopamine transporters in a newborn piglet model of hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoming; Wang Xiaoyu; Cao Li; Guo Qiyong

    2013-01-01

    Objective: To investigate changes of striatal DAT following hypoxic ischemic (HI) brain injury in newborn piglets using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT, and to evaluate the value of 11 C-CFT PET/CT in brain injury. Methods: Newborn piglets with HI brain injury (n=20) were taken as a model group,and five piglets were used as a control group. Radioligand 11 C-CFT (55.5-74.0 MBq) was injected through the jugular vein, and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets. The ST/occipital lobe (OC) ratio was calculated. Model group was divided into 0-6 h, 20-24 h, 44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time. The piglets were sacrificed immediately after 11 C-CFT PET/CT scanning, and then the brains were removed for pathological analysis. Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis. Results: After intravenous injection of 11 C-CFT, the radioactivity accumulation in cortical, striatum, and cerebellum was shown clearly in the control and model groups. The radioactivity accumulation was lower in the white matter. The radioactivity in cortical and cerebellum exhibited decreased with time, while the striatum was still clear. After HI, the ST/OC activity ratio in the striatum was initially increased, and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of the control group (1.18 ± 0.06; F=4.658, P<0.05), followed by a gradual decrease. ST/OC ratios of other HI subgroups were 1.27 ±0.01, 1.27 ±0.10 and 1.18 ±0.05, respectively. There was a positive correlation between the number of DAT positive neurons ((13 ± 3), (13 ± 4), (8 ±3) and (4 ±4)/high power field) and 11 C-CFT ST/OC activity ratios (r=0.844, P<0.05). Conclusion: 11 C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum, and the amount of DAT is related to the severity of the ischemic insult

  12. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway.

    Directory of Open Access Journals (Sweden)

    Jingxian Wu

    Full Text Available Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(PH: quinone oxidoreductase1 (NQO1 induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2 to antioxidant response element (ARE were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage.

  13. Neuroprotection by Curcumin in Ischemic Brain Injury Involves the Akt/Nrf2 Pathway

    Science.gov (United States)

    Wu, Jingxian; Li, Qiong; Wang, Xiaoyan; Yu, Shanshan; Li, Lan; Wu, Xuemei; Chen, Yanlin; Zhao, Jing; Zhao, Yong

    2013-01-01

    Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE) were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage. PMID:23555802

  14. Transient ischemic attacks and presence of an acute brain lesion in diffusion-weighted MRI: study of 50 patients

    Directory of Open Access Journals (Sweden)

    Sabeti M

    2012-10-01

    Full Text Available Background: Finding an acute brain lesion by diffusion-weighted (DW MRI upon an episode of transient ischemic attack (TIA is a predictor of imminent stroke in the near future. Therefore, exploring risk factors associated with lesions in DW-MRI of the brain is important in adopting an approach to TIA management. In the current study, we tried to determine the risk factors associated with lesions in DW-MRI of the brain in patients experiencing TIA episodes.Methods: Fifty patients with TIA were recruited consecutively in Sina Hospital, Tehran, Iran, over a 6-month period between July 2008 and January 2009. All of the patients underwent a complete neurological examination and laboratory tests. Brain DW-MRIs were performed for all the patients within 72 hours of a TIA episode.Results: DW-MRI revealed an acute lesion in 16% of the participants. There was a significant correlation between presence of an acute lesion in DW-MRI and TIA duration, history of diabetes mellitus and presence of unilateral facial palsy (P=0.0003, P=0.02 and P=0.008, respectively. Other variables such as age, hypertension, hyperlipidemia, past history of TIA, headache, vertigo, and sensory or visual disturbances had no significant relation with the presence of an acute lesion in DW-MRI.Conclusion: Duration of TIA, presence of diabetes mellitus and unilateral facial palsy are risk factors for an acute lesion in DW-MRI, meaning that patients with such risk factors are at risk for stroke in the near future.

  15. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Science.gov (United States)

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  16. Dynamics of cerebral edema and the apparent diffusion coefficient of water changes in patients with severe traumatic brain injury. A prospective MRI study

    International Nuclear Information System (INIS)

    Pasco, Anne; Minassian, Aram Ter; Chapon, Catherine; Lemaire, Laurent; Benoit, Jean-Pierre; Jeune, Jean-Jacques Le; Franconi, Florence; Darabi, Dana; Caron, Christine

    2006-01-01

    The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3±0.7 is significantly reduced compared to normal-appearing parenchyma (0.51±0.12 * 10 -3 mm 2 /s vs. 0.76±0.03 * 10 -3 mm 2 /s, n=12, P MRI2 =0.40±0.11 * 10 -3 mm 2 /s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69±0.05 * 10 -3 mm 2 /s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34±0.22 * 10 -3 mm 2 /s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI. (orig.)

  17. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

    Science.gov (United States)

    Park-Hansen, Jesper; Holme, Susanne J V; Irmukhamedov, Akhmadjon; Carranza, Christian L; Greve, Anders M; Al-Farra, Gina; Riis, Robert G C; Nilsson, Brian; Clausen, Johan S R; Nørskov, Anne S; Kruuse, Christina R; Rostrup, Egill; Dominguez, Helena

    2018-05-23

    Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

  18. Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Orrock, Janet E; Panchapakesan, Karuna; Vezina, Gilbert; Chang, Taeun; Harris, Kari; Wang, Yunfei; Knoblach, Susan; Massaro, An N

    2016-05-01

    Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

  19. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Sung-Rae Cho

    2016-09-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

  20. Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

    Science.gov (United States)

    Hennebelle, Marie; Zhang, Zhichao; Metherel, Adam H; Kitson, Alex P; Otoki, Yurika; Richardson, Christine E; Yang, Jun; Lee, Kin Sing Stephen; Hammock, Bruce D; Zhang, Liang; Bazinet, Richard P; Taha, Ameer Y

    2017-06-28

    Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO 2 -induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

  1. Long-Term Functional and Psychosocial Outcomes After Hypoxic-Ischemic Brain Injury: A Case-Controlled Comparison to Traumatic Brain Injury.

    Science.gov (United States)

    Harbinson, Meredith; Zarshenas, Sareh; Cullen, Nora K

    2017-12-01

    Despite the increasing rate of survival from hypoxic-ischemic brain injury (HIBI), there is a paucity of evidence on the long-term functional outcomes after inpatient rehabilitation among these nontrauma patients compared to patients with traumatic brain injury (TBI). To compare functional and psychosocial outcomes of patients with HIBI to those of case-matched patients with TBI 4-11 years after brain insult. Retrospective, matched case-controlled study. Data at the time of rehabilitation admission and discharge were collected as part of a larger acquired brain injury (ABI) database at Toronto Rehabilitation Institute (TRI) between 1999 and 2009. This study consisted of 11 patients with HIBI and 11 patients with TBI that attended the neuro-rehabilitation day program at TRI during a similar time frame and were matched on age, admission Functional Independence Measure (FIM) scores, and acute care length of stay (ALOS). At 4-11 years following brain insult, patients were reassessed using the FIM, Disability Rating Scale (DRS), Personal Health Questionnaire Depression Scale (PHQ-9), and the Mayo-Portland Adaptability Inventory 4 (MPAI-4). At follow-up, patients with HIBI had significantly lower FIM motor and cognitive scores than patients with TBI (75.3 ± 20.6 versus 88.1 ± 4.78, P MPAI-4 at follow-up (P < .05). The study results suggest that patients with HIBI achieve less long-term functional improvements compared to patients with TBI. Further research is warranted to compare the components of inpatient rehabilitation while adjusting for demographics and clinical characteristics between these 2 groups of patients. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  2. Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis.

    Science.gov (United States)

    Beez, Thomas; Steiger, Hans-Jakob; Etminan, Nima

    2017-12-07

    The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms

  3. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

    Science.gov (United States)

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

    2014-01-29

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

  4. Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

    Science.gov (United States)

    Schrader, I; Wilk, D; Jansen, O; Riedel, C

    2013-09-01

    To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. © Georg Thieme Verlag

  5. Glucocorticoids and Preterm Hypoxic-Ischemic Brain Injury: The Good and the Bad

    Directory of Open Access Journals (Sweden)

    Laura Bennet

    2012-01-01

    Full Text Available Fetuses at risk of premature delivery are now routinely exposed to maternal treatment with synthetic glucocorticoids. In randomized clinical trials, these substantially reduce acute neonatal systemic morbidity, and mortality, after premature birth and reduce intraventricular hemorrhage. However, the overall neurodevelopmental impact is surprisingly unclear; worryingly, postnatal glucocorticoids are consistently associated with impaired brain development. We review the clinical and experimental evidence on how glucocorticoids may affect the developing brain and highlight the need for systematic research.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

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

  8. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    Science.gov (United States)

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  9. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  10. What Is Macular Edema?

    Medline Plus

    Full Text Available ... remains. Macular edema is often a complication of diabetic retinopathy , and is the most common form of ... 2016 Study Compares Eylea, Lucentis and Avastin for Diabetic Macular Edema Jul 17, 2015 Top 5 Risk ...

  11. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... brains NAPE accumulation could not be detected (detection limit 0.09 %)]; and 2) this age pattern of accumulation can be explained by a combination of the decreased activity of N- acyltransferase and the increased activity of NAPE-PLD during development. These results point out that it would...

  12. Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging.

    Science.gov (United States)

    Bivard, Andrew; Parsons, Mark

    2018-02-01

    The clinical practice of acute ischemic stroke treatment has undergone a major change over the last 5 years, as multimodal imaging becomes more accessible, and evidence mounts that individualized treatment is possible. Multimodal imaging performed before treatment provides invaluable information to treating clinicians, which includes confirmation of the diagnosis, and provides guidance on the appropriateness and the likely outcome of intravenous or endovascular treatment for individual patients (and their families). However, often health systems struggle to keep pace with science; thus, a one-size fits all protocol-driven basic imaging approach is still the norm in many stroke centers. Comprehensive multimodal computed tomography (CT) (incorporating noncontrast CT, CT angiography, and perfusion CT) provides rapid, reliable information about stroke pathophysiology that cannot be provided by more limited imaging prior to treatment. Multimodal CT identifies treatment responders for both intravenous thrombolysis and endovascular therapy. Now we are in the era of thrombectomy, the use of multimodal imaging routinely to guide treatment can no longer be avoided. In light of the ground breaking thrombectomy trial results and previous studies validating the use of multimodal imaging, there is now a strong rationale for performing comprehensive multimodal CT assessments before treatment as a standard of care for all stroke patients.

  13. The effect of whole-body cooling on brain metabolism following perinatal hypoxic-ischemic injury.

    Science.gov (United States)

    Corbo, Elizabeth T; Bartnik-Olson, Brenda L; Machado, Sandra; Merritt, T Allen; Peverini, Ricardo; Wycliffe, Nathaniel; Ashwal, Stephen

    2012-01-01

    Magnetic resonance imaging (MRI) and spectroscopy (MRS) have proven valuable in evaluating neonatal hypoxic-ischemic injury (HII). MRI scores in the basal ganglia of HII/HT(+) neonates were significantly lower than HII/HT(-) neonates, indicating less severe injury and were associated with lower discharge encephalopathy severity scores in the HII/HT(+) group (P = 0.01). Lactate (Lac) was detected in the occipital gray matter (OGM) and thalamus (TH) of significantly more HII/HT(-) neonates (31.6 and 35.3%) as compared to the HII/HT(+) group (10.5 and 15.8%). In contrast, the -N-acetylaspartate (NAA)-based ratios in the OGM and TH did not differ between the HII groups. Our data show that the HT was associated with a decrease in the number of HII neonates with detectable cortical and subcortical Lac as well as a decrease in the number of MRI-detectable subcortical lesions. We retrospectively compared the medical and neuroimaging data of 19 HII neonates who received 72 h of whole-body cooling (HII/HT(+)) with those of 19 noncooled HII neonates (HII/HT(-)) to determine whether hypothermia was associated with improved recovery from the injury as measured by MRI and MRS within the first 14 days of life. MRI scores and metabolite ratios of HII/HT(+) and HII/HT(-) neonates were also compared with nine healthy, nonasphyxiated "control" neonates.

  14. Ischemic tolerance in pre-myelinated white matter: the role of astrocyte glycogen in brain pathology.

    Science.gov (United States)

    Fern, Robert

    2015-06-01

    In isolated white matter, ischemic tolerance changes dramatically in the period immediately before the onset of myelination. In the absence of an extrinsic energy source, postnatal day 0 to 2 (P0 to P2) white matter axons are here shown to maintain excitability for over twice as long as axons >P2, a differential that was dependent on glycogen metabolism. Prolonged withdrawal of extrinsic energy supply tended to spare axons in zones around astrocytes, which are shown to be the sole repository for glycogen particles in developing white matter. Analysis of mitochondrial volume fraction revealed that neither axons nor astrocytes had a low metabolic rate in neonatal white matter, while oligodendroglia at older ages had an elevated metabolism. The astrocyte population is established early in neural development, and exhibits reduced cell density as maturation progresses and white matter expands. The findings show that this event establishes the necessary conditions for ischemia sensitivity in white matter and indicates that astrocyte proximity may be significant for the survival of neuronal elements in conditions associated with compromised energy supply.

  15. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

    OpenAIRE

    Lou Yongli; Guo Dewei; Zhang Hui; Song Laijun

    2016-01-01

    In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs) cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI) brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were adminis...

  16. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

    OpenAIRE

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-01-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revea...

  17. Edema associated with quetiapine

    Science.gov (United States)

    Koleva, Hristina K.; Erickson, Mark A.; Vanderlip, Erik R.; Tansey, Janeta; Mac, Joseph; Fiedorowicz, Jess G.

    2010-01-01

    Background Edema associated with quetiapine has been described in only one case report to date and represents a potentially serious adverse reaction. Methods We present a case series of three patients who developed bilateral leg edema following initiation of quetiapine. Results One of these patients had a recurrence of edema with subsequent rechallenge. Another patient developed quetiapine-induced edema following a prior episode of olanzapine-induced edema. All the cases present a compelling temporal relationship between the drug challenge and the adverse event. Conclusions Prompt recognition and intervention with discontinuation of the offending agent is important for this potentially serious, seemingly idiosyncratic, vascular complication. PMID:19439156

  18. Analysis of peritumoral cerebral edema of meningiomas

    International Nuclear Information System (INIS)

    Okada, Masaaki; Tanaka, Katsuyuki; Abe, Juzo; Sekino, Hiroaki; Ogawa, Takei; Hayashi, Tatsuo.

    1992-01-01

    Peritumoral edema associated with 28 meningiomas was studied. The results of radiological investigation, using MRI, CT, and angiography, and histological studies were described and correlated with each other in order to clarify the mechanism of peritumoral cerebral edema production. Extensive peritumoral edema was recognized when the venous sinus or cortical veins, especially the superficial and deep Sylvian veins, were invaded and/or compressed markedly by the tumor. Therefore, large tumors (more than 5 cm in diameter) which were located in the parasagittal area and the middle cranial fossa had a tendency to be associated with extensive peritumoral edema. The posterior fossa meningiomas were associated with small edema because there were rich venous channels in the posterior fossa. Although there have been several reports that the peritumoral edema of meningioma would be produced by the vessels of the tumor itself and would migrate through the tumor capsule into the surrounding brain tissue, and although mechanical factors alone are not sufficient to explain peritumoral edema production, we would like to postulate that the longstanding mechanical compression of venous circulation by the meningioma might be an important factor in the production of the peritumoral cerebral edema. (author)

  19. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. METHODS: We treated...... mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis...... by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation -- as measured by MRI and by dry/wet weight measurement of water content -- but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage...

  20. Cerebral edema in drug addicts

    Directory of Open Access Journals (Sweden)

    Daruši Dragana J.

    2014-01-01

    Full Text Available Background/Aim. The effect of drugs leaves permanent consequences on the brain, organic in type, followed by numerous manifestations, and it significantly affects the development of mental dysfunctions. The clinicians are often given a task to estimate a patient’s personality during treatment or during experts estimate of a drug addict. The aim of this research was to determine the differences, if any, in characteristics of addicts experience and personality traits in drug addicts with or without cerebral edema. Methods. The research was conducted on a sample of 252 male drug addicts, the average age of 23.3 (SD = 4.3 years. Cerebral edema was confirmed on magnetic resonance (MR images of the brain performed during the treatment of the addicts. The participants were tested by the psychologists using Minnesota Multiphasic Personality Inventory (MMPI-201 test, and the data were processed using canonical discriminate analysis within the SPSS program. The dependent variable in the study was cerebral edema. A block of independent variables, designed for the requirements of this study, consisted of two subgroups. The first one consisted of 12 variables describing the relevant characteristics of drug abuse. The second subgroup consisted of 8 psychopathological tendencies in the personality defined by the mentioned test. Results. Cerebral edema was confirmed in 52 (20.63% of the drug addicts. The differences between the groups of drug addicts with and without cerebral edema were determined in the following: the time span of taking drugs (0.301, use of alcohol parallel with drugs (0.466, and treatment for addiction (0.603. In the drug addicts with a cerebral edema, MMPI-201 confirmed the increase in the scales for hypochondria, psychopathic deviations and psychastenia, and the decrease in the scales for schizophrenia and depression. Conclusion. Our study confirmed a possible connection between cerebral edema and personality traits in a number of the

  1. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Chin-Yi Cheng

    2016-01-01

    Full Text Available Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs, including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

  2. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Sergey A Sosunov

    Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

  3. Histone deacetylases exert class specific roles in conditioning the brain and heart against acute ischemic injury.

    Directory of Open Access Journals (Sweden)

    Sverre Erik Aune

    2015-06-01

    Full Text Available Ischemia-reperfusion (IR injury comprises a significant portion of morbidity and mortality from heart and brain diseases worldwide. This enduring clinical problem has inspired myriad reports in the scientific literature of experimental interventions seeking to elucidate the pathology of IR injury. Elective cardiac surgery presents perhaps the most viable scenario for protecting the heart and brain from IR injury, due to the opportunity to condition the organs prior to insult. The physiological parameters for the preconditioning of vital organs prior to insult through mechanical and pharmacologic maneuvers have been heavily examined. These investigations have revealed new insights into how preconditioning alters cellular responses to IR injury. However, the promise of preconditioning remains unfulfilled at the clinical level, and research seeking to implicate cell signals essential to this protection continues. Recent discoveries in molecular biology have revealed that gene expression can be controlled through posttranslational modifications, without altering the chemical structure of the genetic code. In this scenario, gene expression is repressed by enzymes that cause chromatin compaction through catalytic removal of acetyl moieties from lysine residues on histones. These enzymes, called histone deacetylases (HDACs, can be inhibited pharmacologically, leading to the de-repression of protective genes. The discovery that HDACs can also alter the function of non-histone proteins through posttranslational deacetylation has expanded the potential impact of HDAC inhibitors for the treatment of human disease. HDAC inhibitors have been applied in a very small number of experimental models of IR. However, the scientific literature contains an increasing number of reports demonstrating that HDACs converge on preconditioning signals in the cell. This review will describe the influence of HDACs on major preconditioning signaling pathways in the heart and

  4. DNA array analysis of gene expression changes by Choto-san in the ischemic rat brain

    OpenAIRE

    Tohda, Michihisa; Matsumoto, Kinzo; Hayashi, Hisae; Murakami, Yukihisa; Watanabe, Hiroshi

    2004-01-01

    The effects of Choto-san on gene expression in the dementia model rat brain were studied using a DNA microarray system. Choto-san inhibited the expression of 181 genes that has been enhanced by permanent occlusion of the bilateral common carotid arteries (2VO). Choto-san also reversed the expression inhibition of 32 genes induced by 2VO. These results may suggest that Choto-san, which has been therapeutically used as an antidementive drug, shows therapeutic effects through gene expression cha...

  5. Quantitative analysis of brain metabolites concentrations using MR spectroscopy in acute hypoxia ischemic encephalopathy

    International Nuclear Information System (INIS)

    Xiao Yeyu; Wang HaiYu; Shen Zhiwei; Lin Yan; Chen Yaowen; Xiao Gang; Wu Renhua

    2010-01-01

    Objective: To evaluate the absolute quantification of brain metabolites concentrations using external standard MRS in acute hypoxia ischemia encephalopathy (HIE) piglet model. Method: Eight 7-day-old healthy piglets were subjected to insult of hypoxia ischemia (HI). The animals and an external standard phantom containing detectable metabolites of known concentrations were studied on a 1.5 T GE Signa scanner. The single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) data were processed using LCModel software, and the quantification of N-acetylaspartate (NAA), creatine (Cr) and lactate (Lac) were accomplished. Multivariate analysis of variance was performed to compare the NAA, Cr, Lac concentration differences in the brains of piglets pre- and post-HI (0h). In addition, the dynamic changes of brain metabolites concentrations of 2 HIE piglets were observed at the time points of 0 h and 2 h. Results: One piglet was excluded because it was over anesthetized to death. Seven piglets' data were analyzed. The concentrations of NAA pre- and post-HI were (6.86±0.49) mmol/kg and (5.73±0.88) mmol/kg respectively, they were (4.65±0.73) mmol/kg and (4.40±0.80) mmol/kg for Cr; and were 0.00 mmol/kg and (0.43±0.39) mmol/kg for Lac. After HI, decreased NAA concentration immediately was observed, and it was of statistical significance (F=8.608, P=0.013). The concentration of Cr was insignificantly decreased (F=0.379, P=0.550). The concentration of Lac was increased, and the difference was of statistical significance (F=8.600, P=0.013). Dynamic observation showed a Lac peak immediately after HI and it decreased after 2 h post-HI. Conclusions: External standard MRS using LCModel has great value in the quantitative analysis of brain metabolites. The changes of NAA and Lac concentrations are sensitive to reflect the early metabolic change of acute HIE. (authors)

  6. Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

    Science.gov (United States)

    Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

    2017-04-03

    Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Systemic right-to-left shunts, ischemic brain lesions, and persistent migraine activity.

    Science.gov (United States)

    Koppen, Hille; Palm-Meinders, Inge H; Mess, Werner H; Keunen, Ruud W; Terwindt, Gisela M; Launer, Lenore J; van Buchem, Mark A; Kruit, Mark C; Ferrari, Michel D

    2016-05-03

    To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1-3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2-4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3-5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8-3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2-10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9-9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine. © 2016 American Academy of Neurology.

  8. [Revelation of the circumstances of the accident vascular arterial ischemic brain in at term or near-term and referral].

    Science.gov (United States)

    Cneude, F; Diependaele, J-F; Chabernaud, J-L

    2017-09-01

    The neonatal arterial ischemic stroke is an emergency. Recurrent focal seizures, generally occurring in the first 24-72 hours after birth, are the commonest first clinical signs. When neonatal arterial ischemic stroke is suspected, optimal initial management involves careful supportive care including treatment of clinical and frequent or prolonged subclinical seizures, correction of the possible metabolic disorders and their prevention. Contrary to hypoxic ischemic encephalopathy, therapeutic hypothermia is not indicated. This newborn requires emergent transfer to a neonatal intensive care unit for the confirmation of the diagnosis by means of a specialized neonatal transport team. © 2017 Elsevier Masson SAS. Tous droits réservés.

  9. Protective Effect of Klotho against Ischemic Brain Injury Is Associated with Inhibition of RIG-I/NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Hong-Jing Zhou

    2018-01-01

    Full Text Available Aging is the greatest independent risk factor for the occurrence of stroke and poor outcomes, at least partially through progressive increases in oxidative stress and inflammation with advanced age. Klotho is an antiaging gene, the expression of which declines with age. Klotho may protect against neuronal oxidative damage that is induced by glutamate. The present study investigated the effects of Klotho overexpression and knockdown by an intracerebroventricular injection of a lentiviral vector that encoded murine Klotho (LV-KL or rat Klotho short-hairpin RNA (LV-KL shRNA on cerebral ischemia injury and the underlying anti-neuroinflammatory mechanism. The overexpression of Klotho induced by LV-KL significantly improved neurobehavioral deficits and increased the number of live neurons in the hippocampal CA1 and caudate putamen subregions 72 h after cerebral hypoperfusion that was induced by transient bilateral common carotid artery occlusion (2VO in mice. The overexpression of Klotho significantly decreased the immunoreactivity of glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1, the expression of retinoic-acid-inducible gene-I, the nuclear translocation of nuclear factor-κB, and the production of proinflammatory cytokines (tumor necrosis factor α and interleukin-6 in 2VO mice. The knockdown of Klotho mediated by LV-KL shRNA in the brain exacerbated neurological dysfunction and cerebral infarct after 22 h of reperfusion following 2 h middle cerebral artery occlusion in rats. These findings suggest that Klotho itself or enhancers of Klotho may compensate for its aging-related decline, thus providing a promising therapeutic approach for acute ischemic stroke during advanced age.

  10. A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury.

    Science.gov (United States)

    Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J David; Sahbaie, Peyman; Dill, David L; Peltz, Gary

    2016-05-01

    Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. Copyright © 2016 by the Genetics Society of America.

  11. BRAIN NATRIURETIC PEPTIDE (BNP: BIOMARKER FOR RISK STRATIFICATION AND FUNCTIONAL RECOVERY PREDICTION IN ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    STANESCU Ioana

    2015-02-01

    Full Text Available Functional outcome after cardiovascular and cerebrovascular events is traditionally predicted using demographic and clinical variables like age, gender, blood pressure, cholesterol levels, diabetes status, smoking habits or pre-existing morbidity. Identification of new variables will improve the risk stratification of specific categories of patients. Numerous blood-based biomarkers associated with increased cardiovascular risk have been identified; some of them even predict cardiovascular events. Investigators have tried to produce prediction models by incorporating traditional risk factors and biomarkers. (1. Widely-available, rapidly processed and less expensive biomarkers could be used in the future to guide management of complex cerebrovascular patients in order to maximize their recovery (2 Recently, studies have demonstrated that biomarkers can predict not only the risk for a specific clinical event, but also the risk of death of vascular cause and the functional outcome after cardiovascular or cerebrovascular events. Early prediction of fatal outcome after stroke may improve therapeutic strategies (such as the use of more aggressive treatments or inclusion of patients in clinical trials and guide decision-making processes in order to maximize patient’s chances for survival and recovery. (3 Long term functional outcome after stroke is one of the most difficult variables to predict. Elevated serum levels of brain natriuretic peptide (BNP are powerful predictor of outcomes in patients with cardiovascular disease (heart failure, atrial fibrillation. Potential role of BNP in predicting atrial fibrillation occurrence, cardio-embolic stroke and post-stroke mortality have been proved in many studies. However, data concerning the potential role of BNP in predicting short term and long term functional outcomes after stroke remain controversial.

  12. Side Effects: Edema (Swelling)

    Science.gov (United States)

    Edema is a condition in which fluid builds up in your body’s tissues. The swelling may be caused by chemotherapy, cancer, and conditions not related to cancer. Learn about signs of edema, including swelling in your feet, ankles, and legs.

  13. Approach to leg edema

    Directory of Open Access Journals (Sweden)

    Fulvio Pomero

    2017-09-01

    Full Text Available Edema is defined as a palpable swelling caused by an increase in interstitial fluid volume. Leg edema is a common problem with a wide range of possible causes and is the result of an imbalance in the filtration system between the capillary and interstitial spaces. Major causes of edema include venous obstruction, increased capillary permeability and increased plasma volume secondary to sodium and water retention. In both hospital and general practice, the patient with a swollen leg presents a common dilemma in diagnosis and treatment. The cause may be trivial or life-threatening and it is often difficult to determine the clinical pathway. The diagnosis can be narrowed by categorizing the edema according to its duration, distribution (unilateral or bilateral and accompanying symptoms. This work provides clinically oriented recommendations for the management of leg edema in adults.

  14. A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

    DEFF Research Database (Denmark)

    Bach, Anders*; Clausen, Bettina H; Møller, Magda

    2012-01-01

    Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are ...... of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke....

  15. 3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

    Science.gov (United States)

    Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

    2017-05-01

    Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    Energy Technology Data Exchange (ETDEWEB)

    Ancora, G. [Neonatal Intensive Care Unit, Department of Mother and Infant Infermi Hospital of Rimini, Rimini (Italy); Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R. [Department of Biomedical and Neuromotor Sciences University of Bologna, MR Functional Unit, Bologna (Italy); Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G. [University of Bologna, Neonatology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Tani, G. [University of Bologna, Radiology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Malucelli, E. [University of Bologna, Department of Pharmacy and Biotechnologies, Bologna (Italy)

    2013-08-15

    MRI, proton magnetic resonance spectroscopy ({sup 1}H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on {sup 1}H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and {sup 1}H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both {sup 1}H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of {sup 1}H-MRS and DTI, which outperform conventional MRI. (orig.)

  17. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    International Nuclear Information System (INIS)

    Ancora, G.; Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R.; Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G.; Tani, G.; Malucelli, E.

    2013-01-01

    MRI, proton magnetic resonance spectroscopy ( 1 H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on 1 H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and 1 H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both 1 H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of 1 H-MRS and DTI, which outperform conventional MRI. (orig.)

  18. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

    Science.gov (United States)

    Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

    2016-01-01

    Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

  19. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI mouse model. In this study, we investigated the potential of human MSCs (hMSCs to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6 or 2×10(6 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

  20. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

    Directory of Open Access Journals (Sweden)

    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  1. What Is Macular Edema?

    Medline Plus

    Full Text Available ... side) vision remains. Macular edema is often a complication of diabetic retinopathy , and is the most common form of vision loss for people with diabetes—particularly if it is left untreated. Next What ...

  2. Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

    Science.gov (United States)

    Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

    2017-04-01

    To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (pmemory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

  3. Edema: diagnosis and management.

    Science.gov (United States)

    Trayes, Kathryn P; Studdiford, James S; Pickle, Sarah; Tully, Amber S

    2013-07-15

    Edema is an accumulation of fluid in the interstitial space that occurs as the capillary filtration exceeds the limits of lymphatic drainage, producing noticeable clinical signs and symptoms. The rapid development of generalized pitting edema associated with systemic disease requires timely diagnosis and management. The chronic accumulation of edema in one or both lower extremities often indicates venous insufficiency, especially in the presence of dependent edema and hemosiderin deposition. Skin care is crucial in preventing skin breakdown and venous ulcers. Eczematous (stasis) dermatitis can be managed with emollients and topical steroid creams. Patients who have had deep venous thrombosis should wear compression stockings to prevent postthrombotic syndrome. If clinical suspicion for deep venous thrombosis remains high after negative results are noted on duplex ultrasonography, further investigation may include magnetic resonance venography to rule out pelvic or thigh proximal venous thrombosis or compression. Obstructive sleep apnea may cause bilateral leg edema even in the absence of pulmonary hypertension. Brawny, nonpitting skin with edema characterizes lymphedema, which can present in one or both lower extremities. Possible secondary causes of lymphedema include tumor, trauma, previous pelvic surgery, inguinal lymphadenectomy, and previous radiation therapy. Use of pneumatic compression devices or compression stockings may be helpful in these cases.

  4. Cystoid macular edema

    Directory of Open Access Journals (Sweden)

    Tryfon G Rotsos

    2008-10-01

    Full Text Available Tryfon G Rotsos1, Marilita M Moschos21Medical Retina Service, Moorfields Eye Hospital, London, UK; 2Department of Ophthalmology, University of Athens, GreeceAbstract: We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME. Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin, ranibizumab (Lucentis, pegaptamid (Macugen, and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice.Keywords: cystoid macular edema, anti-VEGF, fluoroangiography, OCT, multifocal electroretinography

  5. Effects of hypoxic–ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoyu; Cao Li; Guo Qiyong; Wang Xiaoming

    2011-01-01

    Introduction: Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic–ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ( 11 C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using 11 C-CFT PET. Methods: Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with 11 C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure. Results: A few minutes after intravenous injection of 11 C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P 11 C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P 11 C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.

  6. The Correlation Between a Short-term Conventional Electroencephalography in the First Day of Life and Brain Magnetic Resonance Imaging in Newborns Undergoing Hypothermia for Hypoxic-Ischemic Encephalopathy.

    Science.gov (United States)

    Obeid, Rawad; Sogawa, Yoshimi; Gedela, Satyanarayana; Naik, Monica; Lee, Vince; Telesco, Richard; Wisnowski, Jessica; Magill, Christine; Painter, Michael J; Panigrahy, Ashok

    2017-02-01

    Electroencephalograph recorded in the first day of life in newborns treated with hypothermia for hypoxic-ischemic encephalopathy could be utilized as a predictive tool for the severity of brain injury on magnetic resonance imaging and mortality. We analyzed newborns who were admitted for therapeutic hypothermia due to hypoxic-ischemic encephalopathy. All enrolled infants underwent encephalography within the first 24 hours of life and underwent brain magnetic resonance imaging after rewarming. All encephalographs were independently reviewed for background amplitude, continuity, and variability. Brain injury determined by magnetic resonance imaging was scored using methods described by Bonifacio et al. Forty-one newborns were included in the study. Each encephalograph variable correlated significantly with the severity of injury on brain magnetic resonance imaging (P encephalopathy correlated with the extent of injury on brain magnetic resonance imaging. This information may be useful for families and aid guide clinical decision making. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute ischemic stroke

    DEFF Research Database (Denmark)

    Sorensen, Sofie Solvsten; Nygaard, Ann-Britt; Carlsen, Anting Liu

    2017-01-01

    BackgroundThe purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation. MethodsCerebrospinal fluid (CSF) ...

  8. Tc99m-HMPAO Neuro--SPECT Assessment of Ischemic Penumbra in Acute Brain Infarct: Control of Intra-arterial Thrombolysis Treatment

    International Nuclear Information System (INIS)

    Mena, Francisco; Mena, Ismael; Ducci, Hector; Soto, Francisco; Pedraza, Luis; Contreras, Andrea; Miranda, Marcelo; Basaez, Esteban; Fruns, Manuel

    2004-01-01

    Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis, an approved therapy, if performed in the first 3 to 6 hours of evolution. Thrombolysis has many benefits, but it also has associated risks, mainly development of intracranial hemorrhage. The selection of which patient should receive this type of treatment had been an important research topic over the last decade. As a consequence neuroimaging of brain infarct has significantly improved during the last few years. A variety of diagnostic studies are now available in the evaluation of brain infarct and in particular of potentially reversible brain ischemia, including magnetic resonance imaging (MRI) diffusion-perfusion, perfusion computed tomography (CT) and functional neuroimaging techniques includes positron emission tomography (PET) and single-photon emission tomography (SPECT). The aim of this study is to present our experience with a group of patients that presented with acute brain ischemia and had a NeuroSPECT evaluation before and after intra-arterial thrombolysis and/or possible stent placement, in the treatment of acute brain infarct. Methods: 16 patients were treated acutely for a significant ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan performed to rule out hemorrhage or established infarct. 3) IV injection of 1100MBq Tc 99m HMPAO (Ceretec tm ) 4) Conventional cerebral angiography and intra-arterial thrombolysis with tPA and /or angioplasty/stent if necessary. 5) NeuroSPECT assessment of ischemic penumbra (Pre-therapy results). 6) 14 of 16 patients received a NeuroSPECT (Post-therapy results) control at 24 hours. NeuroSPECT image acquisition was performed immediately following arterial thrombolysis with a dual Head Camera, Siemens ECAM, SHR collimators and conventional protocol. Image processing was performed using the Neurogam, Segami Corp. Software as previously reported in Alasbimn Journal 2

  9. [Acute neurogenic pulmonary edema].

    Science.gov (United States)

    Roquefeuil, B

    1975-01-01

    Neurogenic edema, in the strict sense of the term, has at the present time practically not benefitted from precise hemodynamic investigations in human clinical practice, and owing to this fact, authors still classify them under the heading "mixed edema or of unknown pathogenesis". In contrast with this lack of information in man, animal experimental works are surprising by their coherence and the experimental facility of producing neurogenic edema (cranial hypertension by a small inflatable balloon and cisternal infection of fibrin). If one excludes the now ancient vagal theories (CAMERON 1949; CAMPBELL, 1949) which were never confirmed, all of the most recent experimental works (SARNOFF, 1952; DUCKER, 1968; LUISADA, 1967; MORITZ, 1974) confirm the adrenergic disorder of central origin during neurogenic A.P.E. which from the hemodynamic standpoint is like an authentic hemodynamic A.P.E. with raised left atrial pressure, pulmonary venous pressure and pulmonary capillary pressure.

  10. Malignant edema in swine

    OpenAIRE

    Pinto, Flávia Ferreira; Assis, Ronnie Antunes de; Lobato, Francisco Carlos Faria; Vargas, Agueda Castagna de; Barros, Ricardo Rocha; Gonçalves, Luciana Aramuni

    2005-01-01

    Edema maligno em suíno é uma infecção fatal da musculatura esquelética e tecido subcutâneo de ruminantes e outras espécies animais, causada principalmente por Clostridium septicum, embora possa ocorrer em associação com Clostridium chauvoei, Clostridium sordellii, Clostridium novyi tipo A e Clostridium perfringens tipo A. O diagnóstico efetivo do edema maligno deve levar em consideração, além dos dados clínicos e lesões de necropsia, os achados microscópicos, isolamento do agente, imunofluore...

  11. Microscopic study of edema in hydatidiform mole

    Directory of Open Access Journals (Sweden)

    Olivar C. Castejón

    2014-09-01

    Full Text Available Objectives: the purpose of this study is to use light microscopy and scanning electron microscopy to determine the effect of edema on the structure of the molar vesicle. Methods: samples were taken from the complete hydatidiform mole and processed using conventional light and scanning electron microscopy techniques and an observation protocol that identified four variables: factors underlying the development of edema; the condition of the trophoblast basement membrane, development of the villi, accumulation and degeneration of sulphated mucosubstances at stromal level. Results: light microscopy showed a permeable trophoblastic basement membrane, a swollen syncytium, edematous regions disorganizating the stromal region and causing ischemic necrosis of cells. Using scanning electron microscopy, the basement membrane was found to be distended and thickened, with large irregular holes for the entry and movement of liquid, leaving a wide range of fluids during the influx process and depriving stromal cells of nutrition. Conclusions: a new three-dimensional view of the changes brought about by the entry of fluids into the stroma of molar hydropic vesicles was provided by scanning electron microscopy and confirmed by light microscopy, thereby explaining the changes occurring at the level of the stroma as an effect of the edema.

  12. Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

    Science.gov (United States)

    Broocks, Gabriel; Flottmann, Fabian; Ernst, Marielle; Faizy, Tobias Djamsched; Minnerup, Jens; Siemonsen, Susanne; Fiehler, Jens; Kemmling, Andre

    2018-04-01

    Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001). Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging

  13. Pulmonary edema: radiographic differential diagnosis

    International Nuclear Information System (INIS)

    Yoo, Dong Soo; Choi, Young Hi; Kim, Seung Cheol; An, Ji Hyun; Lee, Jee Young; Park, Hee Hong

    1997-01-01

    To evaluate the feasibility of using chest radiography to differentiate between three different etiologies of pulmonary edema. Plain chest radiographs of 77 patients, who were clinically confirmed as having pulmonary edema, were retrospectively reviewed. The patients were classified into three groups : group 1 (cardiogenic edema : n = 35), group 2 (renal pulmonary edema : n = 16) and group 3 (permeability edema : n = 26). We analyzed the radiologic findings of air bronchogram, heart size, peribronchial cuffing, septal line, pleural effusion, vascular pedicle width, pulmonary blood flow distribution and distribution of pulmonary edema. In a search for radiologic findings which would help in the differentiation of these three etiologies, each finding was assessed. Cardiogenic and renal pulmonary edema showed overlapping radiologic findings, except for pulmonary blood flow distribution. In cardiogenic pulmonary edema (n=35), cardiomegaly (n=29), peribronchial cuffing (n=29), inverted pulmonary blood flow distribution (n=21) and basal distribution of edema (n=20) were common. In renal pulmonary edema (n=16), cardiomegaly (n=15), balanced blood flow distribution (n=12), and central (n=9) or basal distribution of edema (n=7) were common. Permeability edema (n=26) showed different findings. Air bronchogram (n=25), normal blood flow distribution (n=14) and peripheral distribution of edema (n=21) were frequent findings, while cardiomegaly (n=7), peribronchial cuffing (n=7) and septal line (n=5) were observed in only a few cases. On plain chest radiograph, permeability edema can be differentiated from cardiogenic or renal pulmonary edema. The radiographic findings which most reliably differentiated these two etiologies were air bronchogram, distribution of pulmonary edema, peribronchial cuffing and heart size. Only blood flow distribution was useful for radiographic differentiation of cardiogenic and renal edema

  14. What Is Macular Edema?

    Medline Plus

    Full Text Available ... for Diabetic Macular Edema Jul 17, 2015 Top 5 Risk Factors for AMD Jan 29, 2014 Is Your Laser Pointer Dangerous Enough to Cause Eye Injury? Dec 20, 2013 Study Finds Tablets Help People with Low Vision Nov 27, 2013 Follow The ...

  15. What Is Macular Edema?

    Medline Plus

    Full Text Available ... may be mild to severe, but in many cases, your peripheral (side) vision remains. Macular edema is often a complication of diabetic retinopathy , and is the most common form of vision loss for people with diabetes—particularly if it is left ... Studies Show Zika Virus May Cause More Serious Eye ...

  16. Latest advances in edema

    Science.gov (United States)

    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.

  17. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12 expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

    Directory of Open Access Journals (Sweden)

    Walker Aisha L

    2005-10-01

    Full Text Available Abstract Background Stromal cell-derived factor 1 (SDF-1 or CXCL12 is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI injury in neonatal brain. Results Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. Conclusion The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

  18. Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke.

    Science.gov (United States)

    Tan, Sha; Shan, Yilong; Wang, Yuge; Lin, Yinyao; Liao, Siyuan; Deng, Zhezhi; Zhou, Li; Cai, Wei; Zeng, Qin; Zhang, Lei; Zhang, Bingjun; Men, Xuejiao; Li, Haiyan; Hu, Xueqiang; Wu, Changyou; Peng, Lisheng; Lu, Zhengqi

    2017-07-01

    Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.

    Science.gov (United States)

    Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Moini, Ashraf; Ataeinejad, Nahid; Zendedel, Adib; Hassanzadeh, Gholamreza

    2017-02-01

    Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

  20. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Qiuhong Ji

    Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

  1. Insulin-like growth factor -1 (IGF-1) derived neuropeptides, a novel strategy for the development of pharmaceuticals for managing ischemic brain injury.

    Science.gov (United States)

    Guan, Jian

    2011-08-01

    Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective and improves long-term function after brain injury. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake, and mitogenic potential. Glycine-proline-glutamate (GPE) is naturally cleaved from the IGF-1 N-terminal and is also neuroprotective after ischemic injury, thus providing a potential novel strategy of drug discovery for management of neurological disorders. GPE is not enzymatically stable, thus intravenous infusion of GPE becomes necessary for stable and potent neuroprotection. The broad effective dose range and treatment window of 3-7 h after the lesion suggest its potential for treating acute brain injuries. The neuroprotective action of GPE is not age selective, is not dependent on cerebral reperfusion, plasma glucose concentrations, and core body temperature. G-2mPE, a GPE analogue designed to be more resistant to enzymatic activity, has a prolonged plasma half-life and is more potent in neuroprotection. Neuroprotection by GPE and its analogue may be involved in modulation of inflammation, promotion of astrocytosis, inhibition of apoptosis, and in vascular remodeling. Small neuropeptides have advantages over growth factors in the treatment of brain injury, and modified neuropeptides, designed to overcome the limitations of their endogenous counterparts, represent a novel strategy of pharmaceutical discovery for neurological disorders. © 2010 Blackwell Publishing Ltd.

  2. UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

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    M. Rasjad Indra

    2016-07-01

    Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

  3. Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    Science.gov (United States)

    Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

    2014-01-15

    The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

    Science.gov (United States)

    Kundrotiene, Jurgita; Wägner, Anna; Liljequist, Sture

    2004-01-01

    Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis. As assessed by daily beam walking tests it was shown that there was a spontaneous recovery of motor functions over a period of five to seven days after the ischemic event. Using histopathological analysis (Nissl staining) we have previously reported that the present experimental paradigm does not produce pannecrosis (tissue cavitation) despite the highly reproducible focal neurological deficit. We now show how staining with fluorescent markers for neuronal death, that is Fluoro-Jade and TUNEL, respectively, identifies regional patterns of selective neuronal death. These observations add further support to the working hypothesis that the brain damage caused by cortical compression-induced ischemia consists of scattered, degenerating neurons in specific brain regions. Postsurgical administration of the AMPA receptor specific antagonist, LY326325 (30 mg/kg; i.p., 70 min after compression), not only improved beam walking performance on day 1 to 3, respectively but also significantly reduced the number of Fluoro-Jade stained neurons on day 5. These results suggest that enhanced AMPA/glutamate receptor activity is at least partially responsible for the ischemia-produced brain damage detected by the fluorescent marker Fluoro-Jade.

  5. [Immersion pulmonary edema].

    Science.gov (United States)

    Desgraz, Benoît; Sartori, Claudio; Saubade, Mathieu; Héritier, Francis; Gabus, Vincent

    2017-07-12

    Immersion pulmonary edema may occur during scuba diving, snorke-ling or swimming. It is a rare and often recurrent disease, mainly affecting individuals aged over 50 with high blood pressure. However it also occurs in young individuals with a healthy heart. The main symptoms are dyspnea, cough and hemoptysis. The outcome is often favorable under oxygen treatment but deaths are reported. A cardiac and pulmonary assessment is necessary to evaluate the risk of recurrence and possible contraindications to immersion.

  6. Acute Idiopathic Scrotal Edema

    Directory of Open Access Journals (Sweden)

    Micheál Breen

    2013-01-01

    Full Text Available We report a case of acute idiopathic scrotal edema (AISE in a 4-year-old boy who presented with acute scrotal pain and erythema. The clinical features, ultrasound appearance, and natural history of this rare diagnosis are reviewed. In this report, we highlight the importance of good ultrasound technique in differentiating the etiology of the acute scrotum and demonstrate the color Doppler “Fountain Sign” that is highly suggestive of AISE.

  7. Analysis of peritumoral edema and contrast enhancement by computerized axial tomography

    International Nuclear Information System (INIS)

    Oi, Shizuo; Szper, I.; Wetzel, N.; Kim, Kwang-S.

    1980-01-01

    For the purpose of treating brain tumors satisfactorily with steroids, CT findings of brain tumors were analyzed, and pathogenesis of peritumoral edema and supposed effects of steroids were investigated. The degree of peritumoral edema and contrast enhancement and their relationship were analyzed in total 201 patients with brain tumors (gliomas, meningiomas, and metastatic brain tumors). As a result, significant peritumoral edema was recognized in 59% of patients with metastatic brain tumors, 46% of patients with glioma, and 34% of patients with meningioma. As a rule, there was a relationship between peritumoral edema and malignancy or localization of braiin tumors. Severe peritumoral edema was observed in malignant supratentorial tumors (over 60%), but peritumoral edema which was found in infratentorial tumors benign gliomas was mild. The degree of contrast enhancement differed according to tumors, and there was not always a relationship between the degree of contrast enhancement and malignancy or localization of brain tumors. CT findings of brain tumors after the administration of steroids showed decrease in the degree of contrast enhancement. Judging from the effect of steroids to inhibit increased vascular permeability associated with brain edema, like CT findings of peritumoral edema, the degree of contrast enhancement which probably expressed vascularity or vascular permeability seemed to be important in deciding the indications for steroid administration. (Tsunoda, M.)

  8. Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

    Science.gov (United States)

    Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

    2018-03-30

    Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle

  9. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    OpenAIRE

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program....

  10. Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio; Panigrahy, Ashok; Sreedher, Gayathri; Bailey, Ariel [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Laney, Ernest John [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Rush University Medical Center, Department of Diagnostic Radiology, Chicago, IL (United States); La Colla, Luca [University of Parma, Department of Anesthesiology, Parma (Italy); UPMC Shadyside Hospital, Department of Emergency Medicine, Pittsburgh, PA (United States); Alper, Gulay [Children' s Hospital of Pittsburgh of UPMC, Department of Pediatric Neurology, Neuroimmunology Clinic, Pittsburgh, PA (United States)

    2014-08-15

    MR imaging criteria for diagnosing acute disseminated encephalomyelitis (ADEM) have not been clearly established. Due to the wide spectrum of differential considerations, new imaging features allowing early and accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would be characterized by vasogenic edema due to the potential reversibility of the disease. Sixteen patients who met the diagnostic criteria for ADEM proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) and had complete MR imaging studies performed at our institution during the acute phase of the disease were identified retrospectively and evaluated by experienced pediatric neuroradiologists. Vasogenic edema was demonstrated on diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two patients while the other two patients displayed no changes on DWI/ADC. ADC values for lesions and normal-appearing brain tissue were 1.39 ± 0.45 x 10{sup -3} and 0.81 ± 0.09 x 10{sup -3} mm/s{sup 2}, respectively (p = 0.002). When considering a cutoff of 5 days between acute and subacute disease, no difference between ADC values in acute vs. subacute phase was depicted. However, we found a significant correlation and an inverse and significant relationship between time and ADC value. We propose that vasogenic edema is a reliable diagnostic sign of acute neuroinflammation in ADEM. (orig.)

  11. Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis

    International Nuclear Information System (INIS)

    Zuccoli, Giulio; Panigrahy, Ashok; Sreedher, Gayathri; Bailey, Ariel; Laney, Ernest John; La Colla, Luca; Alper, Gulay

    2014-01-01

    MR imaging criteria for diagnosing acute disseminated encephalomyelitis (ADEM) have not been clearly established. Due to the wide spectrum of differential considerations, new imaging features allowing early and accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would be characterized by vasogenic edema due to the potential reversibility of the disease. Sixteen patients who met the diagnostic criteria for ADEM proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) and had complete MR imaging studies performed at our institution during the acute phase of the disease were identified retrospectively and evaluated by experienced pediatric neuroradiologists. Vasogenic edema was demonstrated on diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two patients while the other two patients displayed no changes on DWI/ADC. ADC values for lesions and normal-appearing brain tissue were 1.39 ± 0.45 x 10 -3 and 0.81 ± 0.09 x 10 -3 mm/s 2 , respectively (p = 0.002). When considering a cutoff of 5 days between acute and subacute disease, no difference between ADC values in acute vs. subacute phase was depicted. However, we found a significant correlation and an inverse and significant relationship between time and ADC value. We propose that vasogenic edema is a reliable diagnostic sign of acute neuroinflammation in ADEM. (orig.)

  12. Edema pulmonar neurogênico: relato de dois casos Neurogenic pulmonary edema: report of two cases

    Directory of Open Access Journals (Sweden)

    Desanka Dragosavac

    1997-06-01

    Full Text Available O edema pulmonar neurogênico é rara e grave complicação de pacientes com traumatismo craniencefálico (TCE. Pode ocorrer também em outras patologias do sistema nervoso central, tais como acidentes vasculares cerebrais (AVC, tumores ou após crises epilépticas, entre outras. Foram avaliados 36 casos com TCE grave e quatro pacientes com AVC, internados na UTI geral, no período de janeiro a setembro 1995. Nesse intervalo de tempo foram diagnosticados dois casos de edema pulmonar neurogênico, um ocorrendo em paciente com TCE grave e outro em paciente com AVC hemorrágico. O diagnóstico foi estabelecido pelo rápido desenvolvimento de edema pulmonar, com hipoxemia grave, queda da complacência pulmonar e infiltrados difusos bilaterais sem história prévia de aspiração traqueal ou outro fator de risco para o desenvolvimento de síndrome de angústia respiratória aguda. No primeiro paciente com trauma craniencefálico, o edema neurogênico foi diagnosticado na internação, uma hora após o trauma, com concomitante reação inflamatória grave e boa evolução em três dias. O outro caso, com AVC hemorrágico, desenvolveu edema neurogênico no quarto dia após drenagem de hematoma intraparenquimatoso, evoluindo para o óbito.Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal

  13. Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

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    En-ping Jiang

    2011-06-01

    Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

  14. Endothelial Cells and Astrocytes: A Concerto en Duo in Ischemic Pathophysiology

    Directory of Open Access Journals (Sweden)

    Vincent Berezowski

    2012-01-01

    Full Text Available The neurovascular/gliovascular unit has recently gained increased attention in cerebral ischemic research, especially regarding the cellular and molecular changes that occur in astrocytes and endothelial cells. In this paper we summarize the recent knowledge of these changes in association with edema formation, interactions with the basal lamina, and blood-brain barrier dysfunctions. We also review the involvement of astrocytes and endothelial cells with recombinant tissue plasminogen activator, which is the only FDA-approved thrombolytic drug after stroke. However, it has a narrow therapeutic time window and serious clinical side effects. Lastly, we provide alternative therapeutic targets for future ischemia drug developments such as peroxisome proliferator- activated receptors and inhibitors of the c-Jun N-terminal kinase pathway. Targeting the neurovascular unit to protect the blood-brain barrier instead of a classical neuron-centric approach in the development of neuroprotective drugs may result in improved clinical outcomes after stroke.

  15. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  16. CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Rovira, Alex [University Hospital Vall d' Hebron, MR Unit, Department of Radiology, Barcelona (Spain); Costa Leite, Claudia da [Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil); Lucato, Leandro Tavares [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil)

    2010-11-15

    Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

  17. CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

    International Nuclear Information System (INIS)

    Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi; Rovira, Alex; Costa Leite, Claudia da; Lucato, Leandro Tavares

    2010-01-01

    Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

  18. Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice.

    Science.gov (United States)

    Chien, Mei-Yin; Chuang, Cheng-Hung; Chern, Chang-Ming; Liou, Kou-Tong; Liu, Der-Zen; Hou, Yu-Chang; Shen, Yuh-Chiang

    2016-10-01

    Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Aneurysmal wall enhancement and perianeurysmal edema after endovascular treatment of unruptured cerebral aneurysms

    International Nuclear Information System (INIS)

    Su, I. Chang; Willinsky, Robert A.; Agid, Ronit; Fanning, Noel F.

    2014-01-01

    Perianeurysmal edema and aneurysm wall enhancement are previously described phenomenon after coil embolization attributed to inflammatory reaction. We aimed to demonstrate the prevalence and natural course of these phenomena in unruptured aneurysms after endovascular treatment and to identify factors that contributed to their development. We performed a retrospective analysis of consecutively treated unruptured aneurysms between January 2000 and December 2011. The presence and evolution of wall enhancement and perianeurysmal edema on MRI after endovascular treatment were analyzed. Variable factors were compared among aneurysms with and without edema. One hundred thirty-two unruptured aneurysms in 124 patients underwent endovascular treatment. Eighty-five (64.4 %) aneurysms had wall enhancement, and 9 (6.8 %) aneurysms had perianeurysmal brain edema. Wall enhancement tends to persist for years with two patterns identified. Larger aneurysms and brain-embedded aneurysms were significantly associated with wall enhancement. In all edema cases, the aneurysms were embedded within the brain and had wall enhancement. Progressive thickening of wall enhancement was significantly associated with edema. Edema can be symptomatic when in eloquent brain and stabilizes or resolves over the years. Our study demonstrates the prevalence and some appreciation of the natural history of aneurysmal wall enhancement and perianeurysmal brain edema following endovascular treatment of unruptured aneurysms. Aneurysmal wall enhancement is a common phenomenon while perianeurysmal edema is rare. These phenomena are likely related to the presence of inflammatory reaction near the aneurysmal wall. Both phenomena are usually asymptomatic and self-limited, and prophylactic treatment is not recommended. (orig.)

  20. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

    OpenAIRE

    Schober, Michelle E.; Requena, Daniela F.; Abdullah, Osama M.; Casper, T. Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R.

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimen...

  1. CT findings and prognosis of 70 full-term infants having spasm due to hypoxic ischemic encephalography following asphyxia

    International Nuclear Information System (INIS)

    Ogita, Yasutoki; Kawakami, Tadashi; Tsunei, Mikio; Ohta, Yuko; Sone, Yoshiharu; Akamatsu, Hiroshi

    1984-01-01

    Relationship between cranial CT findings and prognosis at 12 months or more after birth was studied in 70 full-term (appropriate for date and large for date) infants who had spasm due to hypoxic ischemic encephalopathy following neonatal asphyxia. There was correlation between the prognosis of the infants and neonatal CT findings showing slight and marked low density areas in the brain parenchyma. However, it was sometimes difficult to estimate the prognosis when the low density area was moderate on CT. Therefore, follow-up CT at one and six months and one year after birth was required to examine changes in low density areas for the estimation of prognosis. The prognosis was unfavorable in cases of the disease accompanied by hemorrhage in the brain parenchyma or cerebral ventricle, persistent cerebral edema on neonatal CT, and low density areas in the atrophied brain by the follow-up CT. There was no consistent relationship between subarachnoid hemorrhage and the prognosis. (Namekawa, K.)

  2. Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping

    OpenAIRE

    Gonzalez-Brito Manuel; Solano Juan; Sanchez Pablo; Georgiou Michael F; Capille Michael; McGoron Anthony J; Kuluz John W

    2008-01-01

    Abstract Background Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. Me...

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

    Science.gov (United States)

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

    2014-07-11

    Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); pbeam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Diabetic Macular Edema.

    Science.gov (United States)

    Gundogan, Fatih C; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

    2016-01-01

    Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article.

  5. [Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

    Science.gov (United States)

    Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

    2014-01-01

    Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

  6. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

    2015-01-01

    Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574

  7. Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

    Science.gov (United States)

    Gao, Jie; Sun, Qin-Li; Zhang, Yu-Miao; Li, Yan-Yan; Li, Huan; Hou, Xin; Yu, Bo-Lang; Zhou, Xi-Hui; Yang, Jian

    2015-01-01

    Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes

  8. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M

    1983-01-01

    ). Autoregulation was impaired in all of the collaterally perfused areas while the CO2-response always was preserved. Steal phenomena were not seen. In the surrounding brain tissue, autoregulation was normal in 5 patients and impaired in 3 while the CO2-response seemed to be normal. The results confirm...

  9. Bone marrow edema syndrome

    International Nuclear Information System (INIS)

    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E.; Karantanas, Apostolos H.

    2009-01-01

    Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged males. Many hypotheses have been proposed to explain the pathogenesis of the disease. Unfortunately, the etiology of BMES remains obscure. The hallmark that separates BMES from other conditions presented with BME pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Histological examination of the lesion is unnecessary. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is mainly used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are spontaneously resolving, and surgical treatment is not needed. On the other hand, early differential diagnosis and surgical treatment in case of osteonecrosis is of crucial importance. (orig.)

  10. 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.

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    Full Text Available 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-1β. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1β 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-1β, 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.

  11. Acute ischemic stroke prognostication, comparison between ...

    African Journals Online (AJOL)

    Ossama Y. Mansour

    2014-11-20

    Nov 20, 2014 ... patients with acute ischemic stroke in comparison with the NIHSS and the GCS. Methods: .... All patients received a CT scan of the brain on admission. Diagnostic ... adjusted for age, sex, Charlson Index and Oxfordshire. 248.

  12. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

    Directory of Open Access Journals (Sweden)

    Lou Yongli

    2016-01-01

    Full Text Available In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were administered intranasally to nine day old mice, and analyzed by MRI at day 28. Results indicate that the MSCs, especially the hanging drop cultured MSCs, significantly improved the mice’s cerebellar damage repair. MSCs derived from the hanging drop culture were smaller than those from the conventional culture. The gene expression levels were significantly increased for the MSCs derived from the hanging drop culture. The mechanism might relate to the fact that the hanging drop cultured MSCs can be kept in an undifferentiated state, resulting in its higher expression level of migration receptor of CXCR4.

  13. Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Min Guo

    2018-03-01

    Full Text Available Background: Neuroprotective effects of ketogenic diets (KD have been reported in stroke models, and nucleotide-binding domain (NOD-like receptor protein 3 (NLRP3 inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms.Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB followed by oxygen–glucose deprivation/reoxygenation (OGD/R. NLRP3 inflammasome activation and related regulatory mechanisms were evaluated.Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1 to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation.Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke.

  14. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-02-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

  15. Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte.

    Science.gov (United States)

    Gu, Yan; He, Mulan; Zhou, Xiaoqin; Liu, Jinngjing; Hou, Nali; Bin, Tan; Zhang, Yun; Li, Tingyu; Chen, Jie

    2016-01-14

    Mesenchymal stem cell (MSC) transplantation reduces the neurological impairment caused by hypoxic-ischemic brain damage (HIBD) via immunomodulation. In the current study, we found that MSC transplantation improved learning and memory function and enhanced long-term potentiation in neonatal rats subjected to HIBD and the amount of IL-6 released from MSCs was far greater than that of other cytokines. However, the neuroprotective effect of MSCs infected with siIL-6-transduced recombinant lentivirus (siIL-6 MSCs) was significantly weakened in the behavioural tests and electrophysiological analysis. Meanwhile, the hippocampal IL-6 levels were decreased following siIL-6 MSC transplantation. In vitro, the levels of IL-6 release and the levels of IL-6R and STAT3 expression were increased in both primary neurons and astrocytes subjected to oxygen and glucose deprivation (OGD) following MSCs co-culture. The anti-apoptotic protein Bcl-2 was upregulated and the pro-apoptotic protein Bax was downregulated in OGD-injured astrocytes co-cultured with MSCs. However, the siIL-6 MSCs suppressed ratio of Bcl-2/Bax in the injured astrocytes and induced apoptosis number of the injured astrocytes. Taken together, these data suggest that the neuroprotective effect of MSC transplantation in neonatal HIBD rats is partly mediated by IL-6 to enhance anti-apoptosis of injured astrocytes via the IL-6/STAT3 signaling pathway.

  16. Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

    Science.gov (United States)

    Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

    2016-06-01

    The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

  17. Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

    Science.gov (United States)

    Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

    2017-09-01

    Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke

    Directory of Open Access Journals (Sweden)

    Petterson Jodie

    2010-02-01

    Full Text Available Abstract 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 1 stroke -Δ 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

  19. Immature rat brain slices exposed to oxygen-glucose deprivation as an in vitro model of neonatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Fernández-López, David; Martínez-Orgado, José; Casanova, Ignacio; Bonet, Bartolomé; Leza, Juan Carlos; Lorenzo, Pedro; Moro, Maria Angeles; Lizasoain, Ignacio

    2005-06-30

    To analyze whether exposure to oxygen-glucose deprivation (OGD) of immature rat brain slices might reproduce the main pathophysiologic events leading to neuronal death in neonatal hypoxic-ischemic encephalopathy (NHIE), 500 microm-thick brain slices were obtained from 7-day-old Wistar rats, and incubated in oxygenated physiological solution. In OGD group, oxygen and glucose were removed from the medium for 10-30 min (n = 25); then, slices were re-incubated in normal medium. In control group the medium composition remained unchanged (CG, n = 30). Medium samples were obtained every 30 min for 3 h. To analyze neuronal damage, slices were stained with Nissl and CA1 area of hippocampus and cortex were observed under microscopy. In addition, neuronal death was quantified as LDH released to the medium determined by spectrophotometry. Additionally, medium glutamate (Glu) levels were determined by HPLC and those of TNFalpha by ELISA, whereas inducible nitric oxide synthase expression was determined by Western blot performed on slices homogenate. Optimal OGD time was established in 20 min. After OGD, a significant decrease in the number of neurones in hippocampus and cortex was observed. LDH release was maximal at 30 min, when it was five-fold greater than in CG. Furthermore, medium Glu concentrations were 200 times greater than CG levels at the end of OGD period. A linear relationship between Glu and LDH release was demonstrated. Finally, 3 h after OGD a significant induction of iNOS as well as an increase in TNFalpha release were observed. In conclusion, OGD appears as a feasible and reproducible in vitro model, leading to a neuronal damage, which is physiopathologically similar to that found in NHIE.

  20. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-01-01

    including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

  1. Role of neuroinflammation in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

    2017-01-01

    Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

  2. Cerebrolysin and aquaporin 4 inhibition improve pathological and motor recovery after ischemic stroke.

    Science.gov (United States)

    Catalin, Bogdan; Rogoveanu, O C; Pirici, Ionica; Balseanu, Tudor Adrian; Stan, Adina; Tudorica, Valerica; Balea, Maria; Mindrila, Ion; Albu, Carmen Valeria; Mohamed, Guleed; Pirici, Daniel; Muresanu, Dafin Fior

    2018-04-25

    Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronal-survival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. Our data shows that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

    Science.gov (United States)

    Sáez-Llorens, X; Jafari, H S; Severien, C; Parras, F; Olsen, K D; Hansen, E J; Singer, I I; McCracken, G H

    1991-12-01

    Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

  4. Peculiarities of reaction of HIF-1α protein of the hippocampus neurons in rats with experimental diabetes mellitus in the dynamics of ischemic-reperfusion damage of the brain

    Directory of Open Access Journals (Sweden)

    T. M. Boychuk

    2016-12-01

    Higher State Educational Establishment of Ukraine “Bukovinian State medical University”, Chernivtsi, Ukraine   Abstract Introduction. The role of the transcriptional factor Hif-1α in pathogenesis of hypoxic damages and diabetes mellitus (DM is proved, although molecular mechanisms underlying the basis of this factor dysfunction in association with DM with ischemic-reperfusion damage of the brain remain unknown. Objective. The objective of this investigation was to study the content of Hif-1α protein in the hippocampus neurons of rats with experimental DM in the dynamics of ischemic-reperfusion damage of the brain. Results. In rats without DM 20 minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the fields of the hippocampus. On the 12th day of ischemic-reperfusion period in the hippocampus CA2-CA4 fields the values of certain examined indices of the activity of Hif-1α transcriptional factor continue to increase, and in СА1field they normalize or approach to the values of animals in the control group.  In rats with DM during early post-ischemic period there are no changes of Hif-1α protein content in CA1 field, in CA2 field there are signs of its reduced activity, in CA3 field they are limited by the reaction of one index, in CA4 field they are of a similar character with those of the control rats under experimental conditions.  On the 12th day of ischemic-reperfusion period in CA1 field all the indices of activity of Hif-1α transcriptional factor increase exceeding corresponding indices by absolute values in animals of the control group under the same experimental conditions, in СА2 and СА3 fields changes of the examined parameters are limited as compared to the same ones in animals from the control group, in CA4 field values that were increased in the control group decrease. Conclusions. Diabetes mellitus restricts reaction of Hif-1α protein on ischemia-reperfusion inn the neurons of СА1-СА3 fields in

  5. Recent Trends in Neuro-endovascular Treatment for Acute Ischemic Stroke, Cerebral Aneurysms, Carotid Stenosis, and Brain Arteriovenous Malformations.

    Science.gov (United States)

    Matsumaru, Yuji; Ishikawa, Eiichi; Yamamoto, Tetsuya; Matsumura, Akira

    2017-06-15

    The efficacy of mechanical thrombectomy with stent retrievers for emergent large vessel occlusion has been proved by randomized trials. Mechanical thrombectomy is increasingly being adopted in Japan since stent retrievers were first approved in 2014. An urgent clinical task is to offer structured systems of care to provide this treatment in a timely fashion to all patients with emergent large vessel occlusion. Treatment with flow-diverting stents is currently a preferred treatment option worldwide for large and giant unruptured aneurysms. Initial studies reported high rates of complete aneurysm occlusion, even in large and giant aneurysms, without delayed aneurysmal recanalization and/or growth. The Pipeline Embolic Device is a flow diverter recently approved in Japan for the treatment of large and giant wide-neck unruptured aneurysms in the internal carotid artery, from the petrous to superior hypophyseal segments. Carotid artery stenting is the preferred treatment approach for carotid stenosis in Japan, whereas it remains an alternative for carotid endarterectomy in Europe and the United States. Carotid artery stenting with embolic protection and plaque imaging is effective in achieving favorable outcomes. The design and conclusions of a randomized trial of unruptured brain arteriovenous malformations (ARUBA) trial, which compared medical management alone and medical management with interventional therapy in patients with an unruptured arteriovenous brain malformation, are controversial. However, the annual bleeding rate (2.2%) of the medical management group obtained from this study is worthy of consideration when deciding treatment strategy.

  6. Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism.

    Science.gov (United States)

    Lu, Qing; Harris, Valerie A; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Black, Stephen M

    2015-12-01

    We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the objective of this study was to determine if there was a role for the hydroxyl radical in neonatal HI brain injury and to elucidate the underlying mechanisms. Our data demonstrate that HI increases the deposition of free iron and hydroxyl radical formation, in both P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these processes were found to be nitric oxide (NO) dependent. Further analysis demonstrated that the NO-dependent increase in iron deposition was mediated through increased transferrin receptor expression and a decrease in ferritin expression. This was correlated with a reduction in aconitase activity. Both NO inhibition and iron scavenging, using deferoxamine administration, reduced hydroxyl radical levels and neuronal cell death. In conclusion, our results suggest that increased NO generation leads to neuronal cell death during neonatal HI, at least in part, by altering iron homeostasis and hydroxyl radical generation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Diagnosis of ischemic cerebrovascular diseases with 99mTc-HMPAO brain SPECT using upright stress test

    International Nuclear Information System (INIS)

    Chen Shaoliang; Xiu Yan; Sun Xiaoguang

    1998-01-01

    Purpose: To evaluate the value of upright brain SPECT stress test, the authors performed 99m Tc-HMPAO brain SPECT in association with measurement of blood pressure in both upright and supine positions. Methods: The authors studied 5 patients with unilateral stenosis occlusion of the internal carotid (Group A), 8 patients with orthostatic hypotension (group B) and 7 normal controls. 370 MBq 99m Tc-HMPAO was injected immediately after uprighting from a supine position. then the first SPECT scan were performed. After the first SPECT, another 555 MBq of 99m Tc-HMPAO were administered while the patients remained on original supine position. Results: Semiquantitive analysis showed that the asymmetric ratios between upright and supine positions in group A changed significantly. In group B, showed postural cerebral hypoperfusion in the bilateral frontal areas, the mean count ratio of the frontal to cerebellar area between the upright and supine positions also significantly changed. In the normal group, there were no significantly changes during the upright test. Conclusions: The upright stress test is useful for detecting not only silent cerebral hypoperfusion, but also orthostatic hypoperfusion

  8. Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.

    Science.gov (United States)

    Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Kim, Ji An; Hwang, Jung Soon; Sohn, Eun Jeong; Jeong, Ji-Heon; Kim, Duk-Soo; Kwon, Hyeok Yil; Cho, Yong-Jun; Lee, Keunwook; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2016-08-01

    Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H2O2 and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H2O2 treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3σ complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CA1 region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Association of degree and type of edema in posterior reversible encephalopathy syndrome with serum lactate dehydrogenase level: Initial experience

    International Nuclear Information System (INIS)

    Gao, Bo; Liu, Feng-li; Zhao, Bin

    2012-01-01

    Purpose: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity characterized by headache, blurred vision and seizures with typical parieto-occipital predominantly vasogenic edema, occasionally with cytotoxic edema. The association between the degree and type of edema in PRES with biochemical parameter, especially serum lactate dehydrogenase, has not been determined. Material and methods: Thirty-five patients with typical clinical symptoms and characteristic MR imaging findings of PRES were included in this study. The extent of brain edema was graded on the anatomical distribution by 2 observers blinded to patients’ clinical record, as well as the type of brain edema determined on DWI and ADC map. The levels of biochemical parameters were correlated with the degree of edema and compared between different types of edema. Results: Serum LDH concentrations between patients with cytotoxic edema and with vasogenic components were not statistically different (NWU test, U = 93.0, Z = 1.818, P = 0.069). Only serum lactate dehydrogenase (LDH) concentration was significantly correlated with the score of brain edema distribution (Spearman's rho correlation, r = 0.721, P = 0.00). No relationship was found between other biochemical parameters and the degree and type of brain edema. Conclusion: Increased serum LDH level, which plays an essential role in endothelial injury, may be a potential risk factor for the development of edema in PRES

  10. Association of degree and type of edema in posterior reversible encephalopathy syndrome with serum lactate dehydrogenase level: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Bo, E-mail: gygb2004@yahoo.com.cn [Shandong Medical Imaging Research Institute, Medical School of Shandong University, Jinan, Shandong 250021 (China); Division of MRI, Department of Radiology, Yantai Yuhuangding Hospital, Yantai, 264000 Shandong (China); Liu, Feng-li [Division of MRI, Department of Radiology, Yantai Yuhuangding Hospital, Yantai, 264000 Shandong (China); Zhao, Bin, E-mail: cjr.zhaobin@vip.163.com [Shandong Medical Imaging Research Institute, Medical School of Shandong University, Jinan, Shandong 250021 (China)

    2012-10-15

    Purpose: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity characterized by headache, blurred vision and seizures with typical parieto-occipital predominantly vasogenic edema, occasionally with cytotoxic edema. The association between the degree and type of edema in PRES with biochemical parameter, especially serum lactate dehydrogenase, has not been determined. Material and methods: Thirty-five patients with typical clinical symptoms and characteristic MR imaging findings of PRES were included in this study. The extent of brain edema was graded on the anatomical distribution by 2 observers blinded to patients’ clinical record, as well as the type of brain edema determined on DWI and ADC map. The levels of biochemical parameters were correlated with the degree of edema and compared between different types of edema. Results: Serum LDH concentrations between patients with cytotoxic edema and with vasogenic components were not statistically different (NWU test, U = 93.0, Z = 1.818, P = 0.069). Only serum lactate dehydrogenase (LDH) concentration was significantly correlated with the score of brain edema distribution (Spearman's rho correlation, r = 0.721, P = 0.00). No relationship was found between other biochemical parameters and the degree and type of brain edema. Conclusion: Increased serum LDH level, which plays an essential role in endothelial injury, may be a potential risk factor for the development of edema in PRES.

  11. Non-invasive Continuous Monitoring of Cerebral Edema Using Portable Microwave Based System

    Science.gov (United States)

    Jiang, Yuhao; Zhao, Minji; Wang, Huiqian; Li, Guoquan

    2018-01-01

    A portable non-invasive head detecting system based on microwave technology was developed for evaluation of cerebral edema change inside human brain. Real-time monitoring of cerebral edema in the brain helps the clinician to assess medical condition and treatment. In this work, a microwave signal was transmitted and coupled into an open-end circular waveguide sensor, incident on a 3D printed head phantom, and reflected back to receiver. Theoretically, the operation of this instrument depends on the conductivity contrast between cerebral edema and healthy brain tissues. The efficacy of the proposed detecting system is verified using 3D printed anatomically and dielectrically realistic human head phantoms with simulated cerebral edema targets with different size. Changes in the amplitude of time domain result were shown to be induced by the expansion or decrease of the edema volume. The eventual goal of this proposed head evaluating system is use in the hospital as an effective real-time monitoring tool.

  12. What Is Macular Edema?

    Medline Plus

    Full Text Available ... brain and interpreted as the images you see. It is the macula that is responsible for your ... fluids. The macula does not function properly when it is swollen. Vision loss may be mild to ...

  13. Embryonic Stem Cell-Derived Mesenchymal Stem Cells (MSCs) Have a Superior Neuroprotective Capacity Over Fetal MSCs in the Hypoxic-Ischemic Mouse Brain.

    Science.gov (United States)

    Hawkins, Kate E; Corcelli, Michelangelo; Dowding, Kate; Ranzoni, Anna M; Vlahova, Filipa; Hau, Kwan-Leong; Hunjan, Avina; Peebles, Donald; Gressens, Pierre; Hagberg, Henrik; de Coppi, Paolo; Hristova, Mariya; Guillot, Pascale V

    2018-05-01

    Human mesenchymal stem cells (MSCs) have huge potential for regenerative medicine. In particular, the use of pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) overcomes the hurdle of replicative senescence associated with the in vitro expansion of primary cells and has increased therapeutic benefits in comparison to the use of various adult sources of MSCs in a wide range of animal disease models. On the other hand, fetal MSCs exhibit faster growth kinetics and possess longer telomeres and a wider differentiation potential than adult MSCs. Here, for the first time, we compare the therapeutic potential of PSC-MSCs (ES-MSCs from embryonic stem cells) to fetal MSCs (AF-MSCs from the amniotic fluid), demonstrating that ES-MSCs have a superior neuroprotective potential over AF-MSCs in the mouse brain following hypoxia-ischemia. Further, we demonstrate that nuclear factor (NF)-κB-stimulated interleukin (IL)-13 production contributes to an increased in vitro anti-inflammatory potential of ES-MSC-conditioned medium (CM) over AF-MSC-CM, thus suggesting a potential mechanism for this observation. Moreover, we show that induced pluripotent stem cell-derived MSCs (iMSCs) exhibit many similarities to ES-MSCs, including enhanced NF-κB signaling and IL-13 production in comparison to AF-MSCs. Future studies should assess whether iMSCs also exhibit similar neuroprotective potential to ES-MSCs, thus presenting a potential strategy to overcome the ethical issues associated with the use of embryonic stem cells and providing a potential source of cells for autologous use against neonatal hypoxic-ischemic encephalopathy in humans. Stem Cells Translational Medicine 2018;7:439-449. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  14. [Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Li, Xiao-Li; Jia, Tian-Ming; Luan, Bin; Liu, Tao; Yuan, Yan

    2011-04-01

    To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.

  15. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    Directory of Open Access Journals (Sweden)

    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  16. Correction of the acid-base balance in the presence of the hypoxic-ischemic brain damage in newborns

    Directory of Open Access Journals (Sweden)

    K. S. Kiriakov

    2018-01-01

    Full Text Available One of the current problems of perinatal neurology is the hypoxic-ischemic brain damage in newborns associated with the influence of the hypoxia upon the fetus, intranatal and postnatal asphyxia on one hand and a lack of the efficient therapy schemes on the other hand. Due to this, the purpose of this pilotstudy isto identify the effects of drug Cytoflavin, included into the complex therapy scheme for the newborns with the cerebral ischemia of II-III stages, on the blood acid-base balance. A retrospective analysis of the results of the complex therapy for 16 newborns with the moderate (14 children and severe (2 children brain ischemia was performed. Cytoflavin was included in the standard therapy schemes for all children at a dose of 2 ml/kg per day at a dilution of 5% glucose solution at the ratio of 1:5, intravenously, microfluidically for 20 hours for 3 days. In addition to the standard examination, the blood acid-base balance assessment using the follow-up microgasometric method was included (after 60 min and then every 6 hours until 72 hours of observation. All children had positive tendency to the arresting of the metabolic acidosis (in the form of the decrease of the base deficiency after 24 hours and increase of pH level (the level of 7.30 was reached by 12 hours of age in full-term newborns and 24 hour of age in the preterm newborns. The revealed positive changes in the time of the metabolic acidosis arresting along with the small volumes of the infusion and good tolerability are the cause for the planning of the subsequent, more large-scale studies. 

  17. Etiopathogenesis of neurogenic pulmonary edema

    Czech Academy of Sciences Publication Activity Database

    Šedý, Jiří

    2010-01-01

    Roč. 160, 5-6 (2010), s. 152-154 ISSN 0043-5341 Institutional research plan: CEZ:AV0Z50390512 Keywords : neurogenic pulmonary edema * intracranial pressure * sympathetic system Subject RIV: FH - Neurology

  18. Edema and malignancy in meningiomas

    OpenAIRE

    Mattei,Tobias Alécio; Mattei,Josias Alécio; Ramina,Ricardo; Aguiar,Paulo Henrique; Plese,José Pindaro; Marino Jr,Raul

    2005-01-01

    PURPOSE: In recent years there have been many attempts to define a subset of aggressive malignant meningiomas based on histopathology and imaging technologies. The purpose of this study was to evaluate the level of peritumoral edema and its volume using the imaging technologies, computer tomography and magnetic resonance imaging, and correlate these results with the histological WHO classification. Reported causes of tumoral edema and its relationships to the histological characteristics were...

  19. Negative-Pressure Pulmonary Edema.

    Science.gov (United States)

    Bhattacharya, Mallar; Kallet, Richard H; Ware, Lorraine B; Matthay, Michael A

    2016-10-01

    Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  20. Acute Mountain Sickness: Relationship to Brain Volume and Effect of Oral Glycerol Prophylaxis

    National Research Council Canada - National Science Library

    Muza, Stephen

    1998-01-01

    ... development of cerebral edema. Furthermore, to assess whether AMS was associated with development of cerebral edema, we used MR imaging and post-processing to quantify changes in brain tissue volume, hypothesized to increase due to cerebral edema...

  1. Temporal delta wave and ischemic lesions on MRI

    International Nuclear Information System (INIS)

    Inui, Koji; Kawamoto, Hozumi; Kawakita, Masahiko; Wako, Kazuhisa; Nakashima, Hiromichi; Kamihara, Masanori; Nomura, Junichi

    1994-01-01

    The present study was designed to determine the clinical significance of a temporal low-voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain. (author)

  2. Inhibition of VEGF Signaling Reduces Diabetes-Exacerbated Brain Swelling, but Not Infarct Size, in Large Cerebral Infarction in Mice.

    Science.gov (United States)

    Kim, Eunhee; Yang, Jiwon; Park, Keun Woo; Cho, Sunghee

    2017-12-30

    In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain. Additionally, SU5416, a VEGFR2 inhibitor, was treated in the type 1/2 diabetic mice, and stroke outcomes were determined. All diabetic groups displayed bigger infarct volume and brain swelling compared to nondiabetic mice, and the increased swelling was disproportionately larger relative to infarct enlargement. Diabetic conditions significantly increased VEGF-A, Esm1, and VEGFR2 expressions in the ischemic brain compared to nondiabetic mice. Notably, in diabetic mice, VEGFR2 mRNA levels were positively correlated with brain swelling, but not with infarct volume. Treatment with SU5416 in diabetic mice significantly reduced brain swelling. The study shows that brain swelling is a predominant pathological event in diabetic stroke and that an underlying event for diabetes-enhanced brain swelling includes the activation of VEGF signaling. This study suggests consideration of stroke therapies aiming at primarily reducing brain swelling for subjects with diabetes.

  3. Migraine, the heart and the brain

    NARCIS (Netherlands)

    Koppen, H.

    2018-01-01

    The association between migraine and silent ischemic brain lesions was investigated. Also the occurence of right-to-left shunts in different migraine groups and controls. The functional consequences of silent ischemic brain lesions were investigated.

  4. Transient central diabetes insipidus following ischemic stroke

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Jayaraman

    2013-01-01

    Full Text Available Central Diabetes Insipidus (CDI following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery.

  5. A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

    Science.gov (United States)

    Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

    2014-01-01

    Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

  6. Correlation of Tumor and Peritumoral Edema Volumes with Survival in Patients with Cerebral Metastases.

    Science.gov (United States)

    Kerschbaumer, Johannes; Bauer, Marlies; Popovscaia, Marina; Grams, Astrid E; Thomé, Claudius; Freyschlag, Christian F

    2017-02-01

    Surgical resection in combination with radiotherapy in selected cases remains the best option for patients with cerebral metastases. Postoperative relapse of brain metastases occurs frequently and can be reduced by postoperative whole-brain radiotherapy (WBRT). Continuous spread of tumor cells from the primary lesions is debated as a cause of recurrence. It is well known that in gliomas, infiltration takes place within the surrounding edema. Obviously, most brain metastases are usually associated with peritumoral edema, which may act as an indicator of infiltration and more aggressive tumor biology. Therefore, we aimed to investigate the correlation of tumor and edema volumes with overall survival in patients with cerebral metastases. A total of 143 patients diagnosed with brain metastasis (male:female=1.1:1) who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient files. The volumes of tumor and edema calculated by manual delineation. The ratio of edema to tumor volume was calculated, leading to dichotomization of the patients. The median tumor volume was 20.1 cc (range=0.8-90.8 cc) and the me