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1

Potential of glyburide to reduce intracerebral edema in brain metastases.  

PubMed

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema. PMID:24552576

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

2

Hyperbaric Oxygen Reduces Blood-Brain Barrier Damage and Edema After Transient Focal Cerebral Ischemia  

Microsoft Academic Search

Background and Purpose—Hyperbaric oxygen (HBO) has been shown to protect the brain parenchyma against transient focal cerebral ischemia, but its effects on the ischemic microcirculation are largely unknown. We examined the potential of HBO to reduce postischemic blood-brain barrier (BBB) damage and edema. Methods—Wistar rats and C57\\/BL6 mice underwent occlusion of the middle cerebral artery (MCAO) for 2 hours. Forty

Roland Veltkamp; Dirk A. Siebing; Li Sun; Sabine Heiland; Katja Bieber; Hugo H. Marti; Simon Nagel; Stefan Schwab; Markus Schwaninger

2010-01-01

3

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

PubMed Central

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. PMID:22269349

2012-01-01

4

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

PubMed Central

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

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

2014-01-01

5

Pathophysiological aspects of brain edema  

Microsoft Academic Search

Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation

Igor Klatzo

1987-01-01

6

Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.  

PubMed

Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. Peripheral leukocytes can infiltrate the injured brain, thereby aggravating BBB leakage and neuroinflammation. Thus, anti-inflammatory pharmacotherapies may ameliorate EBI and provide neuroprotection after SAH. Cannabinoid type 2 receptor (CB2R) agonism has been shown to reduce neuroinflammation; however, the precise protective mechanisms remain to be elucidated. This study aimed to evaluate whether the selective CB2R agonist, JWH133 can ameliorate EBI by reducing brain-infiltrated leukocytes after SAH. Adult male Sprague-Dawley rats were randomly assigned to the following groups: sham-operated, SAH with vehicle, SAH with JWH133 (1.0mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0mg/kg). SAH was induced by endovascular perforation, and JWH133 was administered 1h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24h after surgery. JWH133 improved neurological scores and reduced brain water content; however, SR144528 reversed these treatment effects. JWH133 reduced Evans blue dye extravasation after SAH. Furthermore, JWH133 treatment significantly increased TGF-?1 expression and prevented an SAH-induced increase in E-selectin and myeloperoxidase. Lastly, SAH resulted in a decreased expression of the tight junction protein zonula occludens-1 (ZO-1); however, JWH133 treatment increased the ZO-1 expression. We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-?1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH. PMID:24819918

Fujii, Mutsumi; Sherchan, Prativa; Krafft, Paul R; Rolland, William B; Soejima, Yoshiteru; Zhang, John H

2014-07-15

7

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

PubMed

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

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

2014-01-01

8

Radiosurgery for brain metastases and cerebral edema.  

PubMed

The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9years. During the 2months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6mg/day, the mean metastasis volume decreased from 3.79±4.12cc to 2.8±4.48cc (p=0.001), and the mean edema volume decreased from 16.91±30.15cc to 12.85±24.47cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0-2cc) and increased in four patients (by >10%, 2-14cc). In a subanalysis of eight metastases with baseline edema volume greater than 40cc, edema volume decreased from 77.27±37.21cc to 24.84±35.6cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

2015-03-01

9

Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits  

PubMed Central

Background Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. Results The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5’-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH?+?saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. Conclusion The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH. PMID:22587664

2012-01-01

10

Experimental drug therapy of peritumoral brain edema  

Microsoft Academic Search

Four drugs with potential anti-peritumoral brain edema activity were studied using the VX2 rabbit brain tumor model. Meclofenamate and indomethacin were tested in an attempt to confirm recent reports of anti-edema activity in non steroidal anti-inflammatory drugs (NSAID's). The “angiostatic” steroids 17 hydroxyprogesterone and epicortisol were tested because of their lack of glucocorticoid and mineralocorticoid effects and their structural similarity

David E. Weissman; Cynithia Stewart

1988-01-01

11

Role of leukotrienes as mediator compounds in brain edema.  

PubMed

Leukotrienes accumulate in brain tissue after cerebral ischemia and in brain tumors. Thus, their release might contribute to the blood-brain barrier damage observed under these conditions and, hence, brain edema. The effect of these substances on the permeability of pial vessels and whether inhibition of LT synthesis reduces cold injury brain edema were studied. The pial vasculature of cats was studied by fluorescence microscopy. The cortex was superfused with LTC4, LTD4, or LTE4 via a cranial window. Na(+)-fluorescein was intravenously administered as blood-brain barrier indicator. LT concentrations up to 2 microM did not induce any leakage of the blood-brain barrier indicator into the parenchyma. However, all LTs tested constricted pial arteries and veins. Brain edema formation was studied in rabbits with cold injury. BW755C, an inhibitor of cyclooxygenase and lipoxygenase preventing formation of LTs, was given before and after trauma. Control animals received saline only. BW755C was ineffective in attenuating cold injury edema. Hemispheric swelling in control animals was 7.8 +/- 1.1%, and 7.7 +/- 0.4% in animals with treatment. LTs, even when administered to the brain in concentrations exceeding levels occurring under pathological conditions, did not induce barrier damage, nor did inhibition of LT synthesis attenuate formation of vasogenic edema. The results provide further evidence against LTs as mediator compounds of this process. PMID:2118715

Unterberg, A; Schmidt, W; Wahl, M; Baethmann, A

1990-01-01

12

Brain edema in diseases of different etiology.  

PubMed

Cerebral edema is a potentially life-threatening complication shared by diseases of different etiology, such as diabetic ketoacidosis, acute liver failure, high altitude exposure, dialysis disequilibrium syndrome, and salicylate intoxication. Pulmonary edema is also habitually present in these disorders, indicating that the microcirculatory disturbance causing edema is not confined to the brain. Both cerebral and pulmonary subclinical edema may be detected before it becomes clinically evident. Available evidence suggests that tissue hypoxia or intracellular acidosis is a commonality occurring in all of these disorders. Tissue ischemia induces physiological compensatory mechanisms to ensure cell oxygenation and carbon dioxide removal from tissues, including hyperventilation, elevation of red blood cell 2,3-bisphosphoglycerate content, and capillary vasodilatation. Clinical, laboratory, and necropsy findings in these diseases confirm the occurrence of low plasma carbon dioxide partial pressure, increased erythrocyte 2,3-bisphosphoglycerate concentration, and capillary vasodilatation with increased vascular permeability in all of them. Baseline tissue hypoxia or intracellular acidosis induced by the disease may further deteriorate when tissue oxygen requirement is no longer matched to oxygen delivery resulting in massive capillary vasodilatation with increased vascular permeability and plasma fluid leakage into the interstitial compartment leading to edema affecting the brain, lung, and other organs. Causative factors involved in the progression from physiological adaptation to devastating clinical edema are not well known and may include uncontrolled disease, malfunctioning adaptive responses, or unknown factors. The role of carbon monoxide and local nitric oxide production influencing tissue oxygenation is unclear. PMID:22579570

Adeva, María M; Souto, Gema; Donapetry, Cristóbal; Portals, Manuel; Rodriguez, Alberto; Lamas, David

2012-07-01

13

Reduced Brain Edema and Infarction Volume in Mice Lacking the Neuronal Isoform of Nitric Oxide Synthase After Transient MCA Occlusion  

Microsoft Academic Search

Infarct volume and edema were assessed after transient focal ischemia in mice lacking neuronal nitric oxide synthase (NOS) gene expression. With use of an 8–0 coated monofilament, the middle cerebral artery (MCA) of mutant (n = 32) and wild-type mice [SV-129 (n = 31), C57Black\\/6 (n = 18)] were occluded for 3 h and reperfused for up to 24 h.

Hideaki Hara; Paul L. Huang; Nariman Panahian; Mark C. Fishman; Michael A. Moskowitz

1996-01-01

14

Evidence against leukotrienes as mediators of brain edema.  

PubMed

Leukotrienes are powerful metabolites of arachidonic acid which are known to increase the permeability of peripheral blood vessels. These substances are found in brain tissue in association with cerebral ischemia, and in brain tumors. Therefore, it has been proposed that leukotrienes have a mediator function in brain edema. This hypothesis was subjected to further experimental analysis in this study, in which the authors investigated whether: 1) superfusion of the exposed brain surface with leukotrienes increases the permeability of extraparenchymal blood vessels in vivo; 2) intraparenchymal infusion of leukotrienes induces brain edema; and 3) pharmacological inhibition of leukotriene formation by BW755C, an inhibitor of leukotriene synthesis, reduces formation of brain edema from a standardized traumatic insult. The pial vessels of the parietal cortex of cats were examined by fluorescence microscopy during cerebral superfusion with the leukotrienes C4 (LTC4), D4 (LTD4), or E4 (LTE4) by using an open cranial window preparation. Intravenous Na(+)-fluorescein served as an in vivo blood-brain barrier (BBB) indicator. Superfusion of the pia with leukotrienes (up to 2 microM) did not open the barrier to fluorescein, but was associated with a significant constriction (up to 25%) of arterial and venous vessels. In experiments with slow infusion of leukotriene B4 (LTB4) or LTC4 into the white matter of feline brain, the tissue water content was subsequently determined in serial brain slices using the specific gravity method. Tissue water profiles obtained after a 15-microM infusion of either LTB4 or LTC4 were virtually identical with those of control animals infused with mock cerebrospinal fluid. Thus, neither LTB4 nor LTC4 led to an augmentation of infusion-induced brain edema. In a final series, a cold lesion of the left parietal cortex was induced in rabbits. Twenty-four hours later, swelling of the exposed hemisphere was quantified by gravimetrical comparison of its weight with that of the contralateral nontraumatized hemisphere. Eight animals received BW755C intravenously prior to and after trauma to inhibit formation of leukotrienes. Seven rabbits were infused with an equivalent volume of saline as a control study. The resulting hemispheric swelling was 7.7% +/- 0.6% (mean +/- standard error of the mean) 24 hours later in animals receiving BW755C and 7.8% +/- 1.2% in the control group, indicating that inhibition of leukotrienes was ineffective in preventing formation of vasogenic brain edema. The findings demonstrate that leukotrienes administered to the brain in concentrations occurring under pathological conditions do not open the BBB nor do they induce brain edema.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2013778

Unterberg, A; Schmidt, W; Wahl, M; Ellis, E F; Marmarou, A; Baethmann, A

1991-05-01

15

Aquaporin4 facilitates reabsorption of excess fluid in vasogenic brain edema  

Microsoft Academic Search

Aquaporin-4 (AQP4) is the major water channel in the brain, expressed predominantly in astroglial cell membranes. Initial studies in AQP4-deficient mice showed reduced cellular brain edema following water intoxication and ischemic stroke. We hypothesized that AQP4 deletion would have the opposite effect (increased brain swelling) in vasogenic (noncellular) edema because of impaired removal of excess brain water through glial limitans

Marios C. Papadopoulos; Geoffrey T. Manley; Sanjeev Krishna; A. S. Verkman

2004-01-01

16

Local drug delivery for treatment of brain tumor associated edema  

E-print Network

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

Ong, Qunya

2014-01-01

17

The novel antiepileptic agent RWJ-333369-A, but not its analog RWJ-333369, reduces regional cerebral edema without affecting neurobehavioral outcome or cell death following experimental traumatic brain injury  

PubMed Central

Purpose To evaluate the therapeutic efficacy of two antiepileptic compounds, RWJ-333369 and RWJ-333369-A in a well-established experimental model of lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Methods Anethestized Male Sprague-Dawley rats (n = 227) were subjected to lateral FP brain injury or sham-injury. Animals were randomized to receive treatment with RWJ-333369 (60 mg/kg, p.o.) or its analog RWJ-333369-A (60 mg/kg, p.o.), or vehicle (equal volume) at 15 minutes, 4, 8, and 24 hours post-injury. In Study I, animals were assessed at 48 hours for acute motor and cognitive function and then sacrificed to evaluate regional cerebral edema. In Study II, animals were evaluated post-injury for motor function at 48 hours and weekly thereafter from 1 to 4 weeks. Post-traumatic learning ability was assessed 4 weeks post-injury, followed by evaluation of hemispheric tissue loss. Results In Study I, no improvement in acute memory or motor function was observed following administration of either RWJ-333369 or RWJ-333369-A in brain-injured animals compared to vehicle-treated, brain-injured animals. However, brain-injured animals receiving treatment with RWJ-333369-A had a significant reduction in post-traumatic cerebral edema in both injured and contralateral hippocampus compared to brain-injured, vehicle-treated controls (p < 0.05). In Study II, treatment with either compound did not result in any improvement of neuromotor function, learning ability or change in lesion volume following brain injury. Conclusions These results indicate that the novel antiepileptic compound RWJ-333369-A reduces post-traumatic hippocampal edema without affecting neurobehavioral or histological outcome. It remains unclear whether this small effect on hippocampal edema is related to the ability of this compound to attenuate seizure activity. PMID:17726266

Keck, Carrie A.; Thompson, Hilaire J.; Pitkänen, Asla; LeBold, David G.; Morales, Diego M.; Plevy, Jamie B.; Puri, Rishi; Zhao, Boyu; Dichter, Marc; McIntosh, Tracy K.

2008-01-01

18

Proton nuclear magnetic resonance studies on brain edema  

SciTech Connect

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.

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

1982-06-01

19

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

PubMed

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

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

2014-11-01

20

Drowning stars: Reassessing the role of astrocytes in brain edema  

PubMed Central

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

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

2014-01-01

21

Treatment of Brain Edema in Acute Liver Failure  

Microsoft Academic Search

Opinion statement  Cerebral edema is very common in patients with acute liver failure and encephalopathy. In severe cases, it produces brain\\u000a tissue shift and potentially fatal herniation. Brain swelling in acute liver failure is produced by a combination of cytotoxic\\u000a (cellular) and vasogenic edema. Accumulation of ammonia and glutamine leads to disturbances in the regulation of cerebral\\u000a osmolytes, increased free radical

Alejandro A. Rabinstein

2010-01-01

22

Evaluation of brain edema using magnetic resonance proton relaxation times  

SciTech Connect

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

Fu, Y.; Tanaka, K.; Nishimura, S. (Baba Memorial Hospital, Osaka (Japan))

1990-01-01

23

Effect of Small Molecule Vasopressin V1a and V2 Receptor Antagonists on Brain Edema Formation and Secondary Brain Damage following Traumatic Brain Injury in Mice.  

PubMed

The attenuation of brain edema is a major therapeutic target after traumatic brain injury (TBI). Vasopressin (AVP) is well known to play a major role in the regulation of brain water content and vasoendothelial functions and to be involved in brain edema formation. Therefore, the aim of the current study was to analyze the antiedematous efficacy of a clinically relevant, nonpeptidic AVP V1a and V2 receptor antagonists. C57Bl6 mice were subjected to controlled cortical impact (CCI) and V1a or V2 receptors were inhibited by using the highly selective antagonists SR-49059 or SR-121463A either by systemic (intraperitoneal, IP) or intracerebroventricular (ICV) application. After 24?h, brain edema, intracranial pressure (ICP), and contusion volume were assessed. Systemically applied AVP receptor antagonists could not reduce secondary lesion growth. In contrast, ICV administration of AVP V1a receptor antagonist decreased brain edema formation by 68%, diminished post-traumatic increase of ICP by 46%, and reduced secondary contusion expansion by 43% 24?h after CCI. The ICV inhibition of V2 receptors resulted in significant reduction of post-traumatic brain edema by 41% 24?h after CCI, but failed to show further influence on ICP and lesion growth. Hence, centrally applied vasopressin V1a receptor antagonists may be used to reduce brain edema formation after TBI. PMID:25111427

Krieg, Sandro M; Sonanini, Sebastian; Plesnila, Nikolaus; Trabold, Raimund

2015-02-15

24

Edema  

MedlinePLUS

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

25

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

PubMed Central

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

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

2015-01-01

26

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

PubMed Central

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

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

2015-01-01

27

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

PubMed Central

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

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

2014-01-01

28

Serine protease inhibitor attenuates intracerebral hemorrhage-induced brain injury and edema formation in rat.  

PubMed

Our previous studies have demonstrated that thrombin plays an important role in intracerebral hemorrhage (ICH)-induced brain injury and edema formation. We, therefore, examined whether nafamostat mesilate (FUT), a serine protease inhibitor, can reduce ICH-induced brain injury. Anesthetized male Sprague-Dawley rats received an infusion of autologous whole blood (100 microL), thrombin (5U/50 microL) or type VII collagenase (0.4 U/2 microL) into the right basal ganglia, the three ICH models used in the present study. FUT (10 mg/kg) or vehicle was administered intraperitoneally 6 h after ICH (or immediately after thrombin infusion) and then at 12-h intervals (six treatments in total, n = 5 in each group). All rats were sacrificed 72 h later. We also examined whether FUT promotes rebleeding in a model in which ICH was induced by intracerebral injection of collagenase. Systemic administration of FUT starting 6 h after ICH reduced brain water content in the ipsilateral basal ganglia 72 h after ICH compared with vehicle. FUT attenuated ICH-induced changes in 8-OHdG and thrombin-reduced brain edema. FUT did not increase collagenase-induced hematoma volume. FUT attenuates ICH-induced brain edema and DNA injury suggesting that serine protease inhibitor may be potential therapeutic agent for ICH. PMID:19812969

Nakamura, Takehiro; Kuroda, Yasuhiro; Hosomi, Naohisa; Okabe, Naohiko; Kawai, Nobuyuki; Tamiya, Takashi; Xi, Guohua; Keep, Richard F; Itano, Toshifumi

2010-01-01

29

The effects of Tanshinone IIA on blood-brain barrier and brain edema after transient middle cerebral artery occlusion in rats.  

PubMed

Disruption of blood-brain barrier (BBB) and edema formation play a key role in the development of neurological dysfunction after cerebral ischemia. In this study, the effects of Tanshinone IIA (Tan IIA), one of the active ingredients of Salvia miltiorrhiza root, on the BBB and brain edema after transient middle cerebral artery occlusion in rats were examined. Our study demonstrated that Tan IIA reduced brain infarct area, water content in the ischemic hemisphere. Furthermore, Tan IIA significantly decreased BBB permeability to Evans blue, suppressed the expression of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), inhibited the degradation of tight junction proteins zonula occludens-1 (ZO-1) and Occludin. These results demonstrated that Tan IIA was effective for attenuating the extent of brain edema formation in response to ischemia injury in rats, partly by Tan IIA's protective effect on the BBB. Our results may have implications in the treatment of brain edema in cerebral ischemia. PMID:20570121

Tang, Chao; Xue, Hongli; Bai, Changlin; Fu, Rong; Wu, Anhua

2010-12-01

30

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

PubMed

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

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

2013-03-01

31

Hydrogen sulfide inhalation decreases early blood-brain barrier permeability and brain edema induced by cardiac arrest and resuscitation.  

PubMed

The effects of hydrogen sulfide (H2S) on blood-brain barrier (BBB) and brain edema after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. We investigated the effects of exogenous 80-p.p.m. H2S gas on BBB, brain water content, neurologic outcome, and survival rate after CA and CPR. Cardiopulmonary resuscitation followed CA induced in rats by ventricular fibrillation for 6?minutes. Results show that inhalation of 80-p.p.m. H2S significantly reduced the permeability of the BBB in both in the cortex and hippocampus at 24?hours after resuscitation. Hydrogen sulfide also lessened brain edema in the cortex and hippocampus, ameliorated neurologic outcome as evaluated by neurologic deficit score and tape removal test, and improved the 14-day survival rate. Hydrogen sulfide also attenuated CA and CPR-induced increases of matrix metalloproteinase-9 (MMP-9) activity and vascular endothelial growth factor (VEGF) expression, and increased the expression of angiogenin-1 (Ang-1). These results indicate that inhalation of 80-p.p.m. H2S immediately after CPR attenuated BBB permeability and brain edema, and improved neurologic outcome and 14-day survival of rats after CA. The therapeutic benefits of H2S could be associated with suppression of MMP-9 and VEGF expression and increased expression of Ang-1. PMID:25492119

Geng, Yingjie; Li, Eerdunmutu; Mu, Qier; Zhang, Yu; Wei, Xia; Li, Hangbing; Cheng, Long; Zhang, Bing

2015-03-01

32

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

PubMed

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

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

2014-02-01

33

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

PubMed

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

Laird, Melissa D; Sukumari-Ramesh, Sangeetha; Swift, Andrew E B; Meiler, Steffen E; Vender, John R; Dhandapani, Krishnan M

2010-05-01

34

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

PubMed Central

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

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

2010-01-01

35

The Effects of Selective Brain Hypothermia and Decompressive Craniectomy on Brain Edema After Closed Head Injury in Mice  

Microsoft Academic Search

\\u000a Intractable brain edema remains one of the main causes of death after traumatic brain injury (TBI). Brain hypothermia and\\u000a decompressive craniectomy have been considered as potential therapies. The goal of our experimental study was to determine\\u000a if selective hypothermia in combination with craniectomy could modify the development of posttraumatic brain edema. Male CD-1\\u000a mice were anesthetized with halothane and randomly

Jacek Szczygielski; Angelika E. Mautes; Karsten Schwerdtfeger; Wolf-Ingo Steudel

36

Effect of delayed albumin hemodilution on infarction volume and brain edema after transient middle cerebral artery occlusion in rats.  

PubMed

The authors examined the effect of delayed high-concentration albumin therapy on ischemic injury in a highly reproducible model of middle cerebral artery (MCA) occlusion in rats. Male Sprague-Dawley rats weighing 270 to 320 g were anesthetized with halothane and subjected to 120 minutes of temporary MCA occlusion induced by means of a poly-L-lysine-coated intraluminal nylon suture inserted retrograde via the external carotid artery into the internal carotid artery and MCA. The agent (20% human serum albumin [HSA]) or control solution (sodium chloride 0.9%) was administered intravenously at a dosage of 1% of body weight immediately after suture removal following a 2-hour period of MCA occlusion. The animals' neurological status was evaluated during MCA occlusion (at 60 minutes) and daily for 3 days thereafter. The brains were perfusion-fixed, and infarct volumes and brain edema were determined. The HSA significantly improved the neurological score compared with saline at 24 hours after MCA occlusion. The rats treated with HSA also had significantly reduced total infarct volume (by 34%) and brain edema (by 81%) compared with saline-treated rats. There was a strong correlation between hematocrit level and brain edema (p < 0.01), and between total infarct volume or brain edema and neurological score at 24, 48, and 72 hours postinjury (p < 0.0002). These results strongly support the beneficial effect of delayed albumin therapy in transient focal ischemia and indicate its possible usefulness in treating patients with acute ischemic stroke. PMID:9322848

Belayev, L; Busto, R; Zhao, W; Clemens, J A; Ginsberg, M D

1997-10-01

37

PERFUSIONAL DEFICIT AND THE DYNAMICS OF CEREBRAL EDEMAS IN EXPERIMENTAL TRAUMATIC BRAIN INJURY USING PERFUSION AND  

E-print Network

PERFUSIONAL DEFICIT AND THE DYNAMICS OF CEREBRAL EDEMAS IN EXPERIMENTAL TRAUMATIC BRAIN INJURY was observed, demonstrated by an increase in apparent diffusion coefficient. Keywords: Traumatic brain injury percussion. inserm-00344238,version1-4Dec2008 #12;Introduction Traumatic brain injury (TBI) is a worldwide

Paris-Sud XI, Université de

38

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

NASA Astrophysics Data System (ADS)

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

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

2011-01-01

39

Expression of Aquaporin 4 and Breakdown of the Blood-Brain Barrier after Hypoglycemia-Induced Brain Edema in Rats  

PubMed Central

Background Hypoglycemia-induced brain edema is a severe clinical event that often results in death. The mechanisms by which hypoglycemia induces brain edema are unclear. Methods In a hypoglycemic injury model established in adult rats, brain edema was verified by measuring brain water content and visualizing water accumulation using hematoxylin and eosin staining. Temporal expression of aquaporin 4 (AQP4) and the integrity of the blood-brain barrier (BBB) were evaluated. We assessed the distribution and expression of AQP4 following glucose deprivation in astrocyte cultures. Results Brain edema was induced immediately after severe hypoglycemia but continued to progress even after recovery from hypoglycemia. Upregulation of AQP4 expression and moderate breakdown of the BBB were observed 24 h after recovery. In vitro, significant redistribution of AQP4 to the plasma membrane was induced following 6 h glucose deprivation. Conclusion Hypoglycemia-induced brain edema is caused by cytotoxic and vasogenic factors. Changes in AQP4 location and expression may play a protective role in edema resolution. PMID:25264602

Deng, Jiangshan; Zhao, Fei; Yu, Xiaoyan; Zhao, Yuwu; Li, Dawei; Shi, Hong; Sun, Yongning

2014-01-01

40

Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice  

PubMed Central

Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer's (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27?mm?Hg for 35?minutes. Mice (n=10/group) were then resuscitated with a 20?mL/kg bolus of 4% PNPH or LR followed by 10?mL/kg boluses targeting MAP>70?mm?Hg for 90?minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7?mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83?mm?Hg, P<0.001). The PNPH-treated mice required only 20?mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12?mm?Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68?mm?Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development. PMID:23801241

Brockman, Erik C; Bay?r, Hülya; Blasiole, Brian; Shein, Steven L; Fink, Ericka L; Dixon, CEdward; Clark, Robert SB; Vagni, Vincent A; Ma, Li; Hsia, Carleton JC; Tisherman, Samuel A; Kochanek, Patrick M

2013-01-01

41

[Effect of phenothiazine derivatives on the development of experimental traumatic brain edema].  

PubMed

The effect of levomepromazin, propazin, diprazin and dyphenhydramine on the development of traumatic edema of the brain has been studied. Phenothiazine derivatives with an unbranched dialkylaminoalkyl side chain at the nitrogen atom (propazin) have been found to produce the most remarkable antiedematic action. The drugs that have a branched dialkylaminoalkyl chain (levomepromazin, diprazin) do not return brain water content to normal. PMID:7140953

Platonov, I A; Iasnetsov, V S

1982-01-01

42

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

Microsoft Academic Search

Vasogenic brain edema was induced in cats by cold injury (six animals), brain tumors (five animals), and brain abscesses (six animals). Water and electrolyte content, specific gravity, blood volume, and the amount of extravasated serum proteins were determined in small tissue samples taken from gray and white matter at various distances from the lesion. Edema was strictly confined to the

H.-W. Bothe; W. Bodsch; K.-A. Hossmann

1984-01-01

43

Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice  

PubMed Central

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 1? 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 inflammation without major differences in morphological brain damage compared to young. PMID:22952778

Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

2012-01-01

44

Acupuncture and moxibustion reduces neuronal edema in Alzheimer's disease rats  

PubMed Central

To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer's disease, we established a rat model of Alzheimer's disease and measured axin and ?-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacupuncture, or both, at Baihui (GV20) and Shenshu (BL23). Axin expression was lower, ?-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuroprotective effect of acupuncture and moxibustion in Alzheimer's disease is associated with axin and ?-catenin expression in the Wnt signal transduction pathway. PMID:25206919

Zhou, Hua; Sun, Guojie; Kong, Lihong; Du, Yanjun; Shen, Feng; Wang, Shuju; Chen, Bangguo; Zeng, Xiaoling

2014-01-01

45

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

PubMed

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

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

2015-04-01

46

Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study.  

PubMed

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection. PMID:25792869

Song, Juhyun; Park, Joohyun; Kim, Jae Hwan; Choi, Ja Yong; Kim, Jae Young; Lee, Kyoung Min; Lee, Jong Eun

2015-03-01

47

Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study  

PubMed Central

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.

Song, Juhyun; Park, Joohyun; Kim, Jae Hwan; Choi, Ja Yong; Kim, Jae Young; Lee, Kyoung Min

2015-01-01

48

Nicotine Exacerbates Brain Edema during In Vitro and In Vivo Focal Ischemic Conditions  

PubMed Central

We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na+,K+,2Cl? cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation. PMID:19889792

Paulson, Jennifer R.; Yang, Tianzhi; Selvaraj, Pradeep K.; Mdzinarishvili, Alexander; Van der Schyf, Cornelis J.; Klein, Jochen; Bickel, Ulrich

2010-01-01

49

Candesartan Attenuates Ischemic Brain Edema and Protects the Blood–Brain Barrier Integrity from Ischemia/Reperfusion Injury in Rats  

PubMed Central

Background: Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat. Methods: Rats were exposed to 60-min middle cerebral artery (MCA) occlusion. Vehicle and non-hypotensive doses of candesartan (0.1 mg/kg) were administered one hour before ischemia. Neurological dysfunction scoring was evaluated following 24 h of reperfusion. Animals were then decapitated under deep anesthesia for the assessments of cerebral infarct size, edema formation, and BBB permeability. Results: The outcomes of 24 h reperfusion after 60-min MCA occlusion were severe neurological disability, massive BBB disruption (Evans blue extravasation = 12.5 ± 1.94 µg/g tissue), 4.02% edema, and cerebral infarction (317 ± 21 mm3). Candesartan at a dose of 0.1 mg/kg, without changing arterial blood pressure, improved neurological dysfunction scoring together with significant reductions in BBB disruption (54.9%), edema (59.2%), and cerebral infarction (54.9%). Conclusions: Inactivation of central AT1 receptors, if not accompanied with arterial hypotension, protected cerebral micro-vasculatures from damaging effects of acute stroke. PMID:25326022

Panahpour, Hamdollah; Nekooeian, Ali Akbar; Dehghani, Gholam Abbas

2014-01-01

50

Proton nuclear magnetic resonance studies on brain edema  

Microsoft Academic Search

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

Shoji Naruse; Yoshiharu Horikawa; Chuzo Tanaka; Kimiyoshi Hirakawa; Hiroyasu Nishikawa; Kazuo Yoshizaki

1982-01-01

51

Effects of focal mild hypothermia on thrombin-induced brain edema formation and the expression of protease activated receptor-1, matrix metalloproteinase-9 and aquaporin 4 in rats.  

PubMed

Hypothermia is an effective neuroprotective treatment for brain injury caused by intracerebral hemorrhage (ICH). It is reported to reduce brain edema and neuronal cell death. Thrombin, a coagulation protease released from blood clots, is critical in brain edema formation following ICH. Protease activated receptor?1 (PAR?1), matrix metalloproteinase?9 (MMP?9) and aquaporin 4 (AQP4) are edema?associated mediators that have been implicated in ICH pathology. In the present study, thrombin was used to induce brain edema in adult male Sprague?Dawley rats. Differences between a focal mild hypothermic group (33±0.5?C) and a normothermic group (37?C) were investigated. Following hypothermia, brain water content and blood?brain barrier (BBB) disruption was assessed at 6, 24 and 48 h and subsequently at 3, 5 and 7 days. At the same time, the mRNA and protein expression of PAR?1, MMP?9 and AQP4 were also determined. It was identified that brain water content and BBB disruption increased at 6 h and reached a maximal level at 24 h in the normothermic group. The mRNA and protein expression levels of PAR?1, MMP?9 and AQP4 started to increase at 24 h and reached a maximal level at 48 h. Focal mild hypothermia tended to significantly reduce brain water content, BBB disruption and PAR?1, MMP?9 and AQP expression at 24 and 48 h. The present data suggest that focal mild hypothermia is an effective treatment for edema formation through moderation of the mRNA and protein expression of PAR?1, MMP?9 and AQP4. PMID:25523640

Gao, Dapeng; Ding, Feifan; Lei, Gongwen; Luan, Guohui; Zhang, Shibao; Li, Kesen; Wang, Desheng; Zhang, Liming; Dai, Dawei

2015-04-01

52

Activation of P2X7 Promotes Cerebral Edema and Neurological Injury after Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7?/? mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1? (IL-1?) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1? expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation. PMID:22815977

Kimbler, Donald E.; Shields, Jessica; Yanasak, Nathan; Vender, John R.; Dhandapani, Krishnan M.

2012-01-01

53

SEGMENTATION OF TUMOR AND EDEMA ALONG WITH HEALTHY TISSUES OF BRAIN USING WAVELETS AND NEURAL NETWORKS.  

PubMed

Robust brain magnetic resonance (MR) segmentation algorithms are critical to analyze tissues and diagnose tumor and edema in a quantitative way. In this study, we present a new tissue segmentation algorithm that segments brain MR images into tumor, edema, white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). The detection of the healthy tissues is performed simultaneously with the diseased tissues because examining the change caused by the spread of tumor and edema on healthy tissues is very important for treatment planning. We used T1, T2 and FLAIR MR images of 20 subjects suffering from glial tumor. We developed an algorithm for stripping the skull before the segmentation process. The segmentation is performed using self-organizing map (SOM) that is trained with unsupervised learning algorithm and fine-tuned with learning vector quantization (LVQ). Unlike other studies, we developed an algorithm for clustering the SOM instead of using an additional network. Input feature vector is constructed with the features obtained from stationary wavelet transform (SWT) coefficients. The results showed that average Dice similarity indexes are 91% for WM, 87% for GM, 96% for CSF, 61% for tumor, and 77% for edema. PMID:25265636

Demirhan, Ayse; Toru, Mustafa; Guler, Inan

2014-09-26

54

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

PubMed Central

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

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

2013-01-01

55

Feasibility of using diffuse reflectance spectroscopy for the quantification of brain edema  

NASA Astrophysics Data System (ADS)

Many diseased states of the brain can result in the displacement of brain tissues and restrict cerebral blood flow, disrupting function in a life-threatening manner. Clinical examples where displacements are observed include venous thromboses, hematomas, strokes, tumors, abscesses, and, particularly, brain edema. For the latter, the brain tissue swells, displacing the cerebral spinal fluid (CSF) layer that surrounds it, eventually pressing itself against the skull. Under such conditions, catheters are often inserted into the brain's ventricles or the subarachnoid space to monitor increased pressure. These are invasive procedures that incur increased risk of infection and consequently are used reluctantly by clinicians. Recent studies in the field of biomedical optics have suggested that the presence or absence of the CSF layer can lead to dramatic changes in NIR signals obtained from diffuse reflectance measurements around the head. In this study, we consider how this sensitivity of NIR signals to CSF might be exploited to non-invasively monitor the onset and resolution of brain edema.

Rodriguez, Juan G.; Sisson, Cynthia; Hendricks, Chad; Pattillo, Chris; McWaters, Megan; Hardjasudarma, Mardjohan; Quarles, Chad; Yaroslavsky, Anna N.; Yaroslavsky, Ilya V.; Battarbee, Harold

2001-05-01

56

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

PubMed Central

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

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

2013-01-01

57

The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury.  

PubMed

Large-conductance, calcium-activated potassium (maxi-K) channels regulate neurotransmitter release and neuronal excitability, and openers of these channels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcome after lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized Sprague-Dawley rats (n = 142) were subjected to moderate FP brain injury (n = 88) or surgery without injury (n = 54) and were randomized to receive a bolus of 0.1 mg/kg BMS-204352 (n = 26, injured; n = 18, sham), 0.03 mg/kg BMS-204352 (n = 25, injured; n = 18, sham), or 2% dimethyl sulfoxide (DMSO) in polyethylene glycol (vehicle, n = 27, injured; n = 18, sham) at 10 minutes postinjury. One group of rats was tested for memory retention (Morris water maze) at 42 hours postinjury, then killed for evaluation of regional cerebral edema. A second group of injured/sham rats was assessed for neurologic motor function from 48 hours to 2 weeks postinjury and cortical lesion area. Administration of 0.1 mg/kg BMS-204352 improved neurologic motor function at 1 and 2 weeks postinjury (P < 0.05) and reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus, and adjacent cortex (P < 0.05). Administration of 0.03 mg/kg BMS-204352 significantly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No effects on cognitive function or cortical tissue loss were observed with either dose. These results suggest that the novel maxi-K channel opener BMS-204352 may be selectively beneficial in the treatment of experimental TBI. PMID:11323525

Cheney, J A; Weisser, J D; Bareyre, F M; Laurer, H L; Saatman, K E; Raghupathi, R; Gribkoff, V; Starrett, J E; McIntosh, T K

2001-04-01

58

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

Microsoft Academic Search

The aim of the present work is to develop a non-destructive, non-invasive technique for the early diagnosis of an oncoming brain edema based on the variation of vibration characteristics of the head system (i.e. eigenfrequency spectrum and modal damping). Besides the theoretical model that supports the basic principle, the proposed technique has been verified experimentally in animal tests. The advantage

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

2006-01-01

59

Experimental Study Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats  

Microsoft Academic Search

Summary Background. Volatile anesthetics reduce neuronal excitation and ce- rebral metabolism but can also increase intracellular water accumula- tion in normal and injured brains. While attenuation of neuronal excitation and glutamate release are beneficial under pathological con- ditions, any increase in edema formation should be avoided. In the present study we investigated duration-dependent effects of the com- monly used isoflurane=nitrous

J. F. Stover; O. W. Sakowitz; S. N. Kroppenstedt; U. W. Thomale; O. S. Kempski; G. Flugge; A. W. Unterberg

60

Multi-fractal texture features for brain tumor and edema segmentation  

NASA Astrophysics Data System (ADS)

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

Reza, S.; Iftekharuddin, K. M.

2014-03-01

61

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

PubMed Central

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

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

2014-01-01

62

Therapeutical efficacy of a novel chloride transport blocker and an IP3-analogue in vasogenic brain edema.  

PubMed

The efficacy of torasemide, a novel chloride-channel blocker, and of PP56, an IP3 analogue, was currently examined in experimental brain edema. Following trephination in anesthesia rats were subjected to a focal cold injury of the left cerebral hemisphere. Animals of 4 experimental groups receiving either torasemide (i.v. at 30 min before and 6 h after lesion) or PP56 (continuous infusion beginning at 30 min before until 24 h after lesion) at two dose levels were compared with controls administered with i.v. saline. 24 h after trauma the brain was removed from the skull, and the hemispheres were separated in the median plane for gravimetric assessment of hemispheric swelling. Hct, blood gases and body temperature remained constant in all groups. Blood pressure was found to increase in a dose-dependent manner in animals with torasemide. No significant reduction of brain swelling was found in animals with low-dose torasemide (8.51 +/- 0.63%) or low- (7.91 +/- 0.60) and high-dose PP56 (6.85 +/- 1.05%) as compared to the untreated controls. Brain swelling, however, was significantly attenuated by high-dose torasemide to 7.04 +/- 0.36%, as compared to 8.89 +/- 0.29% of the untreated group (p < 0.005). It is currently studied whether torasemide reduces brain swelling when given after the insult. PMID:7976641

Berger, S; Staub, F; Stoffel, M; Eriskat, J; Schürer, L; Baethmann, A

1994-01-01

63

Topical mannitol reduces inflammatory edema in a rat model of arthritis.  

PubMed

The hexahydric alcohol mannitol is widely used to shift fluids from the intracellular to the extracellular compartments, to increase diuresis and improve mucus clearance in the airways. In principle, because of its physicochemical properties, topical mannitol might also draw fluids out of epidermis or mucosa. Here, we report that topical mannitol applications on the hind paws of rats with adjuvant-induced arthritis reduced paw thickness and tissue edema without affecting the inflammatory infiltrates. Of note, the anti-edema effects of acute (4 h) mannitol application occurred earlier than those prompted by a similar treatment with classic anti-inflammatory drugs such as diclofenac or ketoprofen. Yet, the extent of edema reduction was higher with diclofenac or ketoprofen than with mannitol when the drugs were applied in a chronic (16 h) paradigm. Together, data demonstrate that topical application of mannitol exerts potent and fast anti-edema effects in a rat model of joint inflammation, suggesting a possible utilization in patients affected by osseo-arthritic disorders. PMID:22236612

Cavone, L; Calosi, L; Cinci, L; Moroni, F; Chiarugi, A

2012-01-01

64

The Minimum Percentage of Triolein Emulsion for Studying Cerebral Vascular Permeability with Least Brain Edema  

PubMed Central

Background: Triolein emulsion infusion into the brain produces transiently increased vascular permeability. Objectives: The purpose of this study was to find the minimum percentage of triolein emulsion required for studying vascular permeability with minimal brain edema. Materials and Methods: Sixty healthy cats were divided into six groups according to the concentration of emulsified triolein infused into the carotid artery: group 1, 0.125% (n = 10); group 2, 0.25% (n = 10); group 3, 0.5% (n = 10); group 4, 1% (n = 10); group 5, 2% (n = 10); and group 6, saline infusion (control group, n = 10). T2-, T1- and contrast enhanced T1-weighted MR images were obtained 2 hours after infusing triolein emulsion. Contrast enhancement ratios (CERs) and signal intensity ratios (SIRs) versus contralateral hemispheres were calculated. Statistical analysis was performed by analysis of variance followed by Tukey’s test. P values of ? 0.05 were considered significant. Results: The lesion hemispheres showed mild hyperintensity due to edema on T2-weighted images, and contrast enhancement on post-contrast T1-weighted images in cats of group 1-5. CERs showed statistically significant differences between the control group and group 3 (P = 0.006), group 4 (P = 0.003), and group 5 (P < 0.001). However, SIRs were significantly different between the control group and group 5 only (P < 0.001). Conclusion: The minimum concentration of triolein emulsion required to increase vascular permeability adequately with minimal brain edema in a cat model was 0.5%. PMID:25780547

Choi, Seon Hee; Kim, Hak Jin; Hwangbo, Lee; Kim, Yong-Woo

2014-01-01

65

Effects of fluosol-DA on brain edema, energy metabolites, and tissue oxygen content in acute cerebral ischemia.  

PubMed

Perfluorochemicals were developed as a blood substitute and were reported to have an advantage in oxygen transport compared with blood. The present study was undertaken to investigate the therapeutic effects of a perfluorochemical, FDA, on brain edema and metabolites in acute cerebral ischemia. Cerebral ischemia was induced in SHR by BLCO followed by recirculation. The FDA administration resulted in (a) the significant inhibition of brain edema as shown by brain water content in the treated group, and (b) significant amelioration of metabolic impairments as shown by lesser degree of ATP and pyruvate decrease and lactate accumulation. The TpO2 was compared between FDA-infused and nontreated group during ischemia. The FDA-infused group had significantly higher TpO2 than nontreated group. These results indicate that the improvement of brain edema and metabolite levels were due to alleviation of ischemic hypoxia by FDA under the same ischemic insult. PMID:2118712

Memezawa, H; Katayama, Y; Shimizu, J; Suzuki, S; Kashiwagi, F; Kamiya, T; Terashi, A

1990-01-01

66

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

PubMed

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

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

2006-01-01

67

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

PubMed

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

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

2013-11-01

68

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

PubMed Central

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

Criscuolo, G. R.

1993-01-01

69

Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema  

PubMed Central

Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas. PMID:25821815

Rutkowski, Robert; Turek, Grzegorz; Mariak, Zenon; Chyczewski, Lech

2015-01-01

70

Attenuation of brain edema and spatial learning de?cits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats.  

PubMed

Diffuse brain injury (DBI) is a leading cause of mortality and disability among young individuals and adults worldwide. In specific cases, DBI is associated with permanent spatial learning dysfunction and motor deficits due to primary and secondary brain damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a major complex that produces reactive oxygen species (ROS) during the ischemic period. The complex aggravates brain damage and cell death following ischemia/reperfusion injury; however, its role in DBI remains unclear. The present study aimed to investigate the hypothesis that levels of NOX2 (a catalytic subunit of NOX) protein expression and the activation of NOX are enhanced following DBI induction in rats and are involved in aggravating secondary brain damage. A rat model of DBI was created using a modified weight-drop device. Our results demonstrated that NOX2 protein expression and NOX activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h following DBI induction. Treatment with apocynin (50 mg/kg body weight), a specific inhibitor of NOX, injected intraperitoneally 30 min prior to DBI significantly attenuated NOX2 protein expression and NOX activation. Moreover, treatment with apocynin reduced brain edema and improved spatial learning function assessed using the Morris water maze. These results reveal that treatment with apocynin may provide a new neuroprotective therapeutic strategy against DBI by diminishing the upregulation of NOX2 protein and NOX activity. PMID:23128834

Song, Si-Xin; Gao, Jun-Ling; Wang, Kai-Jie; Li, Ran; Tian, Yan-Xia; Wei, Jian-Qiang; Cui, Jian-Zhong

2013-01-01

71

Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model.  

PubMed

Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate. In the present study, we tested the hypothesis that JWH133, a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits in a clostridial collagenase VII induced GMH model in seven-day-old (P7) S-D rat pups. Up to 1h post-injury, the administration of JWH133 (1mg/kg, intraperitoneal injection) significantly attenuated brain edema at 24h post-GMH, which was reversed by a selective CB2R antagonist, SR144528 (3mg/kg, intraperitoneal injection). Long-term brain morphology and neurofunctional outcomes were also improved. In contrast, JWH133 did not have a noticeable effect on the hematoma volume during the acute phase. These data also showed that microglia activation and inflammatory cytokine (TNF-?) release were significantly inhibited by JWH133 after GMH. This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH. PMID:25625355

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

2015-03-30

72

[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema].  

PubMed

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2465014

Mabe, H; Suzuka, T; Nagai, H; Nagai, H; Koda, A

1988-07-01

73

Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism  

Microsoft Academic Search

Adult rats intubated with a single dose of ethanol (alcohol;Ç5 g\\/kg) for 5 to 10 successive days incur neurodegeneration in the entorhinal cor- tex, dentate gyrus, and olfactory bulbs accompanied by cerebrocortical edema and electrolyte (Na\\/ ,K \\/ ) accumulation. The brain damage is not lessened by cotreatment with the NMDA receptor antagonist MK- 801; also, as reported elsewhere, MK-801

MICHAEL A. COLLINS; JIAN-YUN ZOU; EDWARD J. NEAFSEY

74

Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125 I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats  

Microsoft Academic Search

Summary Background. Volatile anesthetics reduce neuronal excitation and cerebral metabolism but can also increase intracellular water accumulation in normal and injured brains. While attenuation of neuronal excitation and glutamate release are beneficial under pathological conditions, any increase in edema formation should be avoided. In the present study we investigated duration-dependent effects of the commonly used isoflurane\\/nitrous oxide (N 2O) anesthesia

J. F. Stover; O. W. Sakowitz; S. N. Kroppenstedt; U. W. Thomale; O. S. Kempski; G. Flügge; A. W. Unterberg

2004-01-01

75

Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.  

PubMed

The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events. PMID:25770058

Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

2015-05-22

76

Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study  

Microsoft Academic Search

Introduction Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary\\u000a edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was\\u000a to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients\\u000a with pulmonary edema.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This was a cross-sectional

Kosaku Komiya; Hiroshi Ishii; Shinji Teramoto; Osamu Takahashi; Nobuoki Eshima; Ou Yamaguchi; Noriyuki Ebi; Junji Murakami; Hidehiko Yamamoto; Jun-ichi Kadota

2011-01-01

77

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

SciTech Connect

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

Fike, J.R.; Seilhan, T.M.; Gobbel, G.T. (Univ. of California, San Francisco, CA (United States)); Marton, L.J. (Univ. of Wisconsin, Madison, WI (United States))

1994-04-01

78

PGJ2 Provides Prolonged CNS Stroke Protection by Reducing White Matter Edema  

PubMed Central

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

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

2012-01-01

79

Photobiostimulation reduces edema formation induced in mice by Lys-49 phospholipases A2 isolated from Bothrops moojeni venom.  

PubMed

The prominent local myotoxic effects induced by Bothrops snake venom are due, in part, to myotoxins. This effect is not neutralized by antivenom, which is the main therapy for victims of snakebite. Two basic myotoxins named MjTX-I and MjTX-II were isolated from Bothrops moojeni venom. Both myotoxins have a Lys-49 phospholipase A2 structure devoid of enzymatic activity, but are highly myonecrotic and edema-inducing. In this study, we analyzed the effect of a low-level laser (LLL) at 685 nm, an energy density of 2.2 J cm(-2), and the irradiation time of 15 s, and a light emitting diode (LED) at 635 or 945 nm at energy densities of 4 and 3.8 J cm(-2), and irradiation times of 41 and 38 s, respectively, applied 30 min and 3 h after edema formation in mice caused by MjTX-I or MjTX-II. MjTX-I or MjTX-II caused a significant edema formation in envenomed paws. LLL and LED irradiation significantly reduced the edema formation by both myotoxins from 1 up to 6 hours after the injection. Both LLL and LEDs were similar in reducing the edema formation induced by myotoxins. The combined photobiostimulation with antivenom had the same effect in reducing edema as treatment with the LLL or LEDs alone. In conclusion, the results of this study indicate that photobiostimulation could be used in association with antivenom therapy for treatment of local effects of Bothrops species venom. PMID:25232894

Nadur-Andrade, Nikele; Dale, Camila Squarzone; Santos, Adriano Silvio Dos; Soares, Andreimar M; de Lima, Carlos J; Zamuner, Stella Regina

2014-11-01

80

Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.  

PubMed

Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI. PMID:24682753

Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

2014-05-01

81

Inhaled nitric oxide for the brain dead donor with neurogenic pulmonary edema during anesthesia for organ donation: a case report  

PubMed Central

Neurogenic pulmonary edema (NPE) in brain dead organ donors occurring after an acute central nervous system insult threatens organ preservation of potential organ donors and the outcome of organ donation. Hence the active and immediate management of NPE is critical. In this case, a 50-year-old male was admitted to the intensive care unit (ICU) for organ donation. He was hypoxic due to NPE induced by spontaneous intracerebral hemorrhage and intraventricular hemorrhage. Protective ventilatory management, intermittent recruitment maneuvers, and supportive treatment were maintained in the ICU and the operating room (OR). Despite this management, the hypoxemia worsened after the OR admission. So inhaled nitric oxide (NO) therapy was performed during the operation, and the hypoxic phenomena showed remarkable improvement. The organ retrieval was successfully completed. Therefore, NO inhalation can be helpful in the improvement of hypoxemia caused by NPE in brain dead organ donors during anesthesia for the organ donation. PMID:25237451

Park, Eun Sun; Lee, A-Ran; Lee, Sang Hyun; Kim, An Suk; Park, Soon Eun; Cho, Young Woo

2014-01-01

82

Patient's Self-recognition of Reduced Visual Acuity Due to Recurrence of Macular Edema and Prompt Visitation to the Hospital in Retinal Vein Occlusion  

PubMed Central

Purpose To evaluate patients' self-recognition of reduced visual acuity due to recurring macular edema in retinal vein occlusion. Methods A retrospective review of medical records of patients who were diagnosed with recurring macular edema secondary to retinal vein occlusion was performed. The proportion of patients who recognized reduced visual acuity due to the recurrence of macular edema and who visited the hospital before the scheduled follow-up date was determined. Parameters including age, sex, diagnosis, visual acuity before recurrence of macular edema, and extent of visual acuity reduction due to recurrence of macular edema were compared in patients who recognized a reduction in visual acuity and those who did not. The proportion of patients who visited the hospital promptly was also determined. Results Forty eyes of 40 patients were included in the analysis. Sixteen and 24 patients were diagnosed with central retinal vein occlusion and branch retinal vein occlusion, respectively. Twenty-one patients (52.5%) recognized reduced visual acuity due to recurring macular edema. These patients were younger (59.2 ± 7.6 vs. 64.8 ± 9.4 years, p = 0.046), had better visual acuity before recurrence of macular edema (0.52 ± 0.48 vs. 1.02 ± 0.46, p = 0.002), and exhibited a greater reduction in visual acuity after recurrence of macular edema (0.34 ± 0.24 vs. 0.14 ± 0.13, p = 0.003). Only four patients visited the hospital before the scheduled follow-up date, and all of these patients lived relatively close to the hospital. Conclusions For prompt treatment of recurring macular edema, more intensive education about the self-estimation of visual acuity is necessary, particularly for elderly patients who have relatively poor visual acuity. In addition, a simple and easy way to identify the recurrence of macular edema at the local clinic should be established for patients who live relatively far from the hospital. PMID:24882954

Jeong, Seong Hun; Kim, Jong Woo; Lee, Tae Gon; Kim, Chul Gu; Yoo, Su Jin; Choi, Mun Jung

2014-01-01

83

The acute-phase protein PTX3 is an essential mediator of glial scar formation and resolution of brain edema after ischemic injury  

PubMed Central

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood–brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders. PMID:24346689

Rodriguez-Grande, Beatriz; Swana, Matimba; Nguyen, Loan; Englezou, Pavlos; Maysami, Samaneh; Allan, Stuart M; Rothwell, Nancy J; Garlanda, Cecilia; Denes, Adam; Pinteaux, Emmanuel

2014-01-01

84

[A trial of surgical management of brain edema in cerebral infarction--a review with our own experiences in 31 cases (author's transl)].  

PubMed

We have analyzed the clinical course of 31 cases with cerebral infarction for 4 years. Of the 31 patients, 6 cases (19%) showed the brain edema on the cerebral angiograms as manifested by the shift of the midline arteries. The patients were divided into two groups, normotensive (15 cases) and hypertensive cerebral infarction (16 cases). The clinical and angiographic findings in the normotensive groups have been differed significantly from those of the hypertensive groups. The findings of brain edema on the angiograms were prominent in the hypertensive groups, and the clinical course was generally good and fair in the normotensive groups. We have reviewed the literatures about brain edema associated with cerebral infarction and have discussed on the mechanisms. From the study of our cases, it was concluded that systemic hypertension could be a facilitatory factor in the occurrence of brain edema in cerebral infarction. Furthermore, the management of massive cerebral infarction should be reduction of increased intracranial pressure and prevention of cerebral herniation. So, it will be necessary to perform a surgical treatment such as internal decompression; removal of the infarcted, necrotized area and excision of herniated tissue, and external decompression; removal of boneflap. PMID:944869

Kakita, K; Miyazaki, T; Kadowaki, H; Izawa, M; Kubota, S

1976-03-01

85

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

PubMed Central

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

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

2010-01-01

86

Pulmonary edema  

MedlinePLUS

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

87

Vulvar edema.  

PubMed

Vulvar edema is associated with a variety of conditions. The edema can result from inflammatory conditions, infections, infestations, trauma, pregnancy, tumors and iatrogenic causes. At times, it is difficult to determine the cause of the vulvar edema. Treatment consists of determining the origin of the edema and giving the appropriate therapy for that diagnosis as well as the use of compression and, at times, lymphatic massage. PMID:20883919

Amankwah, Yaa; Haefner, Hope

2010-10-01

88

Stromal Edema in Klf4 Conditional Null Mouse Cornea is Associated with Altered Collagen Fibril Organization and Reduced Proteoglycans  

PubMed Central

Purpose Klf4, one of the highly expressed transcription factors in mouse cornea, plays an important role in maturation and maintenance of the ocular surface. Here, the authors examined the structure and proteoglycan composition of the Klf4 conditional null (Klf4CN) corneal stroma, to further characterize the previously reported Klf4CN stromal edema. Methods Collagen fibril spacing and diameter were calculated from scattering intensity profiles from small angle synchrotron X-ray scattering patterns obtained across the cornea along a vertical meridian at 0.5mm intervals. Collagen fibril organization and proteoglycans were visualised by electron microscopy (EM) with or without the cationic dye Cuprolinic blue. Proteoglycans and glycosaminoglycans were further analyzed by fluorophore-assisted carbohydrate electrophoresis (FACE) and immunoblots. Q-RT-PCR was used to measure the transcript levels. Results In the central cornea the average collagen interfibrillar Bragg spacing increased from 44.5nm (SD +/-1.8nm) in wild type to 66.5nm (SD +/-2.3nm) in Klf4CN, as measured by X-ray scattering and confirmed by EM. Mean collagen fibril diameter increased from 32nm (SD+/-0.4nm) in wild type to 42.3nm (SD+/-4.8nm) in Klf4CN corneal stroma. Downregulation of proteoglycans detected by EM in the Klf4CN stroma was confirmed by FACE and immunoblots. Q-RT-PCR showed that while the Klf4CN corneal proteoglycan transcript levels remained unchanged, matrix metalloproteinase (MMP) transcript levels were significantly upregulated. Conclusions The Klf4CN corneal stromal edema is characterized by increased collagen interfibrillar spacing and increased diameter of individual fibrils. The stroma also exhibits reduced interfibrillar proteoglycans throughout the corneal stroma, which is possibly caused by increased expression of MMPs. PMID:19387067

Young, Robert D.; Swamynathan, Shivalingappa K.; Boote, Craig; Mann, Mary; Quantock, Andrew J.; Piatigorsky, Joram; Funderburgh, James L.; Meek, Keith M.

2009-01-01

89

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

PubMed

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

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

2014-08-01

90

Diabetic macular edema.  

PubMed

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

Stefánsson, Einar

2009-07-01

91

Cysteamine alleviates early brain injury via reducing oxidative stress and apoptosis in a rat experimental subarachnoid hemorrhage model.  

PubMed

Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The aim of this study was to assess whether cysteamine prevents post-SAH oxidative stress injury via its antioxidative and anti-apoptotic effects. It was observed that intraperitoneal administration of cysteamine (20 mg/kg/day) could significantly alleviate EBI (including neurobehavioral deficits, brain edema, blood-brain barrier permeability, and cortical neuron apoptosis) after SAH in rats. Meanwhile, cysteamine treatment reduced post-SAH elevated the reactive oxygen species level, the concentration of malondialdehyde, 3-nitrotyrosine, and 8-hydroxydeoxyguanosine and increased the glutathione peroxidase enzymatic activity, the concentration of glutathione and brain-derived neurotrophic factor in brain cortex at 48 h after SAH. These results indicated that administration of cysteamine may ameliorate EBI and provide neuroprotection after SAH in rat models. PMID:25527033

Zhang, Zong-Yong; Yang, Ming-Feng; Wang, Tao; Li, Da-Wei; Liu, Yun-Lin; Zhang, Jin-Hui; Sun, Bao-Liang

2015-05-01

92

Sur gi cal Im prove ment of Brain Edema Re lated to Hy per ten sive Intracerebral Hem or rhage  

Microsoft Academic Search

Back ground. Pa tients with hy per ten sive intracerebral hem or rhage (ICH) are at risk for de layed neu ro log i cal de te ri o ra tion, es pe cially dur ing the sec ond week af ter on set. Mass ef fect due to vasogenic edema caused by ICH has been shown to cause later

Chuan-Fu Huang; Zon-Po Tsai; Cho-Shin Li; Kao-Lun Wang; Yeou-Chih Wang

93

Inhibition of bradykinin receptor B1 protects mice from focal brain injury by reducing blood–brain barrier leakage and inflammation  

PubMed Central

Kinins are proinflammatory and vasoactive peptides that are released during tissue damage and may contribute to neuronal degeneration, inflammation, and edema formation after brain injury by acting on discrete bradykinin receptors, B1R and B2R. We studied the expression of B1R and B2R and the effect of their inhibition on lesion size, blood–brain barrier (BBB) disruption, and inflammatory processes after a focal cryolesion of the right parietal cortex in mice. B1R and B2R gene transcripts were significantly induced in the lesioned hemispheres of wild-type mice (P<0.05). The volume of the cortical lesions and neuronal damage at 24?h after injury in B1R?/? mice were significantly smaller than in wild-type controls (2.5±2.6 versus 11.5±3.9?mm3, P<0.001). Treatment with the B1R antagonist R-715 1?h after lesion induction likewise reduced lesion volume in wild-type mice (2.6±1.4 versus 12.2±6.1?mm3, P<0.001). This was accompanied by a remarkable reduction of BBB disruption and tissue inflammation. In contrast, genetic deletion or pharmacological inhibition of B2R had no significant impact on lesion formation or the development of brain edema. We conclude that B1R inhibition may offer a novel therapeutic strategy after acute brain injuries. PMID:20197781

Raslan, Furat; Schwarz, Tobias; Meuth, Sven G; Austinat, Madeleine; Bader, Michael; Renné, Thomas; Roosen, Klaus; Stoll, Guido; Sirén, Anna-Leena; Kleinschnitz, Christoph

2010-01-01

94

Escin attenuates cerebral edema induced by acute omethoate poisoning.  

PubMed

Organophosphorus exposure affects different organs such as skeletal muscles, the gastrointestinal tract, liver, lung, and brain. The present experiment aimed to evaluate the effect of escin on cerebral edema induced by acute omethoate poisoning. Sprague-Dawley rats were administered subcutaneously with omethoate at a single dose of 60 mg/kg followed by escin treatment. The results showed that escin reduced the brain water content and the amount of Evans blue in omethoate-poisoned animals. Treatment with escin decreased the levels of tumor necrosis factor-alpha (TNF-?), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and prostaglandin E? (PGE?) in the brain. Escin also alleviated the histopathological change induced by acute omethoate poisoning. The findings demonstrated that escin can attenuate cerebral edema induced by acute omethoate poisoning, and the underlying mechanism was associated with ameliorating the permeability of the blood-brain barrier. PMID:21417632

Wang, Tian; Jiang, Na; Han, Bing; Liu, Wenbo; Liu, Tongshen; Fu, Fenghua; Zhao, Delu

2011-06-01

95

Hydrogen Sulfide Offers Neuroprotection on Traumatic Brain Injury in Parallel with Reduced Apoptosis and Autophagy in Mice  

PubMed Central

Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. The present study was undertaken to study the effects of exogenous H2S on traumatic brain injury (TBI) and the underlying mechanisms. The effects of exogenous H2S on TBI were examined by using measurement of brain edema, behavior assessment, propidium iodide (PI) staining, and Western blotting, respectively. Compared to TBI groups, H2S pretreatment had reduced brain edema, improved motor performance and ameliorated performance in Morris water maze test after TBI. Immunoblotting results showed that H2S pretreatment reversed TBI-induced cleavage of caspase-3 and decline of Bcl-2, suppressed LC3-II, Beclin-1 and Vps34 activation and maintained p62 level in injured cortex and hippocampus post TBI. The results suggest a protective effect and therapeutic potential of H2S in the treatment of brain injury and the protective effect against TBI may be associated with regulating apoptosis and autophagy. PMID:24466346

Wang, Tao; Dong, Wenwen; Chen, Xiping; Tao, Luyang

2014-01-01

96

Blood-brain barrier permeability to micromolecules and edema formation in the early phase of incomplete continuous ischemia  

Microsoft Academic Search

The distribution patterns of ionic Lanthanum (La3+; mol.wt. 139) were evaluated after 15, 30 and 60 min of middle cerebral artery occlusion in perfused-fixed rats. Blood-brain barrier (BBB) permeability to Evans blue (EB) and horseradish peroxidase (HRP; mol. wt. 40,000) in vivo was also evaluated. Brain tissue specific gravity was measured. An increase in brain water content was found as

S. Sampaolo; Y. Nakagawa; F. Iannotti; J. Cervos-Navarro; V. Bonavita

1991-01-01

97

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

PubMed

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

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

2015-06-01

98

Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis  

PubMed Central

Background In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synthesis. In this study, we investigated the hypothesis that impaired LNAA influx relates to reduced cerebral protein synthesis. Methods Using positron emission tomography, L-[1-11C]-tyrosine (11C-Tyr) brain influx and incorporation into cerebral protein were studied in 16 PKU patients (median age 24, range 16 – 47 years), most of whom were early and continuously treated. Data were analyzed by regression analyses, using either 11C-Tyr brain influx or 11C-Tyr cerebral protein incorporation as outcome variable. Predictor variables were baseline plasma Phe concentration, Phe tolerance, age, and 11C-Tyr brain efflux. For the modelling of cerebral protein incorporation, 11C-Tyr brain influx was added as a predictor variable. Results 11C-Tyr brain influx was inversely associated with plasma Phe concentrations (median 512, range 233 – 1362 ?mol/L; delta adjusted R2=0.571, p=0.013). In addition, 11C-Tyr brain influx was positively associated with 11C-Tyr brain efflux (delta adjusted R2=0.098, p=0.041). Cerebral protein incorporation was positively associated with 11C-Tyr brain influx (adjusted R2=0.567, p<0.001). All additional associations between predictor and outcome variables were statistically nonsignificant. Conclusions Our data favour the hypothesis that an elevated concentration of Phe in blood reduces cerebral protein synthesis by impairing LNAA transport from blood to brain. Considering the importance of cerebral protein synthesis for adequate brain development and functioning, our results support the notion that PKU treatment be continued in adulthood. Future studies investigating the effects of impaired LNAA transport on cerebral protein synthesis in more detail are indicated. PMID:24007597

2013-01-01

99

Aerobic Fitness Reduces Brain Tissue Loss in Aging Humans  

Microsoft Academic Search

Background. The human brain gradually loses tissue from the third decade of life onward, with concomitant declines in cognitive performance. Given the projected rapid growth in aged populations, and the staggering costs associated with geriatric care, identifying mechanisms that may reduce or reverse cerebral deterioration is rapidly emerging as an important public health goal. Previous research has demonstrated that aerobic

Kirk I. Erickson; Naftali Raz; Andrew G. Webb; Neal J. Cohen; Edward McAuley; Arthur F. Kramer

2003-01-01

100

Astaxanthin reduces ischemic brain injury in adult rats.  

PubMed

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

2009-06-01

101

[Capillary permeability factor produced by C 6 glioma cells: role in peritumoral brain edema and possible mechanism of glucocorticoid action].  

PubMed

We studied whether C6 glioma cells produce a diffusible factor that increases capillary permeability of rat brains. Culture supernatant after 4 hours' incubation of C6 glioma cells in serum-free medium was obtained (SUP-N). SUP-N was concentrated 80-fold by dialysis-concentration (MW cut off was 10 kd) (SUP-C). These two supernatant fractions were tested for capillary permeability activity by their infusion into normal rat brains (right caudate-putamen). Control materials (MEM or concentrated MEM) were also infused into the left caudate-putamen as well as supernatants. Capillary permeability was measured by a quantitative autoradiographic method with 14C-aminoisobutyric acid (AIB) and expressed as an unidirectional blood-to-brain transfer constant (K). Effects of infusates were quantitatively estimated by two parameters, i.e., the highest K value (Kmax) (microliter/g/min) and the spatial extent (D1/2) (mm). The protein concentration of SUP-N and SUP-C was 15 and 950 micrograms/ml, respectively. SUP-N showed a slight increase of capillary permeability, particularly, around the needle track (infusion site) in the brain, but it was not significantly different from the control on the value of Kmax. On the other hand, SUP-C markedly increased capillary permeability (Kmax; SUP-C: 10.83 +/- 0.99, control: 2.53 +/- 0.22, p less than .001) and the effect was much more extensive than that of SUP-N (D1/2; SUP-C: 2.23 +/- 0.26, SUP-N: 0.83 +/- 0.07). A factor in SUP-C increased capillary permeability after a lag phase of 1.5 hours reaching the maximum after 6 hours of infusion, and 24 hours later the effect declined to 30% of Kmax at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2620014

Ohnishi, T; Hayakawa, T; Arita, N; Mogami, H; Ushio, Y; Shapiro, W R

1989-11-01

102

The Maxi-K Channel Opener BMS-204352 Attenuates Regional Cerebral Edema and Neurologic Motor Impairment After Experimental Brain Injury  

Microsoft Academic Search

Large-conductance, calcium-activated potassium (maxi-K) channels regulate neurotransmitter release and neuronal excitability, and openers of these channels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcome after lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized

Jessica A. Cheney; Justin D. Weisser; Florence M. Bareyre; Helmut L. Laurer; Kathryn E. Saatman; Ramesh Raghupathi; Valentin Gribkoff; John E. Starrett; Tracy K. McIntosh

2001-01-01

103

Fluid Balance, Complications, and Brain Tissue Oxygen Tension Monitoring Following Severe Traumatic Brain Injury  

Microsoft Academic Search

Background  Refractory intracranial hypertension (RIH) frequently complicates severe traumatic brain injury (TBI) and is associated with\\u000a worse outcomes. Aggressive fluid resuscitation contributes to the development of peripheral and pulmonary edema, but an effect\\u000a on cerebral edema is not well established. Some clinicians, including advocates of the “Lund Concept”, practice fluid restriction\\u000a as a means of limiting cerebral edema and reducing intracranial

Jeffrey J. Fletcher; Karen Bergman; Paul A. Blostein; Andreas H. Kramer

2010-01-01

104

Edema (Swelling) (Beyond the Basics)  

MedlinePLUS

... Clinical manifestations and diagnosis of edema in adults Idiopathic edema Clinical manifestations and diagnosis of lymphedema Prevention and ... principles of the treatment of edema in adults Idiopathic edema Mechanism of action of diuretics Neurogenic pulmonary edema ...

105

[Uveitic macular edema].  

PubMed

Macular edema may complicate anterior, intermediate, and posterior uveitis, which may be due to various infectious, tumoral, or autoimmune etiologies. Breakdown of the internal or external blood-retinal barrier is involved in the pathogenesis of inflammatory macular edema. Optical coherence tomography has become standard in confirming the diagnosis of macular thickening, due to its non-invasive, reproducible and sensitivity characteristics. Fluorescein and indocyanine green angiography allows for, in addition to study of the macula, screening for associated vasculitis, detection of ischemic areas, easy diagnosis of preretinal, prepaillary or choroidal neovascular complications, and it can provide etiological information and may be required to evaluate the therapeutic response. Treatment of inflammatory macular edema requires specific treatment in cases of infectious or tumoral etiologies. If it remains persistent, or occurs in other etiologies, anti-inflammatory treatments are needed. Steroid treatment, available in intravitreal, subconjunctival and sub-Tenon's routes, are widely used. Limitations of local use include induced cataract and glaucoma, and their short-lasting action. Such products may reveal retinal infection. Thus, bilateral chronic sight-threatening posterior uveitis often requires systemic treatment, and steroids represent the classic first-line therapy. In order to reduce the daily steroid dose, immunosuppressant or immunomodulatory drugs may be added. Certain of these compounds are now available intravitreally. PMID:25547721

Fardeau, C; Champion, E; Massamba, N; LeHoang, P

2015-01-01

106

C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation  

PubMed Central

Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 h. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 h after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted anti-inflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings. PMID:25249935

Albert-Weissenberger, Christiane; Mencl, Stine; Schuhmann, Michael K.; Salur, Irmak; Göb, Eva; Langhauser, Friederike; Hopp, Sarah; Hennig, Nelli; Meuth, Sven G.; Nolte, Marc W.; Sirén, Anna-Leena; Kleinschnitz, Christoph

2014-01-01

107

Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage.  

PubMed

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis. PMID:25042403

Lee, I-Neng; Cheng, Wan-Chun; Chung, Chiu-Yen; Lee, Ming-Hsueh; Lin, Martin Hsiu-Chu; Kuo, Chia-Hui; Weng, Hsu-Huei; Yang, Jen-Tsung

2015-01-01

108

Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?  

PubMed Central

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

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

2014-01-01

109

Acute postobstructive pulmonary edema  

Microsoft Academic Search

Acute postobstructive pulmonary edema may occur after airway obstruction. A decrease in intrathoracic and intraalveolar pressures causes an increased blood flow into the pulmonary vasculature and favors the development of pulmonary edema. Two mechanisms for the development of acute postobstructive pulmonary edema are proposed: type 1 follows acute airway obstruction, and type 2 follows relief of chronic airway obstruction. (OTOLARYNGOL

THOMAS N. GUFFIN; GADY HAR-EL; ABRAHAM SANDERS; FRANK E. LUCENTE; MICHAEL NASH

1995-01-01

110

Cilnidipine induced ankle edema  

PubMed Central

Cilnidipine is a 4th generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema. PMID:24987189

Annil, Vishal R.; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-01-01

111

Cilnidipine induced ankle edema.  

PubMed

Cilnidipine is a 4(th) generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema. PMID:24987189

Annil, Vishal R; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-01-01

112

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

PubMed

Traumatic brain injury (TBI) is a major cause of preventable death and morbidity in young adults. This complex condition is characterized by significant blood brain barrier leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Recovery of function after TBI is partly through neuronal plasticity. In order to test whether treatments that enhance plasticity might improve functional recovery, a controlled cortical impact (CCI) in adult mice, as a model of TBI, in which a controlled cortical impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex, was performed. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family that maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether PEA shows efficacy in a mice model of experimental TBI. PEA treatment is able to reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level further support the efficacy of PEA therapy. The PEA treatment blocked infiltration of astrocytes and restored CCI-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, CD11b and GFAP. PEA inhibited the TBI-mediated decrease in the expression of pJNK and NF-?B. PEA-treated injured animals improved neurobehavioral functions as evaluated by behavioral tests. PMID:22884901

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

2012-11-01

113

Traumatic Brain Injury Reduces Soluble Extracellular Amyloid-? in Mice: A Methodologically Novel Combined Microdialysis- Controlled Cortical Impact Study  

PubMed Central

Acute amyloid-? peptide (A?) deposition has been observed in young traumatic brain injury (TBI) patients, leading to the hypothesis that elevated extracellular A? levels could underlie the increased risk of dementia following TBI. However, a recent microdialysis-based study in human brain injury patients found that extracellular A? dynamics correlate with changes in neurological status. Because neurological status is generally diminished following injury, this correlation suggested the alternative hypothesis that soluble extracellular A? levels may instead be reduced after TBI relative to baseline. We have developed a methodologically novel mouse model that combines experimental controlled cortical impact TBI with intracerebral microdialysis. In this model, we found that A? levels in microdialysates were immediately decreased by 25–50% in the ipsilateral hippocampus following TBI. This result was found in PDAPP, Tg2576, and Tg2576-ApoE2 transgenic mice producing human A? plus wild-type animals. Changes were not due to altered probe function, edema, changes in APP levels, or A? deposition. Similar decreases in A? were observed in phosphate buffered saline-soluble tissue extracts. Hippocampal electroencephalographic activity was also decreased up to 40% following TBI, and correlated with reduced microdialysate A? levels. These results support the alternative hypothesis that post-injury extracellular soluble A? levels are acutely decreased relative to baseline. Reduced neuronal activity may contribute, though the underlying mechanisms have not been definitively determined. Further work will be needed to assess the dynamics of insoluble and oligomeric A? after TBI. PMID:20682338

Schwetye, Katherine E.; Cirrito, John R.; Esparza, Thomas J.; Mac Donald, Christine L.; Holtzman, David M.; Brody, David L.

2010-01-01

114

Reduced predictable information in brain signals in autism spectrum disorder  

PubMed Central

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

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

2014-01-01

115

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

PubMed Central

Background Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Methodology/Principal Findings Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside_significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside_also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Conclusions/Significance Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway. PMID:23029230

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

2012-01-01

116

Mechanisms of astrocyte-mediated cerebral edema.  

PubMed

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

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

2015-02-01

117

Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury.  

PubMed

Excessive production of reactive oxygen species (ROS) after cerebral ischemia and reperfusion is implicated in brain damage through different cellular and molecular mechanisms, and it is further aggravated by impaired cellular antioxidant defense systems under ischemic conditions. Therapeutic strategies based on exogenous delivery of the native form of superoxide dismutase (SOD), a free radical scavenger, are limited because of its short half-life (approximately 6 min) in vivo and poor permeability across the blood-brain-barrier (BBB). We encapsulated SOD in biodegradable poly(D,L-lactide co-glycolide) nanoparticles (SOD-NPs) and tested their efficacy in a rat focal cerebral ischemia-reperfusion injury model. We hypothesized that localized brain delivery of SOD-NPs would sustain the protective effect of SOD by neutralizing the deleterious effects of ROS formed following ischemia-reperfusion. SOD-NPs were administered at the time of reperfusion via the intracarotid route to maximize their localization in the brain. Animals receiving SOD-NPs (10,000 U of SOD/kg) demonstrated a 65% reduction in infarct volume, whereas an equivalent dose of SOD in solution (SOD-Sol) increased it by 25% over saline control (P<0.001; data at 6 h following reperfusion). Control NPs alone or mixed with SOD-Sol were ineffective in reducing infract volume, with results similar to saline control, indicating the protective effect of the encapsulated enzyme. SOD-NPs maintained BBB integrity, thereby preventing edema, reduced the level of ROS formed following reperfusion, and protected neurons from undergoing apoptosis. Animals treated with SOD-NPs demonstrated greater survival than those with saline control (75% vs. 0% at 28 days) and later regained most vital neurological functions. SOD-NPs may be an effective treatment option in conjunction with a thrombolytic agent for stroke patients. PMID:19124559

Reddy, Maram K; Labhasetwar, Vinod

2009-05-01

118

Selective Brain Cooling Reduces Water Turnover in Dehydrated Sheep  

PubMed Central

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

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

2015-01-01

119

Selective brain cooling reduces water turnover in dehydrated sheep.  

PubMed

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

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

2015-01-01

120

Pathophysiology of Macular Edema  

Microsoft Academic Search

Macular edema is defined as an accumulation of fluid in the outer plexiform layer and the inner nuclear layer as well as a swelling of Müller cells of the retina. It consists of a localized expansion of the retinal extracellular space (sometimes associated with the intracellular space) in the macular area. Macular edema is a common cause of a sudden

Stefan Scholl; Janna Kirchhof; Albert J. Augustin

2010-01-01

121

Intravenous anesthetic propofol suppresses prostaglandin E2 and cysteinyl leukotriene production and reduces edema formation in arachidonic acid-induced ear inflammation.  

PubMed

Abstract Propofol is an intravenous drug widely used for anesthesia and sedation. Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have only been demonstrated in vitro, this study sought to ascertain whether similar effects might also be observed in vivo. In the current studies, effects of propofol were tested in a murine model of arachidonic acid-induced ear inflammation. Specifically, propofol - as a pre-treatment -- was intraperitoneally and then topical application of arachidonic acid was performed. After 1?h, tissue biopsies were collected and tested for the presence of edema and for levels of inflammatory mediators. The results indicated that the administration of propofol significantly suppressed ear edema formation, tissue myeloperoxidase activity, and tissue production of both prostaglandin E2 and cysteinyl leukotrienes. From the data, it can be concluded that propofol could exert anti-COX and anti-5-LOX activities in an in vivo model and that these activities in turn could have, at least in part, suppressed arachidonic acid-induced edema formation in the ear. PMID:25046027

Inada, Takefumi; Hirota, Kiichi; Shingu, Koh

2014-07-21

122

Melatonin lowers edema after spinal cord injury  

PubMed Central

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

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

2014-01-01

123

High Altitude Pulmonary Edema  

Microsoft Academic Search

Altitude, speed and mode of ascent and, above all, individual susceptibility are the most important determinants for the occurrence of high-altitude pulmonary edema (HAPE). This illness usually occurs only 2-5 days after acute exposure to altitudes above 2,500-3,000 m. Chest radiographs and CT scans show a patchy predominantly peripheral distribution of edema. Wedge pressure is normal at rest, and there

Peter Bärtsch; Heimo Mairbäurl; Erik R. Swenson; Marco Maggiorini

1997-01-01

124

The lethargic diabetic: cerebral edema in pediatric patients in diabetic ketoacidosis.  

PubMed

Diabetic ketoacidosis (DKA) is the leading cause of hospitalizations for pediatric patients with diabetes mellitus. The most severe complication of DKA is cerebral edema that may lead to brain herniation. We present a case report that highlights the subclinical presentation of DKA-related cerebral edema in a pediatric patient and review the acute care management of suspected cerebral edema during transport. PMID:25733118

Gee, Samantha W

2015-01-01

125

J Neurotrauma . Author manuscript Perfusional deficit and the dynamics of cerebral edemas in experimental  

E-print Network

J Neurotrauma . Author manuscript Page /1 9 Perfusional deficit and the dynamics of cerebral edemas was to characterize edema dynamics, cerebral blood volume and flow alterations in an experimental model of brain there was no evidence of oedma formation. After the initial cytotoxic edema, a clear evolution toward extracellular

Paris-Sud XI, Université de

126

Brain and Heart 1. Reducing your risk of stroke and heart attack. . . . 3  

E-print Network

#12;Contents Brain and Heart 1. Reducing your risk of stroke and heart attack. . . . 3 2. Exercising for a healthy heart . . . . . . . . . . . . . . . . 4 3. Choosing a home blood pressure unit . . . . . . . . . . . . . . . . . 47 #12;BRAIN AND HEART Reducing your risk of stroke and heart attack One of the best ways to protect

Jagannatham, Aditya K.

127

Edema: diagnosis and management.  

PubMed

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. PMID:23939641

Trayes, Kathryn P; Studdiford, James S; Pickle, Sarah; Tully, Amber S

2013-07-15

128

Etanercept Attenuates Traumatic Brain Injury in Rats by Reducing Brain TNF-? Contents and by Stimulating Newly Formed Neurogenesis  

PubMed Central

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF-? and/or stimulating newly formed neurogenesis. Rats that sustained TBI are immediately treated with etanercept. Acute neurological and motor injury is assessed in all rats the day prior to and 7 days after surgery. The numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain injury that occurred during TBI were counted by immunofluorescence staining. Enzyme immunoassay for quantitative determination of TNF-? or etanercept in brain tissues is also performed. Seven days after systemic administration of etanercept, levels of etanercept can be detected in the contused brain tissues. In addition, neurological and motor deficits, cerebral contusion, and increased brain TNF-? contents caused by TBI can be attenuated by etanercept therapy. Furthermore, the increased numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain tissues caused by TBI can be potentiated by etanercept therapy. These findings indicate that systemically administered etanercept may penetrate directly into the contused brain tissues and may improve outcomes of TBI by reducing brain contents of TNF-? and by stimulating newly formed neurogenesis. PMID:23710117

Cheong, Chong-Un; Chao, Chien-Ming; Cheng, Bor-Chih; Yang, Chung-Zhing; Chio, Chung-Ching

2013-01-01

129

Ethanol, not metabolized in brain, significantly reduces brain metabolism, probably via specific GABA(A) receptors  

PubMed Central

Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we used an indirect approach, measuring the effect of alcohol on metabolism of [3-13C]pyruvate in the adult Guinea pig brain cortical tissue slice and comparing the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-13C]ethanol. Ethanol (10, 30 and 60 mM) significantly reduced metabolic flux into all measured isotopomers and reduced all metabolic pool sizes. The metabolic profiles of these three concentrations of ethanol were similar and clustered with that of the ?4?3? positive allosteric modulator DS2 (4-Chloro-N-[2-(2-thienyl)imidazo[1,2a]-pyridin-3-yl]benzamide). Ethanol at a very low concentration (0.1 mM) produced a metabolic profile which clustered with those from inhibitors of GABA uptake, and ligands showing affinity for ?5, and to a lesser extent, ?1-containing GABA(A)R. There was no measureable metabolism of [1,2-13C]ethanol with no significant incorporation of 13C from [1,2-13C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabeled ethanol. The reduction in metabolism seen in the presence of ethanol is therefore likely to be due to its actions at neurotransmitter receptors, particularly ?4?3? receptors, and not because ethanol is substituting as a substrate or because of the effects of ethanol catabolites acetaldehyde or acetate. We suggest that the stimulatory effects of very low concentrations of ethanol are due to release of GABA via GAT1 and the subsequent interaction of this GABA with local ?5-containing, and to a lesser extent, ?1-containing GABA(A)R. PMID:24313287

Rae, Caroline D.; Davidson, Joanne E.; Maher, Anthony D.; Rowlands, Benjamin D.; Kashem, Mohammed A.; Nasrallah, Fatima A.; Rallapalli, Sundari K.; Cook, James M; Balcar, Vladimir J.

2014-01-01

130

Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine  

E-print Network

Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine States of America Abstract Objective: Gender differences in vulnerability for cocaine addiction have been brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers

Homes, Christopher C.

131

Deep Brain Stimulation may Reduce Tremor by Preferential Blockade of Slower Axons via Antidromic Activation  

E-print Network

Deep Brain Stimulation may Reduce Tremor by Preferential Blockade of Slower Axons via Antidromic Abstract-- Deep brain stimulation (DBS) has been used to ameliorate essential and Parkinsonian tremor, however the detailed mechanism by which tremor reduction is achieved remains unclear. We hypothesize

Pearlmutter, Barak

132

Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring  

Microsoft Academic Search

Object. An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is rec- ommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the

Michael F. Stiefel; Alejandro Spiotta; Vincent H. Gracias; Alicia M. Garuffe; Oscar Guillamondegui; Eileen Maloney-Wilensky; Stephanie Bloom; M. Sean Grady; Peter D. LeRoux

2005-01-01

133

Expression of mPGES-1 and IP mRNA is reduced by LLLT in both subplantar and brain tissues in the model of peripheral inflammation induced by carrageenan.  

PubMed

The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw?+?LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw?+?LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm(2) was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP. PMID:24974175

Chagas, Luciene Reginato; Silva, José Antonio; de Almeida Pires, Juliana; Costa, Maricilia S

2015-01-01

134

Reduced Fluorescein Angiography and Fundus Photography Use in the Management of Neovascular Macular Degeneration and Macular Edema During the Past Decade  

PubMed Central

Purpose. We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME). Methods. Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared. Results. From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME. Conclusions. Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes. PMID:24346174

Schneider, Eric W.; Mruthyunjaya, Prithvi; Talwar, Nidhi; Harris Nwanyanwu, Kristen; Nan, Bin; Stein, Joshua D.

2014-01-01

135

Latest advances in edema  

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

136

Acute cardiogenic pulmonary edema  

Microsoft Academic Search

The frequency distribution and severity of the cardiac disease underlying acute cardiogenic pulmonary edema (APE) to define appropriate subsequent diagnostic and management strategies were investigated in 216 consecutive patients. To this effect, the clinical, electrocardiographic, ecocardiographic and angiographic characteristics were analyzed. Coronary artery disease was identified in 185 patients (86%)—146 with acute myocardial infarction—as the underlying cause, isolated valvular disease

Carlos Pena-Gil; Jaume Figueras; Jordi Soler-Soler

2005-01-01

137

RESEARCH Open Access Differential aquaporin 4 expression during edema  

E-print Network

with brain inflammation, with the critical step of edema exacerbation feared in patient care. Water entrance peaking during the active phase. Other examples include severe stroke [2] and brain trauma [3], which Bordeaux, France Full list of author information is available at the end of the article Tourdias et al

Paris-Sud XI, Université de

138

Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat  

Microsoft Academic Search

The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular

J. Y. Jiang; B. G. Lyeth; M. Z. Kapasi; L. W. Jenkins; J. T. Povlishock

1992-01-01

139

Reperfusion pulmonary edema  

SciTech Connect

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

Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. (Harvard Medical School, Boston, MA (USA))

1989-02-17

140

Acute pulmonary edema  

Microsoft Academic Search

Opinion statement  Patients with acute cardiogenic pulmonary edema require rapid assessment and therapy to prevent progression to respiratory\\u000a failure and cardiovascular collapse. The goal of therapy is to decrease the pulmonary capillary wedge pressure by decreasing\\u000a intravascular volume and shifting the blood volume into peripheral vascular beds. Mainstays of therapy include morphine sulfate\\u000a (a venodilator and an anxiolytic), furosemide (a venodilator

Maryl R. Johnson

1999-01-01

141

Pathophysiology and treatment of edema following femoropopliteal bypass surgery.  

PubMed

Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovascular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this edema is not well understood. The Cochrane Library and Medline were used to retrieve literature on edema following peripheral bypass surgery. Factors other than local wound healing alone are suggested in the literature to play a role, given the severity and duration of this edema. Hyperemia, microvascular permeability, reperfusion-associated inflammation and lymphatic disruptions are likely to facilitate the development of edema. Preventive methods could be lymphatic-sparing surgery, intraoperative antioxidative therapy and postoperative elevation. Successful treatment strategies to reduce postoperative edema are based on lymph massage and external compression. In conclusion, the pathophysiology of edema following peripheral surgery is not fully understood, although reperfusion-associated inflammation and lymphatic disruptions are likely to play a crucial role. When future less-invasive techniques prove to be successful, postoperative edema might be minimized. Until then, a careful lymphatic-sparing dissection should be executed when performing a peripheral bypass reconstruction. Postoperatively, the use of compression stockings and leg elevation are currently the golden standards. PMID:22983547

te Slaa, A; Dolmans, D E J G J; Ho, G H; Moll, F L; van der Laan, L

2012-12-01

142

Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury.  

PubMed

Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (A?) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in A? depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI. PMID:24413756

Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V; Sanberg, Paul R; Tan, Jun

2014-01-01

143

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

E-print Network

, the drummers' brain activation was reduced in motor and action representation brain regions when sound matchedAction expertise reduces brain activity for audiovisual matching actions: An fMRI study with expert of Psychology, University of Glasgow, Glasgow, Scotland, UK b Department of Media Technology, Aalborg University

Avanzini, Federico

144

Impaired geranylgeranyltransferase-I regulation reduces membrane-associated Rho protein levels in aged mouse brain.  

PubMed

Synaptic impairment rather than neuronal loss may be the leading cause of cognitive dysfunction in brain aging. Certain small Rho-GTPases are involved in synaptic plasticity, and their dysfunction is associated with brain aging and neurodegeneration. Rho-GTPases undergo prenylation by attachment of geranylgeranylpyrophosphate (GGPP) catalyzed by GGTase-I. We examined age-related changes in the abundance of Rho and Rab proteins in membrane and cytosolic fractions as well as of GGTase-I in brain tissue of 3- and 23-month-old C57BL/6 mice. We report a shift in the cellular localization of Rho-GTPases toward reduced levels of membrane-associated and enhanced cytosolic levels of those proteins in aged mouse brain as compared with younger mice. The age-related reduction in membrane-associated Rho proteins was associated with a reduction in GGTase-I? levels that regulates binding of GGPP to Rho-GTPases. Proteins prenylated by GGTase-II were not reduced in aged brain indicating a specific targeting of GGTase-I in the aged brain. Inhibition of GGTase-I in vitro modeled the effects of aging we observed in vivo. We demonstrate for the first time a decrease in membrane-associated Rho proteins in aged brain in association with down-regulation of GGTase-I?. This down-regulation could be one of the mechanisms causing age-related weakening of synaptic plasticity. PMID:24428713

Afshordel, Sarah; Wood, Wellington Gibson; Igbavboa, Urule; Muller, Walter E; Eckert, Gunter P

2014-05-01

145

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

PubMed

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

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

2015-05-01

146

Pharmacologic modulation of D-49 phospholipase A2-induced paw edema in the mouse.  

PubMed

Paw edema was produced in CD-1 mice by the injection of 0.3 micrograms of snake venom PLA2 (A.p. piscivorus D-49) into the hind paw. Edema peaked at 10 min, remained elevated until 60 min, and then declined slowly. The PLA2 inhibitors, luffariellolide and aristolochic acid, reduced the edema but only when coinjected with the PLA2. The histamine/serotonin antagonists were the most effective drug class against PLA2-induced paw edema. The PAF antagonists, CV-6202 (iv) and kadsurenone (coinjected) reduced the PLA2-induced edema, whereas high doses of the corticosteroids, dexamethasone and hydrocortisone, were also effective. NSAIDs only partially inhibited the paw edema. The LO/CO inhibitors yielded varying activities, with only BW755C and NDGA inhibiting the edema. These results suggest that PLA2 induces paw edema in the mouse via the action of several classes of inflammatory mediators. PMID:2801333

Calhoun, W; Yu, J; Sung, A; Chau, T T; Marshall, L A; Weichman, B M; Carlson, R P

1989-06-01

147

Ischemic preconditioning reduces ischemic brain injury by suppressing nuclear factor kappa B expression and neuronal apoptosis?  

PubMed Central

Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning attenuates ischemic brain damage via inhibiting blood-brain barrier disruption and the inflammatory response. Rats underwent transient (15 minutes) occlusion of the bilateral common carotid artery with 48 hours of reperfusion, and were subjected to permanent middle cerebral artery occlusion. This study explored whether ischemic preconditioning could reduce ischemic brain injury and relevant molecular mechanisms by inhibiting neuronal apoptosis. Results found that at 72 hours following cerebral ischemia, myeloperoxidase activity was enhanced, malondialdehyde levels increased, and neurological function was obviously damaged. Simultaneously, neuronal apoptosis increased, and nuclear factor-?B and cleaved caspase-3 expression was significantly increased in ischemic brain tissues. Ischemic preconditioning reduced the cerebral ischemia-induced inflammatory response, lipid peroxidation, and neurological function injury. In addition, ischemic preconditioning decreased nuclear factor-?B p65 and cleaved caspase-3 expression. These results suggested that ischemic preconditioning plays a protective effect against ischemic brain injury by suppressing the inflammatory response, reducing lipid peroxidation, and neuronal apoptosis via inhibition of nuclear factor-?B and cleaved caspase-3 expression. PMID:25206708

Shi, Songsheng; Yang, Weizhong; Tu, Xiankun; Chen, Chunmei; Wang, Chunhua

2013-01-01

148

Reversible cerebrospinal fluid edema and porencephalic cyst, a rare complication of ventricular catheter.  

PubMed

Cerebrospinal fluid (CSF) edema and porencephaly are rare postoperative complications of a ventricular shunt that result from obstruction of the distal catheter, especially in children with taut ventricles. We report a 10-year-old male with cerebellar germinoma complicated by obstructive hydrocephalus. Ventriculopuncture was performed and an Ommaya reservoir was implanted at the right frontal horn. A distal catheter was initially attached to the reservoir for drainage of hydrocephalus but was later removed. After surgery, multi-agent chemotherapy and radiation therapy, a brain MRI showed CSF edema and porencephaly in the right frontal white matter. These lesions were reduced by prompt removal of the ventricular catheter. It is important to recognize such complications and to remove the catheter as soon as possible, because the brain tissue affected by massive edema may develop irreversible changes. Advanced MRI techniques, including fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging may be helpful for assessing this pathological condition and its prognosis. PMID:20206530

Ozeki, Michio; Funato, Michinori; Teramoto, Takahide; Ohe, Naoyuki; Asano, Takahiko; Kaneko, Hideo; Fukao, Toshiyuki; Kondo, Naomi

2010-05-01

149

Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice.  

PubMed

BackgroundTraumatic brain injury (TBI) induces secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. We recently reported that administration of ATB-346 (2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester), a hydrogen sulfide-releasing cyclooxygenase inhibitor, showed marked beneficial effects in an animal model of spinal cord injury, significantly enhancing recovery of motor function and reducing the secondary inflammation and tissue injury.MethodsHere we evaluated the neuroprotective potential of ATB-346, a hydrogen sulfide-releasing derivative of naproxen, using the controlled cortical impact (CCI) injury model in mice, one of the most common models of TBI. Moreover, the aim of the present study was to carefully investigate molecular pathways and subtypes of glial cells involved in the protective effect of ATB-346 on inflammatory reaction associated with an experimental model of TBI. In these studies, TBI was induced in mice by CCI and mice were orally administered ATB-346, naproxen (both at 30 ¿mol/kg) or vehicle (dimethylsulfoxide:1% carboxymethylcellulose [5:95] suspension) one and six hours after brain trauma and once daily for 10 days.ResultsResults revealed that ATB-346 attenuated TBI-induced brain edema, suppressed TBI-induced neural cell death and improved neurological function. ATB-346 also significantly reduced the severity of inflammation and restored neurotrophic factors that characterized the secondary events of TBI.ConclusionsThese data demonstrate that ATB-346 can be efficacious in a TBI animal model by reducing the secondary inflammation and tissue injury. Therefore, ATB-346 could represent an interesting approach for the management of secondary damage following CNS diseases, counteracting behavioral changes and inflammatory process. PMID:25472548

Campolo, Michela; Esposito, Emanuela; Ahmad, Akbar; Di Paola, Rosanna; Paterniti, Irene; Cordaro, Marika; Bruschetta, Giuseppe; Wallace, John L; Cuzzocrea, Salvatore

2014-12-01

150

Multifunctional Liposomes Reduce Brain ?-Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models  

PubMed Central

Alzheimer's disease is characterized by the accumulation and deposition of plaques of ?-amyloid (A?) peptide in the brain. Given its pivotal role, new therapies targeting A? are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of A? assemblies and evaluated their efficiency in reducing the A? burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood–brain barrier targeting and with phosphatidic acid for A? binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, A? assemblies in vitro (EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble A?1–42 (?33%), assessed by ELISA, and the number and total area of plaques (?34%) detected histologically. Also, brain A? oligomers were reduced (?70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [11C]Pittsburgh compound B (PIB). The reduction of brain A? was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain A? aggregates and promote peptide removal across the blood–brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease. PMID:25319699

Balducci, Claudia; Mancini, Simona; Minniti, Stefania; La Vitola, Pietro; Zotti, Margherita; Sancini, Giulio; Mauri, Mario; Cagnotto, Alfredo; Colombo, Laura; Fiordaliso, Fabio; Grigoli, Emanuele; Salmona, Mario; Snellman, Anniina; Haaparanta-Solin, Merja; Forloni, Gianluigi; Re, Francesca

2014-01-01

151

Influence of moderate hypothermia on ischemic brain damage incurred under hyperglycemic conditions  

Microsoft Academic Search

Preischemic hyperglycemia aggravates brain damage following transient ischemia, and adds some special features to the damage incurred, notably a high frequency of postischemic seizures, cellular edema, and affectation of additional brain structures, such as the substanta nigra pars reticulata (SNPR). We raised the question whether mild intra-ischemic hypothermia (32–33° C), known to reduce selective neuronal vulnerability in normoglycemic subjects, also

J. Lundgren; M.-L. Smith; B. K. Siesjö

1991-01-01

152

Cerebral embolism: local CFBF and edema measured by CT scanning and Xe inhalation. [Baboons  

SciTech Connect

Serial CT scans were made in baboons after cerebral embolization during stable Xe inhalation for measuring local values for CBF and lambda (brain-blood partition or solubility coefficients), followed by iodine infusion for detecting blood-brain barrier (BBB) damage. Persistent zones of zero flow surrounded by reduced flow were measured predominantly in subcortical regions, which showed gross and microscopic evidence of infarction at necropsy. Overlying cortex was relatively spared. Reduced lambda values attributed to edema appeared within 3 to 5 minutes and progressed up to 60 minutes. Damage to BBB with visible transvascular seepage of iodine began to appear 1 to 1 1/2 hours after embolism. In chronic animals, lambda values were persistently reduced in areas showing histologic infarction. Contralateral hemispheric CBF increased for the first 15 minutes after embolism, followed by progressive reduction after 30 minutes (diaschisis).

Meyer, J.S.; Yamamoto, M.; Hayman, L.A.; Sakai, F.; Nakajima, S.; Armstrong, D.

1980-01-01

153

Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.  

PubMed

Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD. PMID:24463179

Zhang, Huizhen; Guo, Shang; Zhang, Linlin; Jia, Liting; Zhang, Zhan; Duan, Hongbao; Zhang, Jingbin; Liu, Jingyan; Zhang, Weidong

2014-03-15

154

Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans.  

PubMed

Fetal growth retardation (FGR) is a critical problem in the neonatal period, because a substantial population of infants born with FGR go on to develop various developmental disorders. In the present study, we produced FGR model rats by continuous administration of a synthetic thromboxane A2 analogue (STA2) to pregnant rats. The FGR pups exhibited a significant delay in postnatal neurological development. Moreover, behavioral analyses revealed the presence of a learning disability in juvenile FGR male rats. To investigate the mechanism underlying the neurological disorders, histological and biochemical analyses of the brain of FGR rats were performed. The density of neurons in the cortical plate of an FGR brain was low compared with the brains of a similarly aged, healthy rat. Consistent with this finding, the density of TUNEL-positive cells was higher in the cortical plate of FGR brains. Western blot analyses showed that the levels of three brain-specific chondroitin sulfate proteoglycans (CSPGs), neurocan, phosphacan, and neuroglycan C, were all significantly reduced in the brain of neonatal FGR rats compared with those of the control. The reduction of CSPG-levels and morphological changes in the brain may be relevant to neurological dysfunction in FGR. PMID:19393646

Saito, Akiko; Matsui, Fumiko; Hayashi, Kanako; Watanabe, Kimi; Ichinohashi, Yuko; Sato, Yoshiaki; Hayakawa, Masahiro; Kojima, Seiji; Oohira, Atsuhiko

2009-09-01

155

Effect of baicalin on matrix metalloproteinase-9 expression and blood-brain barrier permeability following focal cerebral ischemia in rats.  

PubMed

Focal cerebral ischemia results in an increased expression of matrix metalloproteinase-9 (MMP-9), which induces vasogenic brain edema via disrupting the blood-brain barrier (BBB) integrity. Recent studies from our laboratory showed that baicalin reduces ischemic brain damage by inhibiting inflammatory reaction and neuronal apoptosis in a rat model of focal cerebral ischemia. In the present study, we first explored the effect of baicalin on the neuronal damage, brain edema and BBB permeability, then further investigated its potential mechanisms. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administrated by intraperitoneally injected twice at 2 and 12 h after the onset of MCAO. Neuronal damage, brain edema and BBB permeability were measured 24 h following MCAO. Expression of MMP-9 protein and mRNA were determined by western blot and RT-PCR, respectively. Expression of tight junction protein (TJP) occludin was detected by western blot. Neuronal damage, brain edema and BBB permeability were significantly reduced by baicalin administration following focal cerebral ischemia. Elevated expression of MMP-9 protein and mRNA were significantly down-regulated by baicalin administration. In addition, MCAO caused the decreased expression of occludin, which was significantly up-regulated by baicalin administration. Our study suggested that baicalin reduces MCAO-induced neuronal damage, brain edema and BBB permeability, which might be associated with the inhibition of MMP-9 expression and MMP-9-mediated occludin degradation. PMID:21678122

Tu, Xian-kun; Yang, Wei-zhong; Liang, Ri-sheng; Shi, Song-sheng; Chen, Jian-ping; Chen, Chun-mei; Wang, Chun-hua; Xie, Hai-shu; Chen, Yan; Ouyang, Long-qiang

2011-11-01

156

Antenatal allopurinol reduces hippocampal brain damage after acute birth asphyxia in late gestation fetal sheep.  

PubMed

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

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

2014-02-01

157

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

PubMed Central

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

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

2012-01-01

158

Amantadine induced reversible corneal edema.  

PubMed

Amantadine is becoming more commonly used for Parkinson's disease (PD), particularly for its efficacy in treating the drug-induced dyskinesias. Corneal edema is a known but unusual side effect of amantadine therapy, rarely reported in the neurological literature. We report amantadine-induced reversible corneal edema in a patient with advanced PD. PMID:21163653

Deogaonkar, Milind; Wilson, Kathy; Vitek, Jerrold

2011-02-01

159

Pulmonary edema induced by laryngospasm  

Microsoft Academic Search

Although pulmonay edema has many causes, acute airway obstruction is rarely mentioned as one of them because of its infrequent occurrence. We describe a case of laryngospasm, which was complicated by the development of pulmonary edema. We discuss the pathophysiologic consequences of acute airway obstruction leading to this complication.

Atsuko Kobayashi; Rokurou Shiba; Mitsuyoshi Lee; Yoshifumi Tanaka

1993-01-01

160

[How to quantify limb edema?].  

PubMed

Edema of venous or lymphatic origin is frequently encountered in vasculopathies. Clinical diagnosis is readily made but precise quantification of edema is difficult. Various procedures have been proposed to quantify edema volume or analyze its composition. Water volumetry remains the gold standard but volumetry calculated with formulas from circumferential measurements for a cylinder or frustum methods are reproducible with high interrater and intrarater reliability. Automated measurement systems are expensive and reserved for research. Ideally, volume measurements for a given patient during the follow-up should be made by the same practitioner using the same method because the different methods are not interchangeable. Notably, edema composition can be evaluated by high frequency ultrasound, CT-scan, MRI or bioimpedance. Edema quantification is essential during patient follow-up and the method to be used depends on the objectives to be met. PMID:20363084

Boulon, C; Becker, F; Vignes, S

2010-06-01

161

Edema and elasticity of a fronto-temporal decompressive craniectomy  

PubMed Central

Background: Decompressive craniectomy is undertaken for relief of brain herniation caused by acute brain swelling. Brain stiffness can be estimated by palpating the decompressive cranial defect and can provide some relatively subjective information to the neurosurgeon to help guide care. The goal of the present study was to objectively evaluate transcutaneous stiffness of the cranial defect using a tactile resonance sensor and to describe the values in patients with a decompressive window in order to characterize the clinical association between brain edema and stiffness. Methods: Data were prospectively collected from 13 of 37 patients who underwent a decompressive craniectomy in our hospital during a 5-year period. Transcutaneous stiffness was measured as change in frequency and as elastic modulus. Results: Stiffness variables of the decompressive site were measured without any adverse effect and subsequent calculations revealed change in frequency = 101.71 ± 36.42 Hz, and shear elastic modulus = 1.99 ± 1.11 kPa. Conclusions: The elasticity of stiffness of a decompressive site correlated with brain edema, cisternal cerebrospinal fluid pressure, and brain shift, all of which are related to acute brain edema. PMID:22347679

Takada, Daikei; Nagai, Hidemasa; Moritake, Kouzo; Akiyama, Yasuhiko

2012-01-01

162

Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury  

PubMed Central

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury. PMID:25546517

Xiao, Ai-Jiao; Chen, Wenliang; Xu, Baofeng; Liu, Rui; Turlova, Ekaterina; Barszczyk, Andrew; Sun, Christopher Lf; Liu, Ling; Deurloo, Marielle; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

2014-01-01

163

Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.  

PubMed

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury. PMID:25546517

Xiao, Ai-Jiao; Chen, Wenliang; Xu, Baofeng; Liu, Rui; Turlova, Ekaterina; Barszczyk, Andrew; Sun, Christopher Lf; Liu, Ling; Deurloo, Marielle; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

2015-01-01

164

Approximation error method can reduce artifacts due to scalp blood flow in optical brain activation imaging  

NASA Astrophysics Data System (ADS)

Diffuse optical tomography can image the hemodynamic response to an activation in the human brain by measuring changes in optical absorption of near-infrared light. Since optodes placed on the scalp are used, the measurements are very sensitive to changes in optical attenuation in the scalp, making optical brain activation imaging susceptible to artifacts due to effects of systemic circulation and local circulation of the scalp. We propose to use the Bayesian approximation error approach to reduce these artifacts. The feasibility of the approach is evaluated using simulated brain activations. When a localized cortical activation occurs simultaneously with changes in the scalp blood flow, these changes can mask the cortical activity causing spurious artifacts. We show that the proposed approach is able to recover from these artifacts even when the nominal tissue properties are not well known.

Heiskala, Juha; Kolehmainen, Ville; Tarvainen, Tanja; Kaipio, Jari. P.; Arridge, Simon R.

2012-09-01

165

Approximation error method can reduce artifacts due to scalp blood flow in optical brain activation imaging.  

PubMed

Diffuse optical tomography can image the hemodynamic response to an activation in the human brain by measuring changes in optical absorption of near-infrared light. Since optodes placed on the scalp are used, the measurements are very sensitive to changes in optical attenuation in the scalp, making optical brain activation imaging susceptible to artifacts due to effects of systemic circulation and local circulation of the scalp. We propose to use the Bayesian approximation error approach to reduce these artifacts. The feasibility of the approach is evaluated using simulated brain activations. When a localized cortical activation occurs simultaneously with changes in the scalp blood flow, these changes can mask the cortical activity causing spurious artifacts. We show that the proposed approach is able to recover from these artifacts even when the nominal tissue properties are not well known. PMID:23085913

Heiskala, Juha; Kolehmainen, Ville; Tarvainen, Tanja; Kaipio, Jari P; Arridge, Simon R

2012-09-01

166

Perspectives on Neonatal Hypoxia\\/Ischemia-Induced Edema Formation  

Microsoft Academic Search

Neonatal hypoxia\\/ischemia (HI) is the most common cause of developmental neurological, cognitive and behavioral deficits in\\u000a children, with hyperoxia (HHI) treatment being a clinical therapy for newborn resuscitation. Although cerebral edema is a\\u000a common outcome after HI, the mechanisms leading to excessive fluid accumulation in the brain are poorly understood. Given\\u000a the rigid nature of the bone-encased brain matter, knowledge

Diana Carolina Ferrari; Olivera Nesic; Jose Regino Perez-Polo

2010-01-01

167

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

PubMed Central

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

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

2014-01-01

168

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

E-print Network

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

Shair, Kamal A. (Kamal Abdo)

2010-01-01

169

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

PubMed Central

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

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

2014-01-01

170

Acupuncture at Baihui and Dazhui reduces brain cell apoptosis in heroin readdicts.  

PubMed

Acupuncture at Baihui (GV20) and Dazhui (GV14) reduces neuronal loss and attenuates ultrastructural damage in cerebral ischemic rats. However, whether acupuncture can treat addiction and prevent readdiction through changes to brain cell ultrastructure remains unknown. In this study, cell apoptosis was observed in the hippocampus and frontal lobe of heroin readdicted rats by electron microscopy. Immunohistochemical staining displayed a reduction in Bcl-2 expression and an increase in Bax expression in the hippocampus and frontal lobe. After rats were given acupuncture at Baihui and Dazhui, the pathological damage in the hippocampus and frontal lobe was significantly reduced, Bcl-2 expression was upregulated and Bax expression was downregulated. Acupuncture exerted a similar effect with methadone, a commonly used drug for clinical treatment of drug addiction. Experimental findings suggest that acupuncture at Dazhui and Baihui can prevent brain cell apoptosis in heroin readdicted rats. PMID:25206797

Hou, Xiaorong; Zhang, Rongjun; Lv, Hang; Cai, Xinghui; Xie, Guangchuan; Song, Xiaoge

2014-01-15

171

High-Altitude Pulmonary Edema  

Microsoft Academic Search

\\u000a High-altitude pulmonary edema (HAPE) is an uncommon form of pulmonary edema that occurs in healthy individuals within a few\\u000a days of arrival at altitudes above 2,500–3,000 m. The crucial pathophysiology is an excessive hypoxia-mediated rise in pulmonary\\u000a vascular resistance (PVR) or hypoxic pulmonary vasoconstriction (HPV) leading to increased microvascular hydrostatic pressures\\u000a despite normal left atrial pressure. The resultant hydrostatic stress

Erik R. Swenson

172

Pulmonary Edema in Myasthenic Crisis  

PubMed Central

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

Anand, Uttara Swati; Arulneyam, Jayanthi

2013-01-01

173

N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours  

PubMed Central

Abnormalities in glycosphingolipid (GSL) biosynthesis have been implicated in the oncogenesis and malignancy of brain tumours. GSLs comprise the gangliosides and the neutral GSLs and are major components of the cell surface glycocalyx. N -butyldeoxynojirimycin (N B-DNJ) is an imino sugar that inhibits the glucosyltransferase catalysing the first step in GSL biosynthesis. The influence of N B-DNJ was studied on the growth and ganglioside composition of two 20-methylcholanthrene-induced experimental mouse brain tumours, EPEN and CT-2A, which were grown in vitro and in vivo. N B-DNJ (200??M) inhibited the proliferation of the EPEN and CT-2A cells by 50%, but did not reduce cell viability. The drug, administered in the diet (2400?mg kg?1) to adult syngeneic C57BL/6 mice, reduced the growth and ganglioside content of subcutaneous and intracerebral EPEN and CT-2A tumours by at least 50% compared to the untreated controls. N B-DNJ treatment also shifted the relative distribution of tumour gangliosides in accordance with the depletion of metabolic substrates. Side effects of N B-DNJ treatment were generally mild and included reductions in body and spleen weights and intestinal distension. We conclude that N B-DNJ may inhibit tumour growth through an effect on ganglioside biosynthesis and may be useful as a new chemotherapy for brain tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11308262

Ranes, M K; El-Abbadi, M; Manfredi, M G; Mukherjee, P; Platt, F M; Seyfried, T N

2001-01-01

174

Dosimetric Predictors of Laryngeal Edema  

SciTech Connect

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

Sanguineti, Giuseppe [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States)]. E-mail: gisangui@utmb.edu; Adapala, Prashanth [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States); Endres, Eugene J. C [Department of Medical Physics, University of Texas Medical Branch, Galveston, TX (United States); Brack, Collin [Department of Medical Physics, University of Texas Medical Branch, Galveston, TX (United States); Fiorino, Claudio [Department of Physics, Ospedale San Raffaele, Milan (Italy); Sormani, Maria Pia [Biostatistics Unit, University of Genoa, Genoa (Italy); Parker, Brent [Department of Medical Physics, University of Texas Medical Branch, Galveston, TX (United States)

2007-07-01

175

Impaired brain development and reduced cognitive function in phospholipase D-deficient mice.  

PubMed

The phospholipases D (PLD1 and 2) are signaling enzymes that catalyze the hydrolysis of phosphatidylcholine to phosphatidic acid, a lipid second messenger involved in cell proliferation, and choline, a precursor of acetylcholine (ACh). In the present study, we investigated development and cognitive function in mice that were deficient for PLD1, or PLD2, or both. We found that PLD-deficient mice had reduced brain growth at 14-27 days post partum when compared to wild-type mice. In adult PLD-deficient mice, cognitive function was impaired in social and object recognition tasks. Using brain microdialysis, we found that wild-type mice responded with a 4-fold increase of hippocampal ACh release upon behavioral stimulation in the open field, while PLD-deficient mice released significantly less ACh. These results may be relevant for cognitive dysfunctions observed in fetal alcohol syndrome and in Alzheimer' disease. PMID:24813107

Burkhardt, Ute; Stegner, David; Hattingen, Elke; Beyer, Sandra; Nieswandt, Bernhard; Klein, Jochen

2014-06-20

176

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

PubMed Central

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

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

2015-01-01

177

Brain  

MedlinePLUS

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

178

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

PubMed Central

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

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

2015-01-01

179

Acute Cardiogenic Pulmonary Edema: Clinical and Noninvasive Evaluation  

Microsoft Academic Search

Left ventricular echocardiograms performed within ninety-six hours of ad mission were prospectively correlated with the clinical course in 87 consecutive patients admitted with acute pulmonary edema. Patients were stratified into four groups based on their two-dimensional echocardiogram: hyperdynamic, normal, mildly reduced, and severely reduced. Echocardiographic estimates of left ventricular function were compared with their ejection fraction measured by the gated

Alan J. Bier; Peter Q. Eichacker; Lawrence I. Sinoway; Sachiko M. Terribile; Joel A. Strom; Deborah L. Keefe

1988-01-01

180

Preoperative mucosal tolerance to brain antigens and a neuroprotective immune response following surgical brain injury  

PubMed Central

Object Intracranial surgery causes cortical injury from incisions, hemorrhage, retraction, and electrocautery. The term “surgical brain injury” (SBI) has been developed to categorize this injury inherent to the procedure. Neuroinflammation plays a significant role in SBI. Traditional antiinflammatory therapies are often limited by their immunosuppressive side effects and poor CNS penetration. This study uses mucosal tolerance to develop an immune system that is tolerant to brain myelin basic protein (MBP) so that inflammation can be suppressed in a timely and site-specific manner following surgical disruption of the blood-brain barrier. Methods A standard SBI model using CD57 mice was used. Nasopharyngeal mucosa was exposed to vehicle, ovalbumin, or MBP to develop mucosal tolerance to these antigens. Immunological tolerance to MBP was confirmed in vivo through hypersensitivity testing. Neurological scores, cerebral edema, and interleukin (IL)–1? and transforming growth factor (TGF)–?1 cytokine levels were measured 48 hours postoperatively. Results Hypersensitivity testing confirmed the development of immune tolerance to MBP. Myelin basic protein– tolerant mice demonstrated reduced neurological injury, less cerebral edema, decreased levels of IL-1?, and increased levels of TGF?1 following SBI. Conclusions Developing preoperative immunological tolerance to brain antigens through mucosal tolerance provides neuroprotection, reduces brain edema, and modulates neuroinflammation following SBI. PMID:22017304

Ayer, Robert E.; Jafarian, Nazanin; Chen, Wanqiu; Applegate, Richard L.; Colohan, Austin R. T.; Zhang, John H.

2015-01-01

181

Vasogenic Edema of the Basal Ganglia after Intra-Arterial Administration of Nimodipine for Treatment of Vasospasm  

PubMed Central

The intra-arterial administration of nimodipine (IAN) is commonly used for cerebral vasospasm refractory to medical treatments. We report two cases of vasogenic edema after IAN. Our patients with aneurismal subarachnoid hemorrhage presented with vasospasm, which was treated by IAN. Consequently, vasogenic edema developed in the basal ganglia. Reperfusion following IAN for vasospasm may have the potential for inciting vasogenic edema in the ischemic brain. PMID:21519500

Ryu, Chang-Woo; Yu, Seung-Young; Kim, Eui-Jong

2011-01-01

182

Massive mesenteric edema in a patient with type I hereditary angioedema.  

PubMed

We report a patient with hereditary angioedema (HAE) presenting with skin edema and abdominal pain. Laboratory examination showed reduced levels of CH50, C2, C4, and C1 inhibitor (C1-INH). Abdominal computed tomography (CT) showed marked mesenteric edema and wall thickening of the duodenum and transverse colon. Acute abdominal pain is common in HAE and is difficult to distinguish from surgical emergency. Massive mesenteric edema on CT is a rare, but specific, sign suggesting HAE. PMID:17029094

Sekijima, Yoshiki; Hashimoto, Takao; Koshihara, Hiroshi; Kawachi, Yasuhiro; Otsuka, Fujio; Ikeda, Shu-ichi

2005-01-01

183

Prenatal alcohol exposure reduces magnetic susceptibility contrast and anisotropy in the white matter of mouse brains.  

PubMed

Prenatal alcohol exposure can result in long-term cognitive and behavioral deficits. Fetal alcohol spectrum disorder (FASD) refers to a range of permanent birth defects caused by prenatal alcohol exposure, and is the most common neurodevelopmental disorder in the US. Studies by autopsy and conventional structural MRI indicate that the midline structures of the brain are particularly vulnerable to prenatal alcohol exposure. Diffusion tensor imaging (DTI) has shown that abnormalities in brain white matter especially the corpus callosum are very common in FASD. Quantitative susceptibility mapping (QSM) is a novel technique that measures tissue's magnetic property. Such magnetic property is affected by tissue microstructure and molecular composition including that of myelin in the white matter. In this work, we studied three major white matter fiber bundles of a mouse model of FASD and compared it to control mice using both QSM and DTI. QSM revealed clear and significant abnormalities in anterior commissure, corpus callosum, and hippocampal commissure, which were likely due to reduced myelination. Our data also suggested that QSM may be even more sensitive than DTI for examining changes due to prenatal alcohol exposure. Although this is a preclinical study, the technique of QSM is readily translatable to human brain. PMID:25175539

Cao, Wei; Li, Wei; Han, Hui; O'Leary-Moore, Shonagh K; Sulik, Kathleen K; Allan Johnson, G; Liu, Chunlei

2014-11-15

184

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

PubMed

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

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

2015-03-01

185

Effect of lavender oil (Lavandula angustifolia) on cerebral edema and its possible mechanisms in an experimental model of stroke.  

PubMed

Lavender belongs to the family Labiatae and has a variety of cosmetic uses as well as therapeutic purposes in herbal medicine. The present study was conducted to evaluate the protective effect of lavender oil against brain edema and its possible mechanisms in an experimental model of stroke. Under Laser-Doppler Flowmetry, focal cerebral ischemia was induced by the transient occlusion of the middle cerebral artery for 1h in rats. Lavender oil (100, 200, and 400 mg/kg ip (and/or vehicle was injected at the onset of ischemia. Infarct size, cerebral edema, functional outcome, and oxidative stress biomarkers were evaluated using standard methods. Western blotting was used to determine the protein expression of VEGF, Bax, and Bcl-2. Treatment with lavender oil at doses of 200 and 400 mg/kg significantly diminished infarct size, brain edema, and improved functional outcome after cerebral ischemia (P<0.001). Lavender oil (200 mg/kg) also reduced the content of malondialdehyde and increased the activities of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity (P<0.001). Although lavender oil enhanced VEGF expression (P=0.026), it could not decrease the Bax-to-Bcl-2 ratio (pro- to anti-apoptotic proteins) in the rat brain (P>0.05). The results indicated that lavender oil has neuroprotective activity against cerebral ischemia and alleviated neurological function in rats, and the mechanism may be related to augmentation in endogenous antioxidant defense, inhibiting oxidative stress, and increasing VEGF expression in the rat brain. However, lavender oil could not suppress the apoptosis pathway. PMID:24384140

Vakili, Abedin; Sharifat, Shaghayegh; Akhavan, Maziar Mohammad; Bandegi, Ahmad Reza

2014-02-22

186

Edema: a silent but important factor.  

PubMed

Edema is a normal response to injury. Even the smallest injury is associated with some inflammation, and initial edema is part of the normal inflammatory process. However, edema becomes a concern when it persists beyond the inflammatory phase. Once we have progressed into the rebuilding, or fibroplastic phase of healing, edema will delay healing and contribute to complications such as pain and stiffness. Early prevention and management to prevent this progression are therefore critical. This article discusses edema in relation to stages of healing and presents the research behind techniques available to the clinician to manage localized extracellular upper extremity edema in the patient with an intact lymphatic system. PMID:22212492

Villeco, June P

2012-01-01

187

Reduced brain cortical folding in schizophrenia revealed in two independent samples.  

PubMed

The cerebral cortex is highly convoluted, and principal folding patterns are determined early in life. Degree of cortical folding in adult life may index aberrations in brain development. Results from previous studies of cortical folding in schizophrenia are inconsistent. Here we investigated cortical folding patterns in the hitherto largest sample of patients with schizophrenia drawn from two independent cohorts. Magnetic resonance imaging scans were acquired from 207 patients and 206 healthy subjects recruited to two separate research projects in Sweden and Norway. Local gyrification index (lGI) was estimated continuously across the cortex using automated methods. Group differences in lGI were analyzed using general linear models. Patients had lower lGI in three large clusters of the cortex with peak differences found in the left precentral gyrus, right middle temporal gyrus, and right precuneus. Similar, although not completely overlapping results were found when the two cohorts were analyzed separately. There were no significant interaction effects between age and diagnosis and gender and diagnosis. The finding of reduced degree of folding in large regions of the cerebral cortex across two independent samples indicates that reduced gyrification is an inherent feature of the brain pathology in schizophrenia. PMID:24365403

Nesvåg, Ragnar; Schaer, Marie; Haukvik, Unn K; Westlye, Lars T; Rimol, Lars M; Lange, Elisabeth H; Hartberg, Cecilie B; Ottet, Marie-Christine; Melle, Ingrid; Andreassen, Ole A; Jönsson, Erik G; Agartz, Ingrid; Eliez, Stephan

2014-02-01

188

Molecular Mechanisms of Ischemic Cerebral Edema: Role of Electroneutral Ion Transport  

NSDL National Science Digital Library

The brain achieves homeostasis of its intracellular and extracellular fluids by precisely regulating the transport of solute and water across its major cellular barriers: endothelia of the blood-brain barrier (BBB), choroid plexus epithelia, and neuroglial cell membranes. Cerebral edema, the pathological accumulation of fluid in the brainÂ?s intracellular and extracellular spaces, is a major cause of morbidity and mortality following stroke and other forms of ischemic brain injury. Until recently, mechanisms of cerebral edema formation have been obscure; consequently, its treatment has been empiric and suboptimal. Here, we provide a paradigm for understanding ischemic cerebral edema, showing that its molecular pathogenesis is a complex yet step-wise process that results largely from impaired astrocytic cell volume regulation and permeability alterations in the cerebral microvasculature, both of which arise from pathological changes in the activities of specific ion channels and transporters. Recent data has implicated the bumetanide-sensitive NKCC1, an electroneutral cotransporter expressed in astrocytes and the BBB, in cerebral edema formation in several different rodent models of stroke. Pharmacological inhibition or genetic deficiency of NKCC1 decreases ischemia-induced cell swelling, BBB breakdown, cerebral edema, and neurotoxicity. Combination pharmacological strategies that include NKCC1 as a target might thus prove beneficial for the treatment of ischemic, and potentially other types of, cerebral edema.

Kristopher Kahle (Massachusetts General Hospital and Harvard Medical School Neurosurgery)

2009-08-01

189

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury  

PubMed Central

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

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

2014-01-01

190

Synthetic Ground Truth for Validation of Brain Tumor MRI Segmentation  

E-print Network

-modal 3D brain MRI with tumor and edema, along with the ground truth. Tumor mass effect is modeled using a biomechanical model, while tumor and edema infiltration is mod- eled as a reaction-diffusion process is typically not done since manual segmentation of edema or of the whole brain are very challenging tasks

191

Synthetic Ground Truth for Validation of Brain Tumor MRI Segmentation  

E-print Network

method for generating synthetic multi-modal 3D brain MRI with tumor and edema, along with the ground truth. Tumor mass effect is modeled using a biomechanical model, while tumor and edema infiltration is typically not done since manual segmentation of edema or of the whole brain are very challenging tasks

Prastawa, Marcel

192

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

SciTech Connect

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

Chang, Eric L. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States)]. E-mail: echang@mdanderson.org; Akyurek, Serap [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Avalos, Tedde C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Rebueno, Neal C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Spicer, Chris C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Garcia, John C [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Famiglietti, Robin [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Chao, K.S. Clifford [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Mahajan, Anita [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Woo, Shiao Y. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States); Maor, Moshe H. [Department of Radiation Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX (United States)

2007-05-01

193

Contributions of Histamine, Prostanoids, and Neurokinins to Edema Elicited by Edema Toxin from Bacillus anthracis  

Microsoft Academic Search

Bacillus anthracis edema toxin (ET), composed of protective antigen and an adenylate cyclase edema factor (EF), elicits edema in host tissues, but the target cells and events leading from EF-mediated cyclic-AMP production to edema are unknown. We evaluated the direct effect of ET on several cell types in vitro and tested the possibility that mediators of vascular leakage, such as

Jeffrey Tessier; Candace Green; Diana Padgett; Wei Zhao; Lawrence Schwartz; Molly Hughes; Erik Hewlett

2007-01-01

194

Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study  

PubMed Central

Background Previous Magnetic Resonance Imaging (MRI) studies of people with anorexia nervosa (AN) have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume. Methods Voxel based morphometry (VBM), corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN) and 21 women (HC) was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS). Results Increased right dorsolateral prefrontal cortex (DLPFC) and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN. Conclusions In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders. PMID:22093442

2011-01-01

195

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

SciTech Connect

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

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

1987-01-01

196

Anti-tau antibody reduces insoluble tau and decreases brain atrophy  

PubMed Central

Objective We previously found a strong reduction in tau pathology and insoluble tau in P301S tau transgenic mice following intracerebroventricular infusion of the anti-tau antibody HJ8.5. We sought to determine the effects of HJ8.5 in the same model following peripheral administration. Methods The primary objective was to determine if HJ8.5 administered at a dose of 50 mg kg?1 week?1 by intraperitoneal (IP) injection to 6-month-old P301S mice for 3 months would influence phospho-tau (p-tau) accumulation, tau insolubility, and neurodegeneration. Results Treatment with HJ8.5 at 50 mg/kg showed a very strong decrease in detergent-insoluble tau. Importantly, HJ8.5 significantly reduced the loss of cortical and hippocampal tissue volumes compared to control treated mice. HJ8.5 treatment reduced hippocampal CA1 cellular layer staining with the p-tau antibody AT8 and thio-S-positive tau aggregates in piriform cortex and amygdala. Moreover, mice treated with HJ8.5 at 50 mg/kg showed a decrease in motor/sensorimotor deficits compared to vehicle-treated mice. Some effects of HJ8.5, including reduction in brain atrophy, and p-tau immunostaining were also seen with a dose of 10 mg kg?1 week?1. In BV2-microglial cells, we observed significantly higher uptake of P301S tau aggregates in the presence of HJ8.5. HJ8.5 treatment also resulted in a large dose-dependent increase of tau in the plasma. Interpretation Our results indicate that systemically administered anti-tau antibody HJ8.5 significantly decreases insoluble tau, decreases brain atrophy, and improves motor/sensorimotor function in a mouse model of tauopathy. These data further support the idea that anti-tau antibodies should be further assessed as a potential treatment for tauopathies.

Yanamandra, Kiran; Jiang, Hong; Mahan, Thomas E; Maloney, Susan E; Wozniak, David F; Diamond, Marc I; Holtzman, David M

2015-01-01

197

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

PubMed

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

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

2015-02-01

198

Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury  

PubMed Central

OBJECTIVE Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3–immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3–immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuro-protective endocannabinoid, in the injured brain. CONCLUSION These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials. PMID:15730585

Gopez, Jonas J.; Yue, Hongfei; Vasudevan, Ram; Malik, Amir S.; Fogelsanger, Lester N.; Lewis, Shawn; Panikashvili, David; Shohami, Esther; Jansen, Susan A.; Narayan, Raj K.; Strauss, Kenneth I.

2006-01-01

199

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain.  

PubMed

The present study was aimed to explore the potential of an antidepressant drug lithium (Li) in reducing aluminium (Al) induced neurotoxicity. To carry out the investigations, Al was administered orally (100 mg AlCl(3)/Kg b wt/day) whereas, Li was administered through diet (1.1 g Li(2)CO(3)/Kg diet, daily) for a total duration of 2 months. Al treatment resulted in a significant increase in the activity of enzyme nitric oxide synthase and the levels of L-citrulline which, however, were decreased appreciably following lithium supplementation. Al treatment also revealed an increase in DNA fragmentation as evidenced by an increase in number of comets. Interestingly, Li supplementation to Al treated rats reduced the damage inflicted on DNA by Al. Ultrastructural studies revealed an increase in chromatin condensation with discontinuity in nuclear membrane in both the cerebrum and cerebellum of Al treated rats which showed improvement following Li supplementation. Alterations in the structure of synapse and mitochondrial swelling were also seen. The present study shows the potential of Li in containing the damage inflicted by Al on rat brain. PMID:19936942

Bhalla, Punita; Singla, Neha; Dhawan, D K

2010-04-01

200

Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats  

PubMed Central

Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases. PMID:20859292

Taguchi, Akihiko; Zhu, Pengxiang; Cao, Fang; Kikuchi-Taura, Akie; Kasahara, Yukiko; Stern, David M; Soma, Toshihiro; Matsuyama, Tomohiro; Hata, Ryuji

2011-01-01

201

Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage.  

PubMed

Germinal matrix hemorrhage (GMH) is the most important adverse neurologic event during the newborn period. Evidence has shown that neonates with GMH and hydrocephalus have more severe damage compared to those with GMH alone. Our preliminary study demonstrated the role of iron in hydrocephalus and brain damage in adult rats following intraventricular hemorrhage. Therefore, the aim of the current study was to investigate iron accumulation and iron-handling proteins in a rat model of GMH and whether minocycline reduces iron overload after GMH and iron-induced brain injury in vivo. This study was divided into two parts. In the first part, rats received either a needle insertion or an intracerebral injection of 0.3 U of clostridial collagenase VII-S. Brain iron and brain iron handling proteins (heme oxygenase-1 and ferritin) were measured. In the second part, rats with a GMH were treated with minocycline or vehicle. Brain edema, brain cell death, hydrocephalus, iron-handling proteins and long-term motor function were examined. The result showed iron accumulation and upregulation of iron-handling proteins after GMH. Minocycline treatment significantly reduced GMH-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH. In conclusion, the current study found that iron plays a role in brain injury following GMH and that minocycline reduces iron overload after GMH and iron-induced brain injury. PMID:25451129

Guo, Jing; Chen, Qianwei; Tang, Jun; Zhang, Jianbo; Tao, Yihao; Li, Lin; Zhu, Gang; Feng, Hua; Chen, Zhi

2015-01-12

202

COG1410 Improves Cognitive Performance and Reduces Cortical Neuronal Loss in the Traumatically Injured Brain  

PubMed Central

Abstract We have previously shown that a single dose of COG1410, a small molecule ApoE-mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region, improves sensorimotor and motor outcome following cortical contusion injury (CCI). The present study evaluated a regimen of COG1410 following frontal CCI in order to examine its preclinical efficacy on cognitive recovery. Animals were prepared with a bilateral CCI of the frontal cortex. A regimen of COG1410 (0.8?mg/kg intravenously [IV]) was administered twice, at 30?min and again at 24?h post-CCI. Starting on day 11, the animals were tested for their acquisition of a reference memory task in the Morris water maze (MWM), followed by a working memory task in the MWM on day 15. Following CCI, the animals were also tested on the bilateral tactile adhesive removal test to measure sensorimotor dysfunction. On all of the behavioral tests the COG1410 group was no different from the uninjured sham group. Administration of the regimen of COG1410 significantly improved recovery on the reference and working memory tests, as well as on the sensorimotor test. Lesion analysis revealed that COG1410 significantly reduced the size of the injury cavity. Administration of COG1410 also reduced the number of degenerating neurons, as measured by Fluoro-Jade C staining, in the frontal cortex at 48?h post-CCI. These results suggest that a regimen of COG1410 appeared to block the development of significant behavioral deficits and reduced tissue loss. These combined findings suggest that COG1410 appears to have strong preclinical efficacy when administered following traumatic brain injury (TBI). PMID:19119914

Kaufman, Nicholas; Vitek, Michael P.; McKenna, Suzanne E.

2009-01-01

203

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

PubMed Central

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?reduced interleukin-1? (IL-1?) at all time points (p?reduces total and penumbral lesion volumes (at 24 and 48?hr), potentially by decreasing IL-1? without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72?hr post-HII when IL-1? levels remained low suggests that after rewarming, mechanisms unrelated to IL-1? 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. PMID:25424430

Yuan, Xiangpeng; Ghosh, Nirmalya; McFadden, Brian; Tone, Beatriz; Bellinger, Denise L.; Obenaus, Andre

2014-01-01

204

The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.  

PubMed

Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia. PMID:25446452

Song, Juhyun; Cheon, So Yeong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-01-21

205

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

PubMed

We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca2+ accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 ?M) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca2+ accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat acute ischemic stroke. PMID:24953828

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

2014-10-01

206

Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain  

PubMed Central

Objective: HIV-associated neurocognitive deficits remain a challenge despite suppressive combined antiretroviral therapy. Given the association between HIV-induced central nervous system (CNS) disease and replication of HIV in immune-activated macrophages, CCR5 antagonists may attenuate CNS disease by modulating inflammatory signaling and by limiting viral replication. Design: To establish whether initiating CCR5 inhibition during early infection altered CNS disease progression, outcomes were compared between simian immunodeficiency virus (SIV)-infected macaques treated with maraviroc (MVC) versus untreated SIV-infected macaques. Methods: Six SIV-infected rhesus macaques were treated with MVC monotherapy for 5 months beginning 24 days postinoculation; 22 SIV-infected animals served as untreated controls. SIV RNA levels in plasma, cerobrospinal fluid, and brain, and CNS expression of TNF? and CCL2 were measured by qRT-PCR. Immunostaining for CD68 and amyloid precursor protein in the brain was measured by image analysis. Plasma sCD163 was measured by ELISA. Results: SIV RNA and proviral DNA levels in brain were markedly lower with MVC treatment, demonstrating CCR5 inhibition reduces CNS replication of SIV and may reduce the CNS latent viral reservoir. MVC treatment also lowered monocyte and macrophage activation, represented by CNS CD68 immunostaining and plasma sCD163 levels, and reduced both TNF? and CCL2 RNA expression in brain. Treatment also reduced axonal amyloid precursor protein immunostaining to levels present in uninfected animals, consistent with neuroprotection. Conclusion: CCR5 inhibitors may prevent neurologic disorders in HIV-infected individuals by reducing inflammation and by limiting viral replication in the brain. Furthermore, CCR5 inhibitors may reduce the latent viral reservoir in the CNS. Adding CCR5 inhibitors to combined antiretroviral regimens may offer multiple neuroprotective benefits. PMID:24051706

Kelly, Kathleen M.; Beck, Sarah E.; Pate, Kelly A. Metcalf; Queen, Suzanne E.; Dorsey, Jamie L.; Adams, Robert J.; Avery, Lindsay B.; Hubbard, Walter; Tarwater, Patrick M.; Mankowski, Joseph L.

2013-01-01

207

Neuronal K(ATP) channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic-ischemic brain injury.  

PubMed

Neonatal hypoxic-ischemic brain injury and its related illness hypoxic-ischemic encephalopathy (HIE) are major causes of nervous system damage and neurological morbidity in children. Hypoxic preconditioning (HPC) is known to be neuroprotective in cerebral ischemic brain injury. K(ATP) channels are involved in ischemic preconditioning in the heart; however the involvement of neuronal K(ATP) channels in HPC in the brain has not been fully investigated. In this study, we investigated the role of HPC in hypoxia-ischemia (HI)-induced brain injury in postnatal seven-day-old (P7) CD1 mouse pups. Specifically, TTC (2,3,5-triphenyltetrazolium chloride) staining was used to assess the infarct volume, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling) to detect apoptotic cells, Western blots to evaluate protein level, and patch-clamp recordings to measure K(ATP) channel current activities. Behavioral tests were performed to assess the functional recovery after hypoxic-ischemic insults. We found that hypoxic preconditioning reduced infarct volume, decreased the number of TUNEL-positive cells, and improved neurobehavioral functional recovery in neonatal mice following hypoxic-ischemic insults. Pre-treatment with a K(ATP) channel blocker, tolbutamide, inhibited hypoxic preconditioning-induced neuroprotection and augmented neurodegeneration following hypoxic-ischemic injury. Pre-treatment with a K(ATP) channel opener, diazoxide, reduced infarct volume and mimicked hypoxic preconditioning-induced neuroprotection. Hypoxic preconditioning induced upregulation of the protein level of the Kir6.2 isoform and enhanced current activities of K(ATP) channels. Hypoxic preconditioning restored the HI-reduced PKC and pAkt levels, and reduced caspase-3 level, while tolbutamide inhibited the effects of hypoxic preconditioning. We conclude that K(ATP) channels are involved in hypoxic preconditioning-induced neuroprotection in neonatal hypoxic-ischemic brain injury. K(ATP) channel openers may therefore have therapeutic effects in neonatal hypoxic-ischemic brain injury. PMID:25448006

Sun, Hong-Shuo; Xu, Baofeng; Chen, Wenliang; Xiao, Aijiao; Turlova, Ekaterina; Alibraham, Ammar; Barszczyk, Andrew; Bae, Christine Y J; Quan, Yi; Liu, Baosong; Pei, Lin; Sun, Christopher L F; Deurloo, Marielle; Feng, Zhong-Ping

2015-01-01

208

Treatment with Ginsenoside Rb1, A Component of Panax Ginseng , Provides Neuroprotection in Rats Subjected to Subarachnoid Hemorrhage-Induced Brain Injury  

Microsoft Academic Search

\\u000a \\u000a Objective: Recent trials have shown Ginsenoside Rb1 (GRb1), an active component of a well known Chinese medicine Panax Ginseng, plays a significant role in improving the complications seen after an ischemic brain event. In the present study, we investigated\\u000a the use of GRb1 as a treatment modality to reduce brain edema, reduce arterial vasospasm, and improve neurobehavioral function\\u000a after subarachnoid

Yingbo Li; Jiping Tang; Nikan H. Khatibi; Mei Zhu; Di Chen; Liu Tu; Li Chen; Shali Wang

209

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I  

Microsoft Academic Search

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood–brain barrier on enzyme distribution. To circumvent

E. Kakkis; M. McEntee; C. Vogler; S. Le; B. Levy; P. Belichenko; W. Mobley; P. Dickson; S. Hanson; M. Passage

2004-01-01

210

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

PubMed Central

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

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

2010-01-01

211

Association of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain Infarction  

PubMed Central

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099

Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

2015-01-01

212

Medical prophylaxis and treatment of cystoid macular edema after cataract surgery  

Microsoft Academic Search

ObjectiveThe study aimed to determine the effectiveness of prophylactic medical intervention in reducing the incidence of cystoid macular edema (CME) and the effectiveness of medical treatment for chronic CME after cataract surgery.

Luca Rossetti; Jayanta Chaudhuri; Kay Dickersin

1998-01-01

213

The inhibitory effect of kakkonto, Japanese traditional (kampo) medicine, on brain penetration of oseltamivir carboxylate in mice with reduced blood-brain barrier function.  

PubMed

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

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

2015-01-01

214

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

PubMed Central

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

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

2015-01-01

215

NADPH Oxidase Inhibition Improves Neurological Outcomes in Surgically-Induced Brain Injury  

PubMed Central

Neurosurgical procedures can result in brain injury by various means including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause post-operative complications such as brain edema. By creating a mouse model of SBI, we tested whether NADPH oxidase, an important reactive oxygen species producing enzyme, is involved in SBI using transgenic mice lacking gp91phox subunit of NADPH oxidase (gp91phox KO) and apocynin, a specific inhibitor of NADPH oxidase. Neurological function and brain edema were evaluated at 24 hours post-SBI in gp91phox KO and wild-type littermates grouped into SBI and sham-surgery groups. Alternatively, mice were grouped into vehicle- and apocynin-treated (5mg/kg, i.p. 30 minutes before SBI) groups. Oxidative stress indicated by lipid peroxidation (LPO) was measured at 3 and 24 hours post SBI. The gp91phox KO mice, but not the apocynin-treated mice showed significantly improved neurological scores. Brain edema was observed in both gp91phox KO and wild-type groups after SBI; however, there was no significant difference between these two groups. Brain edema was also not affected by apocynin-pretreatment. LPO levels were significantly higher in SBI group in both gp91phox KO and wild-type groups as compared to sham group. A trend, although without statistical significance, was noted towards attenuation of LPO in the gp91phox KO animals as compared to wild-type group. LPO levels were significantly attenuated at 3 hours post-SBI by apocynin pretreatment but not at 24 hours post-SBI. These results suggest that chronic and acute inhibition of NADPH oxidase activity does not reduce brain edema after SBI. Long-term inhibition of NADPH oxidase, however improves neurological functions after SBI. PMID:17317004

Lo, Wendy; Bravo, Thomas; Jadhav, Vikram; Zhang, John H.; Tang, Jiping

2007-01-01

216

NADPH oxidase inhibition improves neurological outcomes in surgically-induced brain injury.  

PubMed

Neurosurgical procedures can result in brain injury by various means including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause post-operative complications such as brain edema. By creating a mouse model of SBI, we tested whether NADPH oxidase, an important reactive oxygen species producing enzyme, is involved in SBI using transgenic mice lacking gp91phox subunit of NADPH oxidase (gp91phox KO) and apocynin, a specific inhibitor of NADPH oxidase. Neurological function and brain edema were evaluated at 24 h post-SBI in gp91phox KO and wild-type littermates grouped into SBI and sham-surgery groups. Alternatively, mice were grouped into vehicle- and apocynin-treated (5 mg/kg, i.p. 30 min before SBI) groups. Oxidative stress indicated by lipid peroxidation (LPO) was measured at 3 and 24 h post-SBI. The gp91phox KO mice, but not the apocynin-treated mice showed significantly improved neurological scores. Brain edema was observed in both gp91phox KO and wild-type groups after SBI; however, there was no significant difference between these two groups. Brain edema was also not affected by apocynin-pretreatment. LPO levels were significantly higher in SBI group in both gp91phox KO and wild-type groups as compared to sham group. A trend, although without statistical significance, was noted towards attenuation of LPO in the gp91phox KO animals as compared to wild-type group. LPO levels were significantly attenuated at 3 h post-SBI by apocynin-pretreatment but not at 24 h post-SBI. These results suggest that chronic and acute inhibition of NADPH oxidase activity does not reduce brain edema after SBI. Long-term inhibition of NADPH oxidase, however improves neurological functions after SBI. PMID:17317004

Lo, Wendy; Bravo, Thomas; Jadhav, Vikram; Titova, Elena; Zhang, John H; Tang, Jiping

2007-03-13

217

Reexpansion pulmonary edema in children  

PubMed Central

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

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

2013-01-01

218

Progesterone protects blood-brain barrier function and improves neurological outcome following traumatic brain injury in rats  

PubMed Central

Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction and neurological deficits following traumatic brain injury (TBI). The aim of the present study was to investigate the effects of progesterone on the expression of the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nuclear factor ?B (NF-?B) and tumor necrosis factor-? (TNF-?) in the brain, BBB permeability, cerebral edema and neurological outcome, as well as to explore the mechanism of its neuroprotective effect. In this study, male rats were randomly divided into three groups: a sham-operated group (SHAM), a TBI group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was established using a modified Feeney’s weight-dropping method. Brain samples were extracted 24 h following injury. The expression levels of COX-2 and NF-?B were examined using immunohistochemistry, whilst the expression levels of PGE2 and TNF-? were detected by enzyme-linked immunosorbent assay. BBB permeability was analyzed using Evans blue and cerebral edema was determined using the dry-wet method. The neurological outcome was evaluated using the modified neurological severity score test. The results revealed that progesterone treatment significantly reduced post-injury inflammatory response, brain edema and Evans blue dye extravasation, and improved neurological scores compared with those in the TBI group. In conclusion, the inhibition of inflammation may be an important mechanism by which progesterone protects the BBB and improves neurological outcome. PMID:25120639

SI, DAOWEN; LI, JUAN; LIU, JIANG; WANG, XIAOYIN; WEI, ZIFENG; TIAN, QINGYOU; WANG, HAITAO; LIU, GANG

2014-01-01

219

Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.  

PubMed

The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish. PMID:24858302

Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

2014-09-01

220

Conjugated deferoxamine reduces blood-brain barrier disruption in experimental optic neuritis.  

PubMed

The purpose of this paper was to investigate the role of deferoxamine (DFO) scavenging of hydroxyl radical (.OH) on disruption of the blood-brain barrier (BBB) and demyelination in experimental optic neuritis. Eighteen strain-13 guinea pigs were sensitized for experimental allergic encephalomyelitis. Nine animals received 100 mg/kg of hydroxyethyl starch-conjugated (HES) DFO by daily intraperitoneal injection commencing the day of antigenic sensitization. Nine paired litter mates received daily IP injections of HES. Serial fat-suppressed magnetic resonance imaging of the optic nerves was obtained with a T2 weighting (T2w) to evaluate demyelination and after intravascular administration of Gd-DTPA to evaluate BBB disruption. The intensity of Gd-DTPA enhancement and T2w signal of the optic nerves was quantitated 3, 7, 10 and 14 days after antigenic sensitization. Animals were then sacrificed and the optic nerves processed for light and transmission electron microscopy with ultracytochemical localization of endogenous hydrogen peroxide (H2O2) and immunogold colocalization of extravasated serum albumin. The area of the optic nerve head, intensity of toluidine blue staining, and the cellular infiltrate were digitized and quantitated. Administration of HES-DFO significantly reduced the intensity of Gd-DTPA enhancement in the optic nerves of HES-DFO-treated animals compared to paired control HES animals (p = 0.0236), with the mean difference between control and treated animals of 19.39. The difference in T2w signal was not significant (p = 0.39), with a mean difference between control and treated animals of -5.51. The intensity of toluidine blue staining of optic nerve specimens was slightly less with HES-DFO compared to untreated animals (mean pair difference 2.48), and the inflammatory infiltrate was reduced with HES-DFO compared to untreated animals (mean pair difference = 61.57); these differences were not statistically significant. In the optic nerve specimens of both groups cerium perhydroxide-derived H2O2 reaction product was evident in a predominantly perivascular and perineural distribution. Immunogold-labeled serum albumin showed extravasation at foci of perivascular inflammation in both the presence and absence of H2O2-derived reaction product. Conjugated DFO reduces disruption of the BBB, as measured by Gd-DTPA enhancement, suggesting the .OH radical generated from perivascular H2O2 may play a role in alterations of vascular permeability in experimental optic neuritis. PMID:7533278

Guy, J; McGorray, S; Qi, X; Fitzsimmons, J; Mancuso, A; Rao, N

1994-01-01

221

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain[S  

PubMed Central

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID:22058426

Larsen, Scott D.; Wilson, Michael W.; Abe, Akira; Shu, Liming; George, Christopher H.; Kirchhoff, Paul; Showalter, H. D. Hollis; Xiang, Jianming; Keep, Richard F.; Shayman, James A.

2012-01-01

222

Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation  

PubMed Central

Deep brain stimulation (DBS) provides dramatic tremor relief when delivered at high-stimulation frequencies (more than ?100 Hz), but its mechanisms of action are not well-understood. Previous studies indicate that high-frequency stimulation is less effective when the stimulation train is temporally irregular. The purpose of this study was to determine the specific characteristics of temporally irregular stimulus trains that reduce their effectiveness: long pauses, bursts, or irregularity per se. We isolated these characteristics in stimulus trains and conducted intraoperative measurements of postural tremor in eight volunteers. Tremor varied significantly across stimulus conditions (P < 0.015), and stimulus trains with pauses were significantly less effective than stimulus trains without (P < 0.002). There were no significant differences in tremor between trains with or without bursts or between trains that were irregular or periodic. Thus the decreased effectiveness of temporally irregular DBS trains is due to long pauses in the stimulus trains, not the degree of temporal irregularity alone. We also conducted computer simulations of neuronal responses to the experimental stimulus trains using a biophysical model of the thalamic network. Trains that suppressed tremor in volunteers also suppressed fluctuations in thalamic transmembrane potential at the frequency associated with cerebellar burst-driver inputs. Clinical and computational findings indicate that DBS suppresses tremor by masking burst-driver inputs to the thalamus and that pauses in stimulation prevent such masking. Although stimulation of other anatomic targets may provide tremor suppression, we propose that the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus. PMID:21994263

Birdno, Merrill J.; Kuncel, Alexis M.; Dorval, Alan D.; Turner, Dennis A.; Gross, Robert E.

2012-01-01

223

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

PubMed Central

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

Bemis, J C; Seegal, R F

1999-01-01

224

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

PubMed Central

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

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

2013-01-01

225

Reduced serum brain-derived neurotrophic factor in patients with first onset vitiligo  

PubMed Central

Purpose Vitiligo is an acquired pigmentary skin disease that can cause serious cosmetic problems. There have been numerous and well established studies that have demonstrated the comorbidity of various psychiatric disorders in patients with vitiligo. However, to our knowledge, there have been no studies investigating whether a psychiatric biomarker, such as brain-derived neurotrophic factor (BDNF), is associated with vitiligo. Patients and methods This study was conducted in Nam?k Kemal University Medical Faculty, Departments of Dermatology and Psychiatry between January 2013 and September 2014. After meeting inclusion and exclusion criteria, serum BDNF levels were assayed in 57 patients with first onset vitiligo and no known current or past psychiatric disorder and compared with BDNF levels in 58 age and sex matched healthy subjects. Results The age and female/male ratios were similar between groups. The mean values of serum BDNF were 1.57±0.97 ng/dL and 2.37±1.73 ng/dL in the vitiligo group and in the healthy control group, respectively. The mean BDNF level was significantly higher in the healthy control group compared with the vitiligo group (t=2.76, P=0.007). Conclusion This is the first study to compare serum BDNF levels between patients with vitiligo and healthy subjects. The reduced level of serum BDNF in patients with vitiligo may be directly related to the etiology of vitiligo or associated with the high percentage of psychiatric disorders in that patient population. Further studies are needed to support our preliminary results. PMID:25540586

Yanik, M Emin; Erfan, Gamze; Albayrak, Yakup; Aydin, Murat; Kulac, Mustafa; Kuloglu, Murat

2014-01-01

226

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

PubMed

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

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

2013-10-16

227

Calcified neurocysticercus, perilesional edema, and histologic inflammation.  

PubMed

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

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

2014-02-01

228

Modern Management of Cardiogenic Pulmonary Edema  

Microsoft Academic Search

Cardiogenic pulmonary edema (CPE) is a common and potentially deadly condition frequently encountered in emergency medicine. Many conditions exist that directly or indirectly lead to the development of pulmonary edema. Regardless of the underlying cause of CPE, all patients who develop CPE must be diagnosed and managed expeditiously. Patients who have developed CPE can quickly develop respiratory failure if delays

Amal Mattu; Joseph P. Martinez; Brian S. Kelly

2005-01-01

229

Acute pulmonary edema following carbon monoxide poisoning  

Microsoft Academic Search

This report describes a patient who presented with coma and acute pulmonary edema after severe carbon monoxide poisoning. Hemodynamic evaluation revealed elevated systemic and pulmonary arterial, pulmonary wedge and right atrial pressures, together with an increased cardiac output. These findings are compatible with the hypothesis that a neurogenic mechanism plays a role in the pulmonary edema of carbon monoxide poisoning.

R. Naeije; A. Peretz; A. Cornil

1980-01-01

230

Effect of Pulmonary Edema on Tracheal Diameter  

Microsoft Academic Search

Background: Though it is well known that cardiogenic and noncardiogenic pulmonary edema can cause changes in lung mechanics, actual alterations in tracheal diameter have not been described. Objective: To evaluate the effects of pulmonary edema induced by increased left atrial pressure (cardiogenic) and Perilla ketone (PK; noncardiogenic) on tracheal diameter in chronically instrumented awake sheep. Methods: We investigated the effects

James R. Snapper; D. Scott Trochtenberg; Young S. Hwang; Peter L. Lefferts; Frank E. Carroll; John A. Worrell; Dennis M. O’Donnell

1999-01-01

231

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

PubMed Central

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

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

2011-01-01

232

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

PubMed

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

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

2015-01-01

233

Mild Hypothermia Reduces Tissue Plasminogen Activator-Related Hemorrhage and Blood Brain Barrier Disruption After Experimental Stroke  

PubMed Central

Therapeutic hypothermia has shown neuroprotective promise, but whether it can be used to improve outcome in stroke has yet to be determined in patients. Recombinant tissue plasminogen activator (rt-PA) is only given to a minority of patients with acute ischemic stroke, and is not without risk, namely significant brain hemorrhage. We explored whether mild hypothermia, in combination with rt-PA, influences the safety of rt-PA. Mice were subjected to middle cerebral artery occlusion (MCAO) using a filament model, followed by 24 hours reperfusion. Two paradigms were studied. In the first paradigm, cooling and rt-PA treatment began at the same time upon reperfusion, whereas in the second paradigm, cooling began soon after ischemia onset, and rt-PA began after re-warming and upon reperfusion. Experimental groups included: tPA treatment at normothermia (37°C), rt-PA treatment at hypothermia (33°C), no rt-PA at normothermia, and no rt-PA treatment at hypothermia. Infarct size, neurological deficit scores, blood brain barrier (BBB) permeability, brain hemorrhage, and expression of endogenous tissue plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor (PAI-1) were assessed. For both paradigms, hypothermia reduced infarct size and neurological deficits compared to normothermia, regardless of whether rt-PA was given. rt-PA treatment increased brain hemorrhage and BBB disruption compared to normothermia, and this was prevented by cooling. However, mortality was higher when rt-PA and cooling were administered at the same time, beginning 1–2 hours post MCAO. Endogenous tPA expression was reduced in hypothermic mice, whereas PAI-1 levels were unchanged by cooling. In the setting of rt-PA treatment, hypothermia reduces brain hemorrhage, and BBB disruption, suggesting that combination therapy with mild hypothermia and rt-PA appears safe. PMID:23781399

Tang, Xian Nan; Liu, Liping; Koike, Maya A.

2013-01-01

234

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

EPA Science Inventory

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

235

N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis  

Microsoft Academic Search

GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid b-galactosidase (b-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired

Julie L. Kasperzyk; Mohga M. El-Abbadi; Eric C. Hauser; Alessandra d'Azzo; Frances M. Platt; Thomas N. Seyfried

2004-01-01

236

Brain-Derived Neurotrophic Factor Reduces Blood Glucose Level in Obese Diabetic Mice but Not in Normal Mice  

Microsoft Academic Search

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. However, it is not yet known if BDNF works on the endocrine system itself. Here we report that BDNF improves hyperglycemia in obese diabetic animals. BDNF reduced the blood glucose level in obesedb\\/dbdiabetic mice in which the effect of BDNF was age-dependent and high under the condition of hyperinsulinemia,

Michiko Ono; Junji Ichihara; Takeshi Nonomura; Yasushi Itakura; Mutsuo Taiji; Chikao Nakayama; Hiroshi Noguchi

1997-01-01

237

Ethyl docosahexaenoic acid administration during intrauterine life enhances prostanoid production and reduces free radicals generation in the fetal rat brain  

Microsoft Academic Search

Recently we demonstrated that a single intra-amniotic injection of ethyl (Et) docosahexaenoic acid (Et-DHA, 22:6n-3) reduced by 39% the ability of fetal brain slices to form Fe 2+mediated lipid peroxides (LPO) measured by thiobarbituric acid reactants (TBAR), suggesting an antioxidant role for DHA (1). Under these conditions, arachidonic acid (AA) was preferentially lost from major phospholipids, suggesting a relatively greater

Sabina Glozman; Pnina Green; Batia Kamensky; Lev Weiner; Ephraim Yavin

1999-01-01

238

Single Administration of Tripeptide ?-MSH(11–13) Attenuates Brain Damage by Reduced Inflammation and Apoptosis after Experimental Traumatic Brain Injury in Mice  

PubMed Central

Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (?-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of ?-MSH, the C-terminal tripeptide ?-MSH(11–13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of ?-MSH(11–13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg ?-MSH(11–13) or 0.9% NaCl) showed a considerable smaller trauma in ?-MSH(11–13) injected mice. The expression of the inflammatory markers TNF-? and IL-1? as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single ?-MSH(11–13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury. PMID:23940690

Schaible, Eva-Verena; Steinsträßer, Arne; Jahn-Eimermacher, Antje; Luh, Clara; Sebastiani, Anne; Kornes, Frida; Pieter, Dana; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

2013-01-01

239

Single administration of tripeptide ?-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice.  

PubMed

Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (?-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of ?-MSH, the C-terminal tripeptide ?-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels increased over time with a 3-fold maximum at 12 h compared to naive brain tissue. The effect of ?-MSH(11-13) on secondary lesion volume determined in cresyl violet stained sections (intraperitoneal injection 30 min after insult of 1 mg/kg ?-MSH(11-13) or 0.9% NaCl) showed a considerable smaller trauma in ?-MSH(11-13) injected mice. The expression of the inflammatory markers TNF-? and IL-1? as well as the total amount of Iba-1 positive cells were not reduced. However, cell branch counting of Iba-1 positive cells revealed a reduced activation of microglia. Furthermore, tripeptide injection reduced neuronal apoptosis analyzed by cleaved caspase-3 and NeuN staining. Based on the results single ?-MSH(11-13) administration offers a promising neuroprotective property by modulation of inflammation and prevention of apoptosis after traumatic brain injury. PMID:23940690

Schaible, Eva-Verena; Steinsträßer, Arne; Jahn-Eimermacher, Antje; Luh, Clara; Sebastiani, Anne; Kornes, Frida; Pieter, Dana; Schäfer, Michael K; Engelhard, Kristin; Thal, Serge C

2013-01-01

240

Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer's disease.  

PubMed

Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease. PMID:24332448

Huang, Xiao-Tian; Qian, Zhong-Ming; He, Xuan; Gong, Qi; Wu, Ka-Chun; Jiang, Li-Rong; Lu, Li-Na; Zhu, Zhou-Jing; Zhang, Hai-Yan; Yung, Wing-Ho; Ke, Ya

2014-05-01

241

Effect of radical scavengers and hyperbaric oxygen on smoke-induced pulmonary edema.  

PubMed

Respiratory complications, especially pulmonary edema, account for over 50% of mortalities in inhalation injuries. This study was conducted to determine the effect of free radical scavengers and hyperbaric oxygen (HBO) in vivo on reducing pulmonary edema. Adult New Zealand rabbits were allowed to breath cooled, cotton smoke until a significant inhalation lung injury was produced. Five percent of body weight lactated Ringer's solution was then administered i.v. over 2 h. The following free radical scavengers were given as bolus infusions at the beginning of fluids resuscitation: superoxide dismutase, catalase, butylated hydroxytoluene/piperonyl butoxide, and mannitol. At the completion of fluid administration, half of the subjects were given HBO treatment. Pulmonary edema was then measured as extravascular lung water and wet/dry lung weight. Results indicate that free radical scavengers or HBO reduce pulmonary edema. Free radical scavengers in conjunction with HBO showed no significant improvement over HBO or free radical scavengers alone. PMID:8180564

Stewart, R J; Mason, S W; Taira, M T; Hasson, G E; Naito, M S; Yamaguchi, K T

1994-03-01

242

Adaptive decreases in amino acids (taurine in particular), creatine, and electrolytes prevent cerebral edema in chronically hyponatremic mice: Rapid correction (experimental model of central pontine myelinolysis) causes dehydration and shrinkage of brain  

Microsoft Academic Search

The experimental model of central pontine myelinolysis—chronic (4-day) hyponatremia induced by daily injections of hypotonic dextrose solutions and vasopressin followed by rapid correction with saline—was used in young fasted and thirsted mice. In normal controls, chronic fasting and thirsting lowered plasma and brain glucose levels and cerebral glycolytic and tricarboxylic acid cycle metabolic fluxes. The fasting state had little effect

Jean Holowach Thurston; Richard E. Hauhart; James S. Nelson

1987-01-01

243

Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease  

PubMed Central

It has been established for a long time that brain glucose metabolism is impaired in Alzheimer's disease. Recent studies have demonstrated that impaired brain glucose metabolism precedes the appearance of clinical symptoms, implying its active role in the development of Alzheimer's disease. However, the molecular mechanism by which this impairment contributes to the disease is not known. In this study, we demonstrated that protein O-GlcNAcylation, a common post-translational modification of nucleocytoplasmic proteins with ?-N-acetyl-glucosamine and a process regulated by glucose metabolism, was markedly decreased in Alzheimer's disease cerebrum. More importantly, the decrease in O-GlcNAc correlated negatively with phosphorylation at most phosphorylation sites of tau protein, which is known to play a crucial role in the neurofibrillary degeneration of Alzheimer's disease. We also found that hyperphosphorylated tau contained 4-fold less O-GlcNAc than non-hyperphosphorylated tau, demonstrating for the first time an inverse relationship between O-GlcNAcylation and phosphorylation of tau in the human brain. Downregulation of O-GlcNAcylation by knockdown of O-GlcNAc transferase with small hairpin RNA led to increased phosphorylation of tau in HEK-293 cells. Inhibition of the hexosamine biosynthesis pathway in rat brain resulted in decreased O-GlcNAcylation and increased phosphorylation of tau, which resembled changes of O-GlcNAcylation and phosphorylation of tau in rodent brains with decreased glucose metabolism induced by fasting, but not those in rat brains when protein phosphatase 2A was inhibited. Comparison of tau phosphorylation patterns under various conditions suggests that abnormal tau hyperphosphorylation in Alzheimer's disease brain may result from downregulation of both O-GlcNAcylation and protein phosphatase 2A. These findings suggest that impaired brain glucose metabolism leads to abnormal hyperphosphorylation of tau and neurofibrillary degeneration via downregulation of tau O-GlcNAcylation in Alzheimer's disease. Thus, restoration of brain tau O-GlcNAcylation and protein phosphatase 2A activity may offer promising therapeutic targets for treating Alzheimer's disease. PMID:19451179

Liu, Fei; Shi, Jianhua; Tanimukai, Hitoshi; Gu, Jinhua; Gu, Jianlan; Grundke-Iqbal, Inge; Iqbal, Khalid

2009-01-01

244

[Volumetric verification of edema protection with Serrapeptase after third molar osteotomy].  

PubMed

Preventive edema protection using Serrapeptase after standardized one-stage osteotomy procedures of 4 third molars was verified by means of an opto-electronic measuring instrument. This measuring technique proved to be a sensitive tool for demonstrating the efficacy of Serrapeptase in reducing postoperative edema. Although statistically significant, the reduction of soft tissue swelling was only approximately 15% when compared with a patient group without Serrapeptase medication. PMID:1816962

Merten, H A; Müller, K; Drubel, F; Halling, F

1991-01-01

245

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

PubMed Central

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

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

2012-01-01

246

The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer’s disease  

PubMed Central

Background The pathological features of the common neurodegenerative conditions, Alzheimer’s disease (AD), Parkinson’s disease and multiple sclerosis are all known to be associated with iron dysregulation in regions of the brain where the specific pathology is most highly expressed. Iron accumulates in cortical plaques and neurofibrillary tangles in AD where it participates in redox cycling and causes oxidative damage to neurons. To understand these abnormalities in the distribution of iron the expression of proteins that maintain systemic iron balance was investigated in human AD brains and in the APP-transgenic (APP-tg) mouse. Results Protein levels of hepcidin, the iron-homeostatic peptide, and ferroportin, the iron exporter, were significantly reduced in hippocampal lysates from AD brains. By histochemistry, hepcidin and ferroportin were widely distributed in the normal human brain and co-localised in neurons and astrocytes suggesting a role in regulating iron release. In AD brains, hepcidin expression was reduced and restricted to the neuropil, blood vessels and damaged neurons. In the APP-tg mouse immunoreactivity for ferritin light-chain, the iron storage isoform, was initially distributed throughout the brain and as the disease progressed accumulated in the core of amyloid plaques. In human and mouse tissues, extensive AD pathology with amyloid plaques and severe vascular damage with loss of pericytes and endothelial disruption was seen. In AD brains, hepcidin and ferroportin were associated with haem-positive granular deposits in the region of damaged blood vessels. Conclusion Our results suggest that the reduction in ferroportin levels are likely associated with cerebral ischaemia, inflammation, the loss of neurons due to the well-characterised protein misfolding, senile plaque formation and possibly the ageing process itself. The reasons for the reduction in hepcidin levels are less clear but future investigation could examine circulating levels of the peptide in AD and a possible reduction in the passage of hepcidin across damaged vascular endothelium. Imbalance in the levels and distribution of ferritin light-chain further indicate a failure to utilize and release iron by damaged and degenerating neurons. PMID:24252754

2013-01-01

247

Acute pulmonary edema associated with naphazoline ingestion.  

PubMed

In published reports of naphazoline ingestion, clinical effects are hypertension, bradycardia, pallor, diaphoresis, and respiratory distress. We report three cases of acute pulmonary edema after the intentional ingestion of naphazoline-containing antiseptic first aid liquid. These cases presented with altered mental status, hypertension, bradycardia, and diaphoresis. Chest x-ray on admission revealed acute pulmonary edema. Two cases required mechanical ventilation. All of these clinical effects resolved within 24 hours and the patients were discharged with no sequelae. Since naphazoline stimulates the peripheral alpha-2 adrenergic receptor, we speculate that intense vasoconstriction may have elevated cardiac afterload and left atrial-ventricular blood volume and caused acute pulmonary edema. PMID:17852165

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

2008-03-01

248

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

PubMed

When we observe someone perform a familiar action, we can usually predict what kind of sound that action will produce. Musical actions are over-experienced by musicians and not by non-musicians, and thus offer a unique way to examine how action expertise affects brain processes when the predictability of the produced sound is manipulated. We used functional magnetic resonance imaging to scan 11 drummers and 11 age- and gender-matched novices who made judgments on point-light drumming movements presented with sound. In Experiment 1, sound was synchronized or desynchronized with drumming strikes, while in Experiment 2 sound was always synchronized, but the natural covariation between sound intensity and velocity of the drumming strike was maintained or eliminated. Prior to MRI scanning, each participant completed psychophysical testing to identify personal levels of synchronous and asynchronous timing to be used in the two fMRI activation tasks. In both experiments, the drummers' brain activation was reduced in motor and action representation brain regions when sound matched the observed movements, and was similar to that of novices when sound was mismatched. This reduction in neural activity occurred bilaterally in the cerebellum and left parahippocampal gyrus in Experiment 1, and in the right inferior parietal lobule, inferior temporal gyrus, middle frontal gyrus and precentral gyrus in Experiment 2. Our results indicate that brain functions in action-sound representation areas are modulated by multimodal action expertise. PMID:21397699

Petrini, Karin; Pollick, Frank E; Dahl, Sofia; McAleer, Phil; McKay, Lawrie S; McKay, Lawrie; Rocchesso, Davide; Waadeland, Carl Haakon; Love, Scott; Avanzini, Federico; Puce, Aina

2011-06-01

249

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

PubMed

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

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

2015-01-01

250

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

251

MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome  

Microsoft Academic Search

Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, syndactyly and cardiac defect. We show here that heterozygous mutations in the gene MYCN are present in Feingold syndrome. All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain

Jacopo Celli; Jeroen van Reeuwijk; Tuula Rinne; Bob Glaudemans; Ellen van Beusekom; Paul Rieu; Ruth A Newbury-Ecob; Chin Chiang; Han G Brunner; Hans van Bokhoven

2005-01-01

252

Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels  

Microsoft Academic Search

Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or

S Chi; W Cai; P Liu; Z Zhang; X Chen; L Gao; J Qi; L Bi; L Chen; Z Qi

2010-01-01

253

Reduced N400 Semantic Priming Effects in Adult Survivors of Paediatric and Adolescent Traumatic Brain Injury  

ERIC Educational Resources Information Center

The immediate and long-term neural correlates of linguistic processing deficits reported following paediatric and adolescent traumatic brain injury (TBI) are poorly understood. Therefore, the current research investigated event-related potentials (ERPs) elicited during a semantic picture-word priming experiment in two groups of highly functioning…

Knuepffer, C.; Murdoch, B. E.; Lloyd, D.; Lewis, F. M.; Hinchliffe, F. J.

2012-01-01

254

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats  

SciTech Connect

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals.

Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr. (Univ. of Washington, Seattle (USA))

1990-05-01

255

Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation  

NASA Astrophysics Data System (ADS)

This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications.

Jeon, Myounggun; Cho, Jeiwon; Kim, Yun Kyung; Jung, Dahee; Yoon, Eui-Sung; Shin, Sehyun; Cho, Il-Joo

2014-02-01

256

Mechanisms of fluid accumulation in retinal edema  

Microsoft Academic Search

This paper reviews the anatomic and physiologic conditions which predispose to fluid accumulation within the retina. Retinal\\u000a edema has its inception in disease that causes a breakdown of the blood-retinal barrier in retinal capillaries and\\/or the\\u000a retinal pigment epithelium (RPE). Edema develops not only because protein and fluid enter the extracellular space, but because\\u000a the external limiting membrane and the

Michael F. Marmor

1999-01-01

257

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

PubMed Central

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

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

2015-01-01

258

Disruption of Ion Homeostasis in the Neurogliovascular Unit Underlies the Pathogenesis of Ischemic Cerebral Edema  

PubMed Central

Cerebral edema is a major cause of morbidity and mortality following ischemic stroke, but its underlying molecular pathophysiology is incompletely understood. Recent data have revealed the importance of ion flux via channels and transporters expressed in the neurogliovascular unit in the development of ischemia-triggered cytotoxic edema, vasogenic edema, and hemorrhagic conversion. Disruption of homeostatic mechanisms governing cell volume regulation and epithelial/endothelial ion transport due to ischemia-associated energy failure results in the thermodynamically driven re-equilibration of solutes and water across the CSF–blood and blood–brain barriers that ultimately increases the brain’s extravascular volume. Additionally, hypoxia, inflammation, and other stress-triggered increases in the functional expression of ion channels and transporters normally expressed at low levels in the neurogliovascular unit cause disruptions in ion homeostasis that contribute to ischemic cerebral edema. Here, we review the pathophysiological significance of several molecular mediators of ion transport expressed in the neurogliovascular unit, including targets of existing FDA-approved drugs, which might be potential nodes for therapeutic intervention. PMID:24323726

Khanna, Arjun; Kahle, Kristopher T.; Gerzanich, Volodymyr

2014-01-01

259

Neuronal expression of STM2 mRNA in human brain is reduced in Alzheimer's disease.  

PubMed

Mutations in the STM2 gene cause familial Alzheimer's disease (AD) in Volga Germans. To understand the function of this protein and how mutations lead to AD, it is important to determine which cell types in the brain express this gene. In situ hybridization histochemistry indicates that STM2 expression in the human brain is widespread and is primarily neuronal. In addition, STM2 mRNA is expressed in a cell line with neuronal origins. Quantification of the level of expression of the STM2 message in the basal forebrain, frontal cortex, and hippocampus reveals a significant decrease in AD-affected subjects compared to normal age-matched controls. These data suggest that downregulation of neuronal STM2 gene expression may be involved in the progression of AD. PMID:8918895

McMillan, P J; Leverenz, J B; Poorkaj, P; Schellenberg, G D; Dorsa, D M

1996-11-01

260

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

PubMed

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

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

2015-01-01

261

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

SciTech Connect

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

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

2011-03-01

262

Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine Abusers  

Microsoft Academic Search

ObjectiveGender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.MethodTo test this we compared brain metabolism (using PET and 18FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral

Nora D. Volkow; Dardo Tomasi; Gene-Jack Wang; Joanna S. Fowler; Frank Telang; Rita Z. Goldstein; Nelly Alia-Klein; Christopher Wong; Kenji Hashimoto

2011-01-01

263

Vascular risk and A? interact to reduce cortical thickness in AD vulnerable brain regions  

PubMed Central

Objective: The objective of this study was to define whether vascular risk factors interact with ?-amyloid (A?) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD). Methods: Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of A? was assessed using [11C]Pittsburgh compound B–PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index. Results: Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of A?. These frontotemporal regions are also affected in individuals with A? deposition, but the latter show additional thinning in parietal cortices. A? and vascular risk were found to interact in posterior (especially in parietal) brain regions, where A? has its greatest effect. In this way, the negative effect of A? in posterior regions is increased by the presence of vascular risk. Conclusion: A? and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD. PMID:24907234

Reed, Bruce R.; Madison, Cindee M.; Wirth, Miranka; Marchant, Natalie L.; Kriger, Stephen; Mack, Wendy J.; Sanossian, Nerses; DeCarli, Charles; Chui, Helena C.; Weiner, Michael W.; Jagust, William J.

2014-01-01

264

Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging  

PubMed Central

Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18–83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G × A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging. PMID:24191011

Glahn, David C.; Kent, Jack W.; Sprooten, Emma; Diego, Vincent P.; Winkler, Anderson M.; Curran, Joanne E.; McKay, D. Reese; Knowles, Emma E.; Carless, Melanie A; Göring, Harald H. H.; Dyer, Thomas D.; Olvera, Rene L.; Fox, Peter T.; Almasy, Laura; Charlesworth, Jac; Kochunov, Peter; Duggirala, Ravi; Blangero, John

2013-01-01

265

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

PubMed Central

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

Hakon, Jakob; Ruscher, Karsten; Tomasevic, Gregor

2015-01-01

266

Improving White Matter Tractography by Resolving the Challenges of Edema  

E-print Network

Improving White Matter Tractography by Resolving the Challenges of Edema Jérémy Lecoeur1 , Emmanuel a two-compartment model to the data and extracted measures of free water in edema as well as corrected in the presence of extensive edema. In addition, other peritumoral tracts in regions of edema were also tracked

Paris-Sud XI, Université de

267

Dural Arteriovenous Fistula of the Cavernous Sinus with Brainstem Edema  

Microsoft Academic Search

Dural arteriovenous fistula of the cavernous sinus is usually a benign disease and rarely has brainstem edema as its complication. We present a patient with dural arteriovenous fistula of the cavernous sinus and brainstem edema. The brainstem edema resolved after embolization. Embolization should be considered first whenever brainstem edema occurs, progressive visual deterioration or increased intracranial pressure is encountered in

MICHAEL MU; HUO TENG; JIING-FENG LIRNG; FENG-CHI CHANG; SHING-SU CHEN; CHAO-BAO LUO; CHENG-YEN CHANG; JEN-HUEY CHIANG

268

Low-power hardware implementation of movement decoding for brain computer interface with reduced-resolution discrete cosine transform.  

PubMed

This paper describes a low-power hardware implementation for movement decoding of brain computer interface. Our proposed hardware design is facilitated by two novel ideas: (i) an efficient feature extraction method based on reduced-resolution discrete cosine transform (DCT), and (ii) a new hardware architecture of dual look-up table to perform discrete cosine transform without explicit multiplication. The proposed hardware implementation has been validated for movement decoding of electrocorticography (ECoG) signal by using a Xilinx FPGA Zynq-7000 board. It achieves more than 56× energy reduction over a reference design using band-pass filters for feature extraction. PMID:25570284

Minho Won; Albalawi, Hassan; Xin Li; Thomas, Donald E

2014-08-01

269

The impact of dietary isoflavonoids on malignant brain tumors  

PubMed Central

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

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

2014-01-01

270

Edema facial en síndrome de vena cava superior Facial Edema in Superior Vena Cava Syndrome  

Microsoft Academic Search

Summary We report two cases of superior vena cava syndrome (SVCS). The first symptom was facial edema. The etiology of the first case was a thymic neuroendocrine carcinoma. The second case was caused by a central endovenous catheter for chemoterapy, inducing trombosis in the rigth jugular vein. We reviewed the etiology of facial edema including the SVCS. We emphasize the

Manuela Yuste Chaves; Juan Carlos Santos Durán; Juan Sánchez Estella

271

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.  

PubMed

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

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

2015-01-15

272

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

PubMed Central

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

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

2015-01-01

273

MAGNESIUM SULFATE REDUCES INFLAMMATION-ASSOCIATED BRAIN INJURY IN FETAL MICE  

PubMed Central

OBJECTIVE To investigate whether magnesium sulfate (MgSO4) prevents fetal brain injury in inflammation-associated preterm birth (PTB). STUDY DESIGN Utilising a mouse model of PTB, LPS or normal saline (NS)-exposed mice via intrauterine injection, were randomized to intraperitoneal treatment with MgSO4 or NS. From the 4 treatment groups, 1)NS+NS; 2)LPS+NS; 3)LPS+MgSO4; and 4)NS+MgSO4, fetal brains were collected for QPCR studies and primary neuronal cultures. mRNA expression of cytokines, cell death, and markers of neuronal and glial differentiation were assessed. Immunocytochemistry and confocal microscopy were performed. RESULTS There was no difference between LPS+NS and LPS+MgSO4 groups in expression of pro-inflammatory cytokines, cell death markers as well markers of pro-oligodendrocyte and astrocyte development (P>0.05 for all). Neuronal cultures from LPS+NS demonstrated morphological changes and this neuronal injury was prevented by MgSO4 (P<0.001). CONCLUSION Amelioration of neuronal injury in inflammation-associated PTB may be a key mechanism by which MgSO4 prevents cerebral palsy. PMID:20207246

Burd, Irina; Breen, Kelsey; Friedman, Alexander; Chai, Jinghua; Elovitz, Michal A.

2010-01-01

274

Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels  

PubMed Central

Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca2+-activated K+ channel (BKCa) channels, and BKCa channel blockade suppressed the neuroprotection of the extract, suggesting that the BKCa is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BKCa channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BKCa channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BKCa channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia. PMID:21364615

Chi, S; Cai, W; Liu, P; Zhang, Z; Chen, X; Gao, L; Qi, J; Bi, L; Chen, L; Qi, Z

2010-01-01

275

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain.  

PubMed

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID:22058426

Larsen, Scott D; Wilson, Michael W; Abe, Akira; Shu, Liming; George, Christopher H; Kirchhoff, Paul; Showalter, H D Hollis; Xiang, Jianming; Keep, Richard F; Shayman, James A

2012-02-01

276

Reducing Inhomogeneity Artifacts in Functional MRI of Human Brain Activation—Thin Sections vs Gradient Compensation  

NASA Astrophysics Data System (ADS)

We evaluated two methods for correcting inhomogeneity-induced signal losses in magnetic resonance gradient-echo imaging that either use gradient compensation or simply acquire thin sections. The strategies were tested in the human brain in terms of achievable quality of T2*-weighted images at the level of the hippocampus and of functional activation maps of the visual cortex. Experiments were performed at 2.0 T and based on single-shot echo-planar imaging at 2.0 × 2.0 mm2 resolution, 4 mm section thickness, and 2.0 s temporal resolution. Gradient compensation involved a sequential 16-step variation of the refocusing lobe of the slice-selection gradient (TR/TE = 125/53 ms, flip angle 15°), whereas thin sections divided the 4-mm target plane into either four 1-mm or eight 0.5-mm interleaved multislice acquisitions (TR/TE = 2000/54 ms, flip angle 70°). Both approaches were capable of alleviating the inhomogeneity problem for structures in the base of the brain. When compared to standard 4-mm EPI, functional mapping in the visual cortex was partially compromised because of a lower signal-to-noise ratio of inhomogeneity-corrected images by either method. Relative to each other, consistently better results were obtained with the use of contiguous thin sections, in particular for a thickness of 1 mm. Multislice acquisitions of thin sections require minimal technical adjustments.

Merboldt, Klaus-Dietmar; Finsterbusch, Jürgen; Frahm, Jens

2000-08-01

277

[Histochemical and ultrastructural studies on the anti-edema and radiation-protective effects of 0-(beta-hydroxyethyl)-rutosides in the rat brain after single-dose irradiation. 1. Electron microscopy study of terminal blood circulation].  

PubMed

The changes in the terminal blood stream appeared with and without protection by 0-(beta-hydroxyethyl)-rutoside (HR) were studied in irradiated rat brains by means of the electron and light microscope. Thirty minutes before irradiating the animals with doses of 1, 5, 10, and 20 Gy, they were given simultaneous i.p. and s.c. doses of 250 mg each of HR per kg of body weight or, as a control, of physiologic NaCl solution. 2, 6, 9, and 14 days after the irradiation, small tissue specimens from the parasagittal parietal cortex were examined according to the following criteria: 1. number of widely open, i.e. well perfused capillaries and small vessels, 2. number and size of perivascular, optically unstructured "light haloes" which are signs of intracellular oedemas of the perivascular astrocyte processes, 3. incidence of hyperchromic, partly shrunken neurons. The control animals not pretreated with HR showed a collapse of most capillaries and an increase in number and size of "light haloes" around capillaries, arterioles and venules. In the electron microscope, these haloes corresponded to the strongly swollen parts of the perivascular neuropile consisting mainly of oedematous astrocyte processes. These severe perivascular cell alterations were prevented for all dose ranges by the pretreatment with HR. Thus our findings do not only demonstrate a clear antiedematous effect of HR on the radiogenic cell oedema of the perivascular neuropile, they support moreover the working hypotheses with regard to the mode of action of this substance as a "membrane protector". PMID:3175854

Thiel, H J; Hammersen, F; Sauer, R

1988-09-01

278

Arm edema in breast cancer patients.  

PubMed

The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions. PMID:11208879

Erickson, V S; Pearson, M L; Ganz, P A; Adams, J; Kahn, K L

2001-01-17

279

Bilateral leg edema in an older woman.  

PubMed

Bilateral leg edema is a frequent symptom in older people and an important concern in geriatric medicine. Further evaluation is frequently not performed and simple therapy with diuretics is prescribed. Particularly in older patients, long-term use of diuretics can lead to severe electrolyte imbalances, volume depletion, and falls. In this case report we want to focus the physicians' attention on the necessity to determine the cause and show a correspondingly effective treatment for bilateral leg edema in older people. A thorough approach is required to recognize diseases and to avoid adverse drug events as geriatric patients often show an atypical presentation or minor symptoms. The cause of swollen legs is often multifactorial; therefore, the patient's individual history and an appropriate physical examination are important. Depending on the clinical symptoms, evaluation including basic laboratory tests, urinalysis, chest radiography, and echocardiogram may be indicated. The most probable cause of bilateral edema in older patients is chronic venous insufficiency. Heart failure is also a common cause. Other systemic causes such as renal disease or liver disease are much rarer. Antihypertensive and anti-inflammatory drugs can frequently cause leg edema, but the incidence of drug-induced leg swelling is unknown. With the help of this special case we tried to develop an approach to the diagnosis of symmetric leg edema in older patients, a problem frequently neglected in geriatric medicine. PMID:24271146

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

2015-01-01

280

Nanoparticulate flurbiprofen reduces amyloid-?42 generation in an in vitro blood–brain barrier model  

PubMed Central

Introduction The amyloid-?42 (A?42) peptide plays a crucial role in the pathogenesis of Alzheimer’s disease (AD), the most common neurodegenerative disorder affecting the elderly. Over the past years, several approaches and compounds developed for the treatment of AD have failed in clinical studies, likely in part due to their low penetration of the blood–brain barrier (BBB). Since nanotechnology-based strategies offer new possibilities for the delivery of drugs to the brain, this technique is studied intensively for the treatment of AD and other neurological disorders. Methods The A?42 lowering drug flurbiprofen was embedded in polylactide (PLA) nanoparticles by emulsification-diffusion technique and their potential as drug carriers in an in vitro BBB model was examined. First, the cytotoxic potential of the PLA-flurbiprofen nanoparticles on endothelial cells and the cellular binding and uptake by endothelial cells was studied. Furthermore, the biological activity of the nanoparticulate flurbiprofen on ?-secretase modulation as well as its in vitro release was examined. Furthermore, the protein corona of the nanoparticles was studied as well as their ability to transport flurbiprofen across an in vitro BBB model. Results PLA-flurbiprofen nanoparticles were endocytosed by endothelial cells and neither affected the vitality nor barrier function of the endothelial cell monolayer. The exposure of the PLA-flurbiprofen nanoparticles to human plasma occurred in a rapid protein corona formation, resulting in their decoration with bioactive proteins, including apolipoprotein E. Furthermore, luminally administered PLA-flurbiprofen nanoparticles in contrast to free flurbiprofen were able to modulate ?-secretase activity by selectively decreasing A?42 levels in the abluminal compartment of the BBB model. Conclusions In this study, we were able to show that flurbiprofen can be transported by PLA nanoparticles across an in vitro BBB model and most importantly, the transported flurbiprofen modulated ?-secretase activity by selectively decreasing A?42 levels. These results demonstrate that the modification of drugs via embedding in nanoparticles is a promising tool to facilitate drug delivery to the brain, which enables future development for the treatment of neurodegenerative disorders like AD. PMID:24280275

2013-01-01

281

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

PubMed

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the (131)Cs, (125)I and (103)Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using (125)I sources was less affected by edema than PIB using (131)Cs or (103)Pd sources due to the long radioactive decay half-life of (125)I. The effect of edema on PIB using (131)Cs or (103)Pd was similar. The effect of edema on (103)Pd PIB was slightly greater, even though the decay half-life of (103)Pd (17 days) is longer than that of (131)Cs (9.7 days), because the advantage of the longer (103)Pd decay half-life was negated by the lower effective energy of the photons it emits (?21 keV compared to ?30.4 keV for (131)Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the ?/? ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer. PMID:21772076

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

2011-08-01

282

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

NASA Astrophysics Data System (ADS)

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

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

2011-08-01

283

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers  

PubMed Central

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than that of 131Cs (9.7 days), because the advantage of the longer 103Pd decay half-life was negated by the lower effective energy of the photons it emits (~21 keV compared to ~30.4 keV for 131Cs). In addition, the impact of edema could be reduced or enhanced by differences in the tumor characteristics (e.g. potential tumor doubling time or the ?/? ratio), and the effect of these factors varied for the different radioactive sources. There is a clear need to consider the effects of prostate edema during the planning and evaluation of permanent interstitial brachytherapy treatments for prostate cancer. PMID:21772076

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

2011-01-01

284

Diabetic papillopathy with macular edema treated with intravitreal ranibizumab  

PubMed Central

We report a case of diabetic papillopathy that demonstrated a resolution of optic disk swelling and rapid visual recovery when intravitreal ranibizumab was administered. A 51-year-old male presented with acute painless visual loss in his right eye. His vision was 20/320 in the right eye and 20/50 in the left eye. Fundus examination of the right eye showed nonproliferative diabetic retinopathy with macular edema and a swollen optic disk. Fluorescein angiography showed dye leakage from the right optic disk. Optical coherent tomography revealed a significant increase in retinal nerve fiber-layer thickness. Magnetic resonance imaging of the brain was normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks following injection, there was marked regression of the disk swelling and improvement of macular edema, with vision improving to 20/100. Three months following injection, there was complete resolution of the optic disk swelling. No further treatment was required. PMID:24348012

Kim, Moosang; Lee, Jang-Hun; Lee, Seung-Jun

2013-01-01

285

Hereditary angioneurotic edema with severe hypovolemic shock.  

PubMed

Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients. PMID:8505498

Cohen, N; Sharon, A; Golik, A; Zaidenstein, R; Modai, D

1993-04-01

286

Combined Therapy for Diabetic Macular Edema  

PubMed Central

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. The management of DME is complex and often multiple treatment approaches are needed. This review demonstrates the benefits of intravitreal triamcinolone, bevacizumab and ranibizumab as adjunctive therapy to macular laser treatment in DME. The published results indicate that intravitreal injections of these agents may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present. Therefore, pharmacotherapy could complement focal/grid laser photocoagulation in the management of DME. For this review, we performed a literature search and summarized recent findings regarding combined therapy for DME. PMID:24339681

Al Rashaed, Saba; Arevalo, J. Fernando

2013-01-01

287

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

PubMed Central

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

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

2015-01-01

288

Cyclooxygenase-2 Mediates Hyperbaric Oxygen Preconditioning Induced Neuroprotection in the Mouse Model of Surgical Brain Injury  

PubMed Central

Background and Purpose: We investigated the role of cyclooxygenase-2 (COX-2) in mechanisms of hyperbaric oxygen preconditioning (HBO-PC) in the mouse model of surgical brain injury (SBI). Methods: C57BL mice were administered 100% oxygen for 1 hr at 2.5 ATA for 5 consecutive days and subjected to SBI. Neurological status and brain edema were evaluated at 24 hrs and 72 hrs after the brain insult. Fluorescent immunostaining and Western blotting were performed to study hypoxia inducible factor-1? (HIF-1?) and COX-2, respectively. Two doses of COX-2 inhibitor, NS398 (3mg/kg and 10mg/kg) were used to verify the role of COX-2 signaling pathway in the mechanism of HBO-PC. Results: HBO-PC improved neurological status and decreased brain edema at 24hrs and 72hrs after SBI. HBO-PC by itself and SBI independently increased COX-2 levels by 2-fold and 4-fold respectively. HBO-PC however reduced increase in HIF-1? and COX-2 expression after SBI. The HBO-PC-induced improvement in neurological status and brain edema was reversed by suboptimal dose of COX-2 inhibitor, NS398 (10mg/kg, i.p; 1/4th of dose shown to provide neuroprotection), which itself had no effect on investigated endpoints. Conclusions: HBO-PC attenuates post-operative brain edema and improves neurological outcomes following SBI. The HBO-PC induced neuroprotection is mediated via COX-2 signaling pathways. PMID:19628811

Jadhav, Vikram; Ostrowski, Robert P.; Tong, Wenni; Matus, Brenden; Jesunathadas, Rachel; Zhang, John H.

2009-01-01

289

Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema  

PubMed Central

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

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

2013-01-01

290

Brain injury-induced proteolysis is reduced in a novel calpastatin overexpressing transgenic mouse  

PubMed Central

The calpain family of calcium-dependent proteases has been implicated in a variety of diseases and neurodegenerative pathologies. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components and membrane receptors, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains. Pharmacological and gene knockout strategies have targeted calpains to determine their contribution to neurodegenerative pathology; however, limitations associated with treatment paradigms, drug specificity, and genetic disruptions have produced inconsistent results and complicated interpretation. Specific, targeted calpain inhibition achieved by enhancing endogenous calpastatin levels offers unique advantages in studying pathological calpain activation. We have characterized a novel calpastatin overexpressing transgenic mouse model, demonstrating a substantial increase in calpastatin expression within nervous system and peripheral tissues and associated reduction in protease activity. Experimental activation of calpains via traumatic brain injury resulted in cleavage of ?-spectrin, collapsin response mediator protein-2, and voltage-gated sodium channel, critical proteins for the maintenance of neuronal structure and function. Calpastatin overexpression significantly attenuated calpain-mediated proteolysis of these selected substrates acutely following severe controlled cortical impact injury, but with no effect on acute hippocampal neurodegeneration. Augmenting calpastatin levels may be an effective method for calpain inhibition in TBI and neurodegenerative disorders. PMID:23305291

Schoch, Kathleen M.; von Reyn, Catherine R.; Bian, Jifeng; Telling, Glenn C.; Meaney, David F.; Saatman, Kathryn E.

2013-01-01

291

Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer’s disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (A?) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in A? depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI. PMID:24413756

Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J.; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V.; Sanberg, Paul R.; Tan, Jun

2014-01-01

292

Activation of liver X receptor reduces global ischemia brain injury by reduction of nuclear factor-?B  

PubMed Central

Recent studies have found that liver X receptors (LXRs) agonists decrease inflammation and possess neuroprotective properties. The aim of this study was to examine the mechanisms of liver X receptor agonist GW3965 on brain injury following global cerebral ischemia in the rat. The 48 male SD rats were randomly partitioned into three groups: sham, global ischemia (4-vessel occlusion for 15 minutes; 4VO) treated with vehicle and global ischemia treated with GW3965 (20mg/kg, via i.p at 10 minutes after reperfusion). The functional outcome was determined by neurological evaluation at 24 hours post ischemia and by testing rats in T maze at 3 and 7 days after reperfusion. The rats' daily body weight, incidence of seizures and 72 hours mortality were also determined. After Nissl staining and TUNEL in coronal brain sections, the numbers of intact and damaged cells were counted in the CA1 sector of the hippocampus. The expression of phosphorylated inhibitor of ?B (p-I?B?), Nuclear Factor-?B (NF-?B) subunit p65, and cyclo-oxygenase-2 (COX-2) were analyzed with Western blot at 12 hours after reperfusion. GW3965 tended to reduce 72 hours mortality and the incidence of post-ischemic seizures. GW3965-treated rats showed an improved neuronal survivability in CA1 and a significant increase in the percentage of spontaneous alternations detected in T-maze on day 7 after ischemia. GW3965-induced neuroprotection was associated with a significant reduction in nuclear translocation of NF-kB p65 subunit and a decrease in the hippocampal expression of NF-kB target gene, COX-2. LXR receptor agonist protects against neuronal damage following global cerebral ischemia. The mechanism of neuroprotection may include blockade of NF-?B activation and the subsequent suppression of COX-2 in the post ischemic brain. PMID:20096333

Cheng, Oumei; Ostrowski, Robert P.; Liu, Wenwu; Zhang, John H.

2010-01-01

293

Treatment with a monoclonal antibody against methamphetamine and amphetamine reduces maternal and fetal rat brain concentrations in late pregnancy.  

PubMed

We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ?15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP. PMID:24839971

White, Sarah J; Hendrickson, Howard P; Atchley, William T; Laurenzana, Elizabeth M; Gentry, W Brooks; Williams, D Keith; Owens, S Michael

2014-08-01

294

Protective Ventilation of Preterm Lambs Exposed to Acute Chorioamnionitis Does Not Reduce Ventilation-Induced Lung or Brain Injury  

PubMed Central

Background The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. Methods Pregnant ewes (n?=?18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n?=?6), or were ventilated using an injurious high VT strategy (LPSINJ; n?=?5) or a protective ventilation strategy (LPSPROT; n?=?7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. Results LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. Conclusions Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis. PMID:25379714

Barton, Samantha K.; Moss, Timothy J. M.; Hooper, Stuart B.; Crossley, Kelly J.; Gill, Andrew W.; Kluckow, Martin; Zahra, Valerie; Wong, Flora Y.; Pichler, Gerhard; Galinsky, Robert; Miller, Suzanne L.

2014-01-01

295

UNCORRECTEDPROOF 2 A brain tumor segmentation framework based on outlier detection q  

E-print Network

brain tumor segmentation from MR images. The detection of edema is done 10 simultaneously with tumor segmentation, as the knowledge of the extent of edema is important for diagnosis, planning, and 11 treatment whether edema appears together with tumor in the abnormal regions. 18 Finally, we apply geometric

296

A3 Adenosine Receptor Agonist Reduces Brain Ischemic Injury and Inhibits Inflammatory Cell Migration in Rats  

PubMed Central

A3 adenosine receptor (A3AR) is recognized as a novel therapeutic target for ischemic injury; however, the mechanism underlying anti-ischemic protection by the A3AR agonist remains unclear. Here, we report that 2-chloro-N6-(3-iodobenzyl)-5?-N-methylcarbamoyl-4?-thioadenosine (LJ529), a selective A3AR agonist, reduces inflammatory responses that may contribute to ischemic cerebral injury. Postischemic treatment with LJ529 markedly reduced cerebral ischemic injury caused by 1.5-hour middle cerebral artery occlusion, followed by 24-hour reperfusion in rats. This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. LJ529 prevented the infiltration/migration of microglia and monocytes occurring after middle cerebral artery occlusion and reperfusion, and also after injection of lipopolysaccharides into the corpus callosum. The reduced migration of microglia by LJ529 could be related with direct inhibition of chemotaxis and down-regulation of spatiotemporal expression of Rho GTPases (including Rac, Cdc42, and Rho), rather than by biologically relevant inhibition of inflammatory cytokine/chemokine release (eg, IL-1?, TNF-?, and MCP-1) or by direct inhibition of excitotoxicity/oxidative stress (not affected by LJ529). The present findings indicate that postischemic activation of A3AR and the resultant reduction of inflammatory response should provide a promising therapeutic strategy for the treatment of ischemic stroke. PMID:21854743

Choi, In-Young; Lee, Jae-Chul; Ju, Chung; Hwang, Sunyoung; Cho, Geum-Sil; Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin; Kim, Won-Ki

2011-01-01

297

Reduced glucose uptake and A? in brain regions with hyperintensities in connected white matter.  

PubMed

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (? = 0.045) and FDG-PET (? = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition. PMID:24999038

Glodzik, L; Kuceyeski, A; Rusinek, H; Tsui, W; Mosconi, L; Li, Y; Osorio, R S; Williams, S; Randall, C; Spector, N; McHugh, P; Murray, J; Pirraglia, E; Vallabhajosula, S; Raj, A; de Leon, M J

2014-10-15

298

Traumatic brain injury reduces striatal tyrosine hydroxylase activity and potassium-evoked dopamine release in rats  

PubMed Central

There is increasing evidence that traumatic brain injury (TBI) induces hypofunction of the striatal dopaminergic system, the mechanisms of which are unknown. In this study, we analyzed the activity of striatal tyrosine hydroxylase (TH) in rats at 1 day, 1 week, and 4 weeks after TBI using the controlled cortical impact model. There were no changes in the level of TH phosphorylated at serine 40 site (pser40TH) at 1 day or 4 weeks. At 1 week, injured animals showed decreased pser40TH to 73.9±7.3% (p?0.05) of sham injured rats. The in vivo TH activity assay showed no significant difference between injured and sham rats at 1 day. However, there was a decreased activity in injured rats to 62.1±8.2% (p?0.05) and 68.8±6.2% (p?0.05) of sham injured rats at 1 and 4 weeks, respectively. Also, the activity of protein kinase A, which activates TH, decreased at 1 week (injured: 87.8±2.8%, sham: 100.0± 4.2%, p?0.05). To study the release activity of dopamine after injury, potassium (80 mM)-evoked dopamine release was measured by microdialysis in awake, freely moving rats. Dialysates were collected and analyzed by high-performance liquid chromatography. There were no significant differences in dopamine release at 1 day and 4 weeks between sham and injured groups. At 1 week, there was a significant decrease (injured: 0.067±0.015 ?M, sham: 0.127 ± 0.027 ?M, p ? 0.05). These results suggest that TBI-induced dopamine neurotransmission deficits are, at least in part, attributable to deficits in TH activity. PMID:21047500

Shin, Samuel S.; Bray, Eric R.; Zhang, Cathy Q.; Dixon, C. Edward

2010-01-01

299

Retinal microvascular damage and vasogenic edema produced by Clostridium perfringens type D epsilon toxin in rats.  

PubMed

When the brain is exposed to large circulating levels of Clostridium perfringens type D epsilon toxin (EXT), microvascular damage with resulting severe, generalized, vasogenic edema seems to be principally responsible for the ensuing acute, and frequently fatal, neurologic disorder. However, although the blood-retinal barrier resembles in many respects the blood-brain barrier, retinal changes in livestock with acute epsilon intoxication have not, to the authors' knowledge, been previously reported. In rats given an acute dose of ETX, retinal microvascular endothelial injury led to widespread vasogenic edema as assessed immunohistochemically by marked plasma albumin extravasation. As laboratory rodents are a good model of the domestic livestock disease produced by ETX, it is probable that the latter sustain some visual deficit when exposed to large doses of this potent neurotoxin. PMID:24741023

Finnie, John W; Manavis, Jim; Casson, Robert J; Chidlow, Glyn

2014-04-16

300

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

PubMed Central

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

2011-01-01

301

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

E-print Network

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

Moss, W C; Blackman, E G

2012-01-01

302

Hereditary Angioneurotic Edema: Two Genetic Variants  

Microsoft Academic Search

Serums of patients with hereditary angioneurotic edema lack inhibitory activity against the esterase derived from the first component of complement. In one group of patients this lack appears to result from failure to synthesize the esterase inhibitor of the first component of complement, whereas in another group of patients an abnormal, nonfunctional protein is synthesized.

Fred S. Rosen; Patricia Charache; Jack Pensky; Virginia Donaldson

1965-01-01

303

Pulmonary Edema Develops after Recurrent Obstructive Apneas  

Microsoft Academic Search

There are anecdotal reports of pulmonary edema after a night of recurrent obstructive apneas (OAs) in humans, but no data on lung water, gas exchange, filling pressure, or cardiac output ( ) exist in these patients. By clamping the endotracheal tube of eight intubated, anesthesized dogs, we created repetitive OAs of 45-s duration at 30-s intervals, for 8 h. Five

EUGENE C. FLETCHER; MARY PROCTOR; JERRY YU; JUFANG ZHANG; JUAN J. GUARDIOLA; CARLTON HORNUNG; GANG BAO

1999-01-01

304

Steroids and the Management of Macular Edema  

Microsoft Academic Search

Macular edema (ME) is a condition which is usually secondary to an underlying disease process. It is most commonly seen following venous occlusive disease, diabetic retinopathy and posterior segment inflammatory disease. The treatment of ME varies, depending upon the underlying etiology, and has led to varying degrees of success. Traditionally, the main treatment options have included topical and systemic steroids,

Shani Golan; Anat Loewenstein

2010-01-01

305

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

PubMed

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

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

2013-08-01

306

A Reduced Astrocyte Response to ?-Amyloid Plaques in the Ageing Brain Associates with Cognitive Impairment  

PubMed Central

Aims ?-amyloid (A?) plaques are a key feature of Alzheimer’s disease pathology but correlate poorly with dementia. They are associated with astrocytes which may modulate the effect of A?-deposition on the neuropil. This study characterised the astrocyte response to A? plaque subtypes, and investigated their association with cognitive impairment. Methods A? plaque subtypes were identified in the cingulate gyrus using dual labelling immunohistochemistry to A? and GFAP+ astrocytes, and quantitated in two cortical areas: the area of densest plaque burden and the deep cortex near the white matter border (layer VI). Three subtypes were defined for both diffuse and compact plaques (also known as classical or core-plaques): A? plaque with (1) no associated astrocytes, (2) focal astrogliosis or (3) circumferential astrogliosis. Results In the area of densest burden, diffuse plaques with no astrogliosis (? = -0.05, p = 0.001) and with focal astrogliosis (? = -0.27, p = 0.009) significantly associated with lower MMSE scores when controlling for sex and age at death. In the deep cortex (layer VI), both diffuse and compact plaques without astrogliosis associated with lower MMSE scores (? = -0.15, p = 0.017 and ? = -0.81, p = 0.03, respectively). Diffuse plaques with no astrogliosis in layer VI related to dementia status (OR = 1.05, p = 0.025). In the area of densest burden, diffuse plaques with no astrogliosis or with focal astrogliosis associated with increasing Braak stage (? = 0.01, p<0.001 and ? = 0.07, p<0.001, respectively), and ApoE?4 genotype (OR = 1.02, p = 0.001 and OR = 1.10, p = 0.016, respectively). In layer VI all plaque subtypes associated with Braak stage, and compact amyloid plaques with little and no associated astrogliosis associated with ApoE?4 genotype (OR = 1.50, p = 0.014 and OR = 0.10, p = 0.003, respectively). Conclusions Reactive astrocytes in close proximity to either diffuse or compact plaques may have a neuroprotective role in the ageing brain, and possession of at least one copy of the ApoE?4 allele impacts the astroglial response to A? plaques. PMID:25707004

Mathur, Ryan; Ince, Paul G.; Minett, Thais; Garwood, Claire J.; Shaw, Pamela J.; Matthews, Fiona E.; Brayne, Carol

2015-01-01

307

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

PubMed

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

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

2014-05-15

308

Emotional graphic cigarette warning labels reduce the electrophysiological brain response to smoking cues.  

PubMed

There is an ongoing public debate about the new graphic warning labels (GWLs) that the Food and Drug Administration (FDA) proposes to place on cigarette packs. Tobacco companies argued that the strongly emotional images FDA proposed to include in the GWLs encroached on their constitutional rights. The court ruled that FDA did not provide sufficient scientific evidence of compelling public interest in such encroachment. This study's objectives were to examine the effects of the GWLs on the electrophysiological and behavioral correlates of smoking addiction and to determine whether labels rated higher on the emotional reaction (ER) scale are associated with greater effects. We studied 25 non-treatment-seeking smokers. Event-related potentials (ERPs) were recorded while participants viewed a random sequence of paired images, in which visual smoking (Cues) or non-smoking (non-Cues) images were preceded by GWLs or neutral images. Participants reported their cigarette craving after viewing each pair. Dependent variables were magnitude of P300 ERPs and self-reported cigarette craving in response to Cues. We found that subjective craving response to Cues was significantly reduced by preceding GWLs, whereas the P300 amplitude response to Cues was reduced only by preceding GWLs rated high on the ER scale. In conclusion, our study provides experimental neuroscience evidence that weighs in on the ongoing public and legal debate about how to balance the constitutional and public health aspects of the FDA-proposed GWLs. The high toll of smoking-related illness and death adds urgency to the debate and prompts consideration of our findings while longitudinal studies of GWLs are underway. PMID:24330194

Wang, An-Li; Romer, Dan; Elman, Igor; Strasser, Andrew A; Turetsky, Bruce I; Gur, Ruben C; Langleben, Daniel D

2015-03-01

309

Generalized edema associated with parvovirus B19 infection.  

PubMed

Generalized edema is a rare presentation of human parvovirus B19 infection. The etiology of this edema is unclear, particularly because signs of heart or renal failure are often not present. We report the case of a young adult presenting with generalized edema with serological and PCR evidence of parvovirus B19 infection, and discuss the potential mechanisms of edema based on the previous literature. PMID:25449233

Vlaar, Pieter J; Mithoe, Glen; Janssen, Wilbert M

2014-12-01

310

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

NASA Astrophysics Data System (ADS)

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

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

2008-03-01

311

Reduced Intestinal Brain-Derived Neurotrophic Factor Increases Vagal Sensory Innervation of the Intestine and Enhances Satiation  

PubMed Central

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF?/?) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF?/? mice were increased, but stomach IGLEs were normal. INT-BDNF?/? mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF?/? mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF?/? mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF?/? mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF?/? mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF?/? mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. PMID:25080597

Biddinger, Jessica E.

2014-01-01

312

IMAGING OF PULMONARY EDEMA WITH ELECTRICAL IMPEDANCE TOMOGRAPHY  

E-print Network

IMAGING OF PULMONARY EDEMA WITH ELECTRICAL IMPEDANCE TOMOGRAPHY Andy ADLER , Yves BERTHIAUME in studying pulmonary edema as the clinical phenomena of interest induce large conductivity changes. We have of pulmonary edema (PE) in humans is difficult since there is no non-invasive technique that would allow

Adler, Andy

313

In vivo photoacoustic tomography of mouse cerebral edema induced  

E-print Network

In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury Zhun Xu Quing Zhu cerebral edema induced by cold injury Zhun Xu,a Quing Zhu,b and Lihong V. Wanga aWashington University. For the first time, we have implemented photoacoustic tomography (PAT) to image the water content of an edema

Wang, Lihong

314

Chronic Salicylism Resulting in Noncardiogenic Pulmonary Edema Requiring Hemodialysis  

Microsoft Academic Search

Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We describe a 42-year-old woman who presented with two episodes of recurrent noncardiogenic pulmonary edema requiring intubation. The first admission to hospital triggered an extensive initial workup that did not indicate a cause for the pulmonary edema. At the second presentation,

Debbie L. Cohen; Jarrod Post; Anthony A. Ferroggiaro; Jeanmarie Perrone; Mary H. Foster

2000-01-01

315

Localization of dermal edema in lipodermatosclerosis, lymphedema, and cardiac insufficiency  

Microsoft Academic Search

Background: Chronic edema in venous insufficiency is associated with leg ulceration, whereas in lymphedema skin ulceration is less frequent and edema from cardiac failure does not cause major skin changes. The reason for these differences is unclear.Objective: Our purpose was to investigate, by means of ultrasound, the distribution of intradermal fluid in patients with edema associated with lipodermatosclerosis, lymphedema, or

Monika Gniadecka

1996-01-01

316

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

SciTech Connect

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

Testylier, Guy [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France)]. E-mail: guytestylier@crssa.net; Lahrech, Hana [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Montigon, Olivier [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Foquin, Annie [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Delacour, Claire [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Bernabe, Denis [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Segebarth, Christoph [Inserm, UMR-S 836-Grenoble Institut des Neurosciences, Grenoble, F-38043 (France); Universite Joseph Fourier, Grenoble, F-38043 (France); Dorandeu, Frederic [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France); Carpentier, Pierre [Centre de Recherches du Service Sante des Armees, Departement de Toxicologie, BP87, F-38702 La Tronche cedex (France)

2007-04-15

317

Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain.  

PubMed

The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1? and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation. PMID:24373829

Ahmad, Aliya; Ramasamy, Kalavathy; Jaafar, Siti Murnirah; Majeed, Abu Bakar Abdul; Mani, Vasudevan

2014-03-01

318

Prognosis for Severe Traumatic Brain Injury Patients Treated with Bilateral Decompressive Craniectomy  

Microsoft Academic Search

\\u000a \\u000a Purpose  Decompressive craniectomy for traumatic brain injury patients has been shown to reduce intracranial hypertension, while it\\u000a often results in increased brain edema and\\/or contralateral space-occupied hematoma. The purpose of this study was to determine\\u000a the prognosis of bilateral decompressive craniectomy in severe head injury patients with the development of either bilateral\\u000a or contralateral lesions after ipsilateral decompressive craniectomy.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twelve patients

Hiroshi Yatsushige; Yoshio Takasato; Hiroyuki Masaoka; Takanori Hayakawa; Naoki Otani; Yoshikazu Yoshino; Kyoko Sumiyoshi; Takashi Sugawara; Hiroki Miyawaki; Chikashi Aoyagi; Satoru Takeuchi; Go Suzuki

319

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

E-print Network

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

320

Treatment and functional outcome of patients with cystoid macular edema: a single-center experience.  

PubMed

The aim of this study was to describe a single-center experience in the treatment and follow-up of cystoid macular edema patients. Clinical records of all patients with cystoid macular edema followed up in the Rheumatologic and Ophthalmological Unit of our center between 1993 and 2013 were retrospectively evaluated. The outcome was assessed by visual acuity and optical coherence tomography status during follow-up. Comparisons were made by Fisher's exact test (p?reducing macular edema. At the end of follow-up, 50 % of patients showed a significant visual loss, while 88 % did not present macular edema. In our small cohort, interferon-? is the most promising drug in contrasting visual acuity loss in cystoid macular edema. Visual prognosis remains severe in these patients. PMID:25028250

Taraborelli, Mara; Cavazzana, Ilaria; Fredi, Micaela; Airò, Paolo; Nascimbeni, Giuseppe; Tincani, Angela; Franceschini, Franco

2015-04-01

321

Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces A? level and microglia activation in the brains of 3xTg-AD mice.  

PubMed

Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced A?40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD. PMID:24918340

Chen, Yanxing; Zhao, Yang; Dai, Chun-Ling; Liang, Zhihou; Run, Xiaoqin; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

2014-11-01

322

Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.  

PubMed

In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2?, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

2014-03-01

323

Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury  

PubMed Central

Background and purpose: Traumatic brain injury (TBI) triggers a complex series of inflammatory responses that contribute to secondary tissue damage. The aim of this study was to investigate the effect of baicalein, a flavonoid possessing potent anti-inflammatory properties, on functional and histological outcomes and inflammatory cytokine expression, following TBI in rats. Experimental approach: Rats subjected to controlled cortical impact injury were injected with baicalein (30?mg?kg?1) or vehicle immediately after injury or daily for 4 days. Neurological status was evaluated using the rotarod, adhesive removal, modified neurological severity scores and beam walk tests. Contusion volume and neuronal degeneration were measured using cresyl violet and FluoroJade B (FJB) histochemistry. Levels of tumour necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and interleukin-6 (IL-6) mRNA and protein were assessed by real-time quantitative reverse transcriptase-PCR, enzyme-linked immunosorbent assay and immunohistochemistry. Key results: Single-dose and multiple-dose treatment with baicalein significantly improved functional recovery and reduced contusion volumes up to day 28 post-injury, although multiple-dose baicalein was the more effective treatment. Single-dose baicalein also significantly reduced the number of degenerating neurons (31%) on post-injury day 1 as indicated by FJB staining. These changes were associated with significantly decreased levels, at the contusion site, of TNF-?, IL-1? and IL-6 mRNA at 6?h, and cytokine protein on day 1 post-injury. Conclusions and implications: Post-injury treatment with baicalein improved functional and histological outcomes and reduced induction of proinflammatory cytokines in rat TBI. The neuroprotective effect of baicalein may be related to a decreased inflammatory response following the injury. PMID:18776918

Chen, S-F; Hsu, C-W; Huang, W-H; Wang, J-Y

2008-01-01

324

Hypothyroidism and non-cardiogenic pulmonary edema: are we missing something here?  

PubMed Central

Summary We report the case of a 42-year-old female with a history of hypothyroidism and asthma presenting with progressive dyspnea and orthopnea after 2 days of an upper respiratory tract infection (URTI). Based on the clinical and radiological findings, the patient was admitted as a case of cardiogenic pulmonary edema secondary to possible viral myocarditis. However, a normal brain natriuretic peptide (BNP) level with a normal ejection fraction (EF) on echocardiogram changed our working diagnosis from cardiogenic to non-cardiogenic pulmonary edema. Further questioning revealed a history of nocturnal snoring, frequent awakening, and daytime fatigue, suggesting a possible sleep apnea syndrome (SAS). In conclusion, we believe that SAS was the missing link between our patient's hypothyroidism and non-cardiogenic pulmonary edema. Learning points Always keep an open mind and look for a pathology that would explain the whole clinical scenario.The involvement of the respiratory system in hypothyroidism can range from SAS, pulmonary hypertension, hypoventilation, and severe respiratory failure.Hypothyroidism and SAS should be considered in the differential diagnosis of non-cardiogenic pulmonary edema.Patients should be instructed to take levothyroxine on an empty stomach 30–60?min before food to avoid erratic absorption of the hormone. PMID:25866647

Nikolla, Dhimitri; Metta, V V S Ramesh

2015-01-01

325

Impact of Clipping versus Coiling on Postoperative Hemodynamics and Pulmonary Edema after Subarachnoid Hemorrhage  

PubMed Central

Volume management is critical for assessment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This multicenter prospective cohort study compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema in patients with SAH. Hemodynamic parameters were measured for 14 days using a transpulmonary thermodilution system. The study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF), cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were significantly higher in the clipping group in the vasospasm period. Postoperative C-reactive protein (CRP) level was higher in the clipping group and was significantly correlated with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema, and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the vasospasm period, suggesting noncardiogenic edema. In conclusion, clipping affects postoperative CRP level and may thereby increase noncardiogenic pulmonary edema in the vasospasm period. His trial is registered with University Hospital Medical Information Network UMIN000003794. PMID:24818154

Horie, Nobutaka; Iwaasa, Mitsutoshi; Ishizaka, Shunsuke; Inoue, Tooru; Nagata, Izumi

2014-01-01

326

Acute pulmonary edema after near strangulation  

Microsoft Academic Search

We report a case of acute, noncardiogenic pulmonary edema in an 11-year-old boy who suffered strangulation during an altercation.\\u000a The clinical presentation was characterized by moderate respiratory distress and hemoptysis. Both the radiographic and clinical\\u000a findings resolved during the three day admission which followed. A review of the literature is presented, and possible pathogenesis\\u000a is discussed.

D. Shumaker; S. Kottamasu; G. Preston; D. Treloar

1988-01-01

327

Unilateral pulmonary edema and acute rheumatic fever  

Microsoft Academic Search

Although the diagnostic criteria for acute rheumatic fever (ARF) are well known, a high index of suspicion is necessary in\\u000a order to assure timely diagnosis and appropriate treatment. We present a case of an 8-year-old child who presented with unilateral\\u000a pulmonary edema secondary to acute mitral insufficiency due to ARF. ARF should be considered in the differential diagnosis\\u000a of unilateral

John S. Giuliano Jr; Priya Sekar; Catherine L. Dent; William L. Border; Russel Hirsch; Peter B. Manning; Derek S. Wheeler

2008-01-01

328

High altitude pulmonary edema in mountain climbers.  

PubMed

Every year thousands of ski, trekking or climbing fans travel to the mountains where they stay at the altitude of more than 2500-3000m above sea level or climb mountain peaks, often exceeding 7000-8000m. High mountain climbers are at a serious risk from the effects of adverse environmental conditions prevailing at higher elevations. They may experience health problems resulting from hypotension, hypoxia or exposure to low temperatures; the severity of those conditions is largely dependent on elevation, time of exposure as well as the rate of ascent and descent. A disease which poses a direct threat to the lives of mountain climbers is high altitude pulmonary edema (HAPE). It is a non-cardiogenic pulmonary edema which typically occurs in rapidly climbing unacclimatized lowlanders usually within 2-4 days of ascent above 2500-3000m. It is the most common cause of death resulting from the exposure to high altitude. The risk of HAPE rises with increased altitude and faster ascent. HAPE incidence ranges from an estimated 0.01% to 15.5%. Climbers with a previous history of HAPE, who ascent rapidly above 4500m have a 60% chance of illness recurrence. The aim of this article was to present the relevant details concerning epidemiology, pathophysiology, clinical symptoms, prevention, and treatment of high altitude pulmonary edema among climbers in the mountain environment. PMID:25291181

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

2014-10-01

329

Malignant edema in postpartum dairy cattle.  

PubMed

Five cases of postparturient vulvovaginitis and metritis in cattle caused by Clostridium septicum (malignant edema) are described in the current report. The diagnosis was established based on detection of C. septicum by culture and fluorescent antibody test. All animals were Holsteins, and 4 were primiparous (the parity of 1 animal was not reported). All animals developed clinical signs 1-3 days after calving, consisting of swelling of perineal and perivulvar areas, fever, and depression. Perineal, perivulvar, and perivaginal gelatinous and often hemorrhagic edema was consistently observed on gross examination. Longitudinal vulvar, vaginal, cervical, and uterine body tears, covered by fibrinous exudates, were also present. Microscopically, vulvar, vaginal, and uterine mucosae were multifocally necrotic and ulcerated. Large Gram-positive rods, some with subterminal spores, were present within the edematous subcutaneous and submucosal tissues. Clostridium septicum was demonstrated by culture and/or fluorescent antibody test in tissues of most animals. These cases of malignant edema were considered to be produced by C. septicum and predisposed by the trauma occurring during parturition. PMID:19901305

Odani, Jenee S; Blanchard, Patricia C; Adaska, John M; Moeller, Robert B; Uzal, Francisco A

2009-11-01

330

Structure-based redesign of an edema toxin inhibitor  

PubMed Central

Edema Factor toxin (EF) of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3?,5?-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-Oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 ?g/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin-(ET) catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria. PMID:22154558

Chen, Deliang; Ma, Lili; Kanalas, John J.; Gao, Jian; Pawlik, Jennifer; Jimenez, Maria Estrella; Walter, Mary A.; Peterson, Johnny W.; Gilbertson, Scott R.; Schein, Catherine H.

2011-01-01

331

Use of Electrical Impedance Tomography to Monitor Regional Cerebral Edema during Clinical Dehydration Treatment  

PubMed Central

Objective Variations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content. Design a prospective study. Setting In this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank. Patients 23 patients with brain edema. Interventions The patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes. Measurement and Main Results Overall impedance across the brain increased significantly before and after mannitol dehydration treatment (p?=?0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment. Conclusions EIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients. PMID:25474474

Hu, Shi-Jie; Li, Xia; Xu, Can-Hua; Wang, Bing; Yang, Bin; Tang, Meng-Xing; Dong, Xiu-Zhen; Fei, Zhou; Shi, Xue-Tao

2014-01-01

332

Cardiac MRI of Edema in Acute Myocardial Infarction using Cine Balanced SSFP: A Translational Study  

PubMed Central

Objective To investigate the capabilities of balanced steady-state-free-precession (bSSFP) MRI as a novel cine imaging approach for characterizing myocardial edema in animals and patients following reperfused myocardial infarction. Background Current MRI methods require two separate scans for assessment of myocardial edema and cardiac function. Methods Mini-pigs (n=13) with experimentally induced reperfused myocardial infarction and patients with reperfused STEMI (n=26) underwent MR scans on days 2–4 post reperfusion. Cine bSSFP, T2-STIR, and late-gadolinium enhancement (LGE) were performed at 1.5T. Cine bSSFP and T2-STIR images were acquired with body coil to mitigate surface coil bias. Signal, contrast and the area of edema were compared. Additional patients (n=10) were analyzed for the effect of microvascular obstruction on bSSFP. A receiver-operator-characteristic analysis was performed to assess the accuracy of edema detection. Results An area of hyperintense bSSFP signal consistent with edema was observed in the infarction zone (contrast-to-noise ratio (CNR) 37±13) in all animals and correlated well with the area of LGE (R=0.83, p<0.01). In all patients, T2-STIR and bSSFP images showed regional hyperintensity in the infarction zone. Normalized CNR were not different between T2-STIR and bSSFP. On a slice-basis, the volumes of hyperintensity on T2-STIR and bSSFP images correlated well (R=0.86, p<0.001), and their means were not different. When compared with T2-STIR, bSSFP was positive for edema in 25/26 patients (sensitivity of 96%) and was negative in all controls (specificity 100%). All patients with MVO showed a significant reduction of signal in the subendocardial infarction zone, compared to infarcted epicardial tissue without MVO (p<0.05). Conclusion Myocardial edema from STEMI can be detected using cine bSSFP imaging with image contrast similar to T2-STIR. This new imaging approach allows for evaluating cardiac function and edema simultaneously, thereby reducing patient scan time and increasing efficiency. Further work is necessary to optimize edema contrast in bSSFP images. PMID:22172783

Kumar, Andreas; Beohar, Nirat; Arumana, Jain Mangalathu; Larose, Eric; Li, Debiao; Friedrich, Matthias G; Dharmakumar, Rohan

2012-01-01

333

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

PubMed Central

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

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

2013-01-01

334

Retrograde, Transneuronal Spread of Pseudorabies Virus in Defined Neuronal Circuitry of the Rat Brain Is Facilitated by gE Mutations That Reduce Virulence  

PubMed Central

The pseudorabies virus (PRV) gE gene encodes a multifunctional membrane protein found in infected cell membranes and in the virion envelope. Deletion of the gE gene results in marked attenuation of the virus in almost every animal species tested that is permissive for PRV. A common inference is that gE mutants are less virulent because they have reduced ability to spread from cell to cell; e.g., gE mutants infect fewer cells and, accordingly, animals live longer. In this report, we demonstrate that this inference does not hold in a rat experimental model for virus invasion of the brain. We find that animals infected with gE mutants live longer despite extensive retrograde, transneuronal spread of virus in the rat brain. In this model of brain infection, virus is injected into the stomach musculature and virions spread to the brain in long axons of brain stem neurons that give rise to the tenth cranial nerve (the vagus). The infection then spreads from neuron to neuron in well-defined, and physically separated, areas of the brain involved in autonomic regulation of the viscera. We examined the progression of infection of five PRV strains in this circuitry: the wild-type PRV-Becker strain, the attenuated PRV-Bartha vaccine strain, and three gE mutants isogenic with the PRV-Becker strain. By 60 to 67 h after infection, all PRV-Becker-infected animals were dead. Analysis of Becker-infected rats killed prior to virus-induced death demonstrated that the virus had established an infection only in the primary vagal neurons connected directly to the stomach and synaptically linked neurons in the immediate vicinity of the caudal brain stem. There was little spread to other neurons in the vagus circuitry. In contrast, rats infected with PRV-Bartha or PRV-Becker gE mutants survived to at least 96 h and exhibited few overt signs of disease. Despite this long survival and the lack of symptoms, brains of animals sacrificed at this time revealed extensive transsynaptic infection not only of the brain stem but also of areas of the forebrain synaptically linked to neurons in the brain stem. This finding provides evidence that the gE protein plays a role in promoting symptoms of infection and death in animals that is independent of neuron-to-neuron spread during brain infection. When this early virulence function is not active, animals live longer, resulting in more extensive spread of virus in the brain. PMID:10196333

Yang, M.; Card, J. P.; Tirabassi, R. S.; Miselis, R. R.; Enquist, L. W.

1999-01-01

335

Retrograde, transneuronal spread of pseudorabies virus in defined neuronal circuitry of the rat brain is facilitated by gE mutations that reduce virulence.  

PubMed

The pseudorabies virus (PRV) gE gene encodes a multifunctional membrane protein found in infected cell membranes and in the virion envelope. Deletion of the gE gene results in marked attenuation of the virus in almost every animal species tested that is permissive for PRV. A common inference is that gE mutants are less virulent because they have reduced ability to spread from cell to cell; e.g., gE mutants infect fewer cells and, accordingly, animals live longer. In this report, we demonstrate that this inference does not hold in a rat experimental model for virus invasion of the brain. We find that animals infected with gE mutants live longer despite extensive retrograde, transneuronal spread of virus in the rat brain. In this model of brain infection, virus is injected into the stomach musculature and virions spread to the brain in long axons of brain stem neurons that give rise to the tenth cranial nerve (the vagus). The infection then spreads from neuron to neuron in well-defined, and physically separated, areas of the brain involved in autonomic regulation of the viscera. We examined the progression of infection of five PRV strains in this circuitry: the wild-type PRV-Becker strain, the attenuated PRV-Bartha vaccine strain, and three gE mutants isogenic with the PRV-Becker strain. By 60 to 67 h after infection, all PRV-Becker-infected animals were dead. Analysis of Becker-infected rats killed prior to virus-induced death demonstrated that the virus had established an infection only in the primary vagal neurons connected directly to the stomach and synaptically linked neurons in the immediate vicinity of the caudal brain stem. There was little spread to other neurons in the vagus circuitry. In contrast, rats infected with PRV-Bartha or PRV-Becker gE mutants survived to at least 96 h and exhibited few overt signs of disease. Despite this long survival and the lack of symptoms, brains of animals sacrificed at this time revealed extensive transsynaptic infection not only of the brain stem but also of areas of the forebrain synaptically linked to neurons in the brain stem. This finding provides evidence that the gE protein plays a role in promoting symptoms of infection and death in animals that is independent of neuron-to-neuron spread during brain infection. When this early virulence function is not active, animals live longer, resulting in more extensive spread of virus in the brain. PMID:10196333

Yang, M; Card, J P; Tirabassi, R S; Miselis, R R; Enquist, L W

1999-05-01

336

The use of manual edema mobilization for the reduction of persistent edema in the upper limb.  

PubMed

Management of persistent edema with the common treatment methods reported in the literature is not always successful. Manual edema mobilization (MEM) is a relatively new treatment regimen derived from established European and Australian lymphedema reduction regimens. It includes the use of exercises, light skin-tractioning massage techniques following the lymphatic pathways, and the use of low-compression garments. The typical patient who may benefit from the use of MEM has a presumed healthy lymphatic system, is an active participant, and performs some of the techniques independently between therapy sessions. This case report describes the use of MEM on a patient with multiple trauma, which resulted in a significant reduction--78%--of the persistent edema in the affected upper limb. A theoretic rationale is offered for each MEM technique. PMID:11762730

Howard, S B; Krishnagiri, S

2001-01-01

337

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice  

PubMed Central

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

338

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

SciTech Connect

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

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

1985-07-01

339

Reduced early hypoxic/ischemic brain damage is associated with increased GLT-1 levels in mice expressing mutant (P301L) human tau  

PubMed Central

Mutations in tau proteins are associated with a group of neurodegenerative diseases, termed tauopathies. To investigate whether over-expressing human tau with P301L mutation also affects stroke-induced brain damage, we performed hypoxia/ischemia (H/I) in young adult P301L tau transgenic mice. Surprisingly, brain infarct volume was significantly smaller in transgenic mice compared to wild-type mice 24 h after H/I induction. TUNEL staining also revealed less brain apoptosis in transgenic mice following H/I. H/I resulted in a significant increase in tau fragments generated by caspase activation and a marked decrease in tau phosphorylation at residue T231 in cortex of wild-type but not transgenic mice. Activation of calpain and caspase-3 following H/I was also reduced in transgenic compared to wild-type mice, as reflected by lower levels of the specific spectrin breakdown products generated by calpain or caspase-3. Finally, basal levels of the glial glutamate transporter, GLT-1, were higher in brains of transgenic as compared to wild-type mice. These results support the idea that enhanced levels of GLT-1 in transgenic mice are responsible for reducing H/I-induced brain damage by decreasing extracellular glutamate accumulation and subsequent calpain and caspase activation. PMID:18992725

Liao, Guanghong; Zhou, Miou; Cheung, Simon; Galeano, James; Nguyen, Nam; Baudry, Michel; Bi, Xiaoning

2009-01-01

340

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

PubMed Central

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

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

2014-01-01

341

New insights of aquaporin 5 in the pathogenesis of high altitude pulmonary edema  

PubMed Central

Background High altitude pulmonary edema (HAPE) affects individuals and is characterized by alveolar flooding with protein-rich edema as a consequence of blood-gas barrier disruption. In this study, we hypothesized that aquaporin 5 (AQP5) which is one kind of water channels may play a role in preservation of alveolar epithelial barrier integrity in high altitude pulmonary edema (HAPE). Methods Therefore, we established a model in Wildtype mice and AQP5 ?/? mice were assingned to normoxic rest (NR), hypoxic rest (HR) and hypoxic exercise (HE) group. Mice were produced by training to walk at treadmill for exercising and chamber pressure was reduced to simulate climbing an altitude of 5000 m for 48 hours. Studies using BAL in HAPE mice to demonstrated that edema is caused leakage of albumin proteins and red cells across the alveolarcapillary barrier in the absence of any evidence of inflammation. Results In this study, the Lung wet/dry weight ratio and broncholalveolar lavage protein concentrations were slightly increased in HE AQP5 ?/? mice compared to wildtype mice. And histologic evidence of hemorrhagic pulmonary edema was distinctly shown in HE group. The lung Evan’s blue permeability of HE group was showed slightly increased compare to the wildtype groups, and HR group was showed a medium situation from normal to HAPE development compared with NR and HE group. Conclusions Deletion of AQP5 slightly increased lung edema and lung injury compared to wildtype mice during HAPE development, which suggested that the AQP5 plays an important role in HAPE formation induced by high altitude simulation. PMID:24274330

2013-01-01

342

The inhibitory effect of S-nitrosoglutathione on blood-brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke.  

PubMed

The hallmark of stroke injury is endothelial dysfunction leading to blood-brain barrier (BBB) leakage and edema. Among the causative factors of BBB disruption are accelerating peroxynitrite formation and the resultant decreased bioavailability of nitric oxide (NO). S-nitrosoglutathione (GSNO), an S-nitrosylating agent, was found not only to reduce the levels of peroxynitrite but also to protect the integrity of BBB in a rat model of cerebral ischemia and reperfusion (IR). A treatment with GSNO (3 ?mol/kg) after IR reduced 3-nitrotyrosine levels in and around vessels and maintained NO levels in brain. This mechanism protected endothelial function by reducing BBB leakage, increasing the expression of Zonula occludens-1 (ZO-1), decreasing edema, and reducing the expression of matrix metalloproteinase-9 and E-selectin in the neurovascular unit. An administration of the peroxynitrite-forming agent 3-morpholino sydnonimine (3 ?mol/kg) at reperfusion increased BBB leakage and decreased the expression of ZO-1, supporting the involvement of peroxynitrite in BBB disruption and edema. Mechanistically, the endothelium-protecting action of GSNO was invoked by reducing the activity of nuclear factor kappa B and increasing the expression of S-nitrosylated proteins. Taken together, the results support the ability of GSNO to improve endothelial function by reducing nitroxidative stress in stroke. PMID:23050646

Khan, Mushfiquddin; Dhammu, Tajinder S; Sakakima, Harutoshi; Shunmugavel, Anadakumar; Gilg, Anne G; Singh, Avtar K; Singh, Inderjit

2012-11-01

343

[Pharmacological treatment for diabetic macular edema].  

PubMed

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

Fukumoto, Masanori; Ikeda, Tsunehiko

2015-03-01

344

Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats  

PubMed Central

Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of 15NH4+ into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of 15NH4+ into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of 15NH4+ into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of 15N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia. PMID:24346692

Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

2014-01-01

345

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

PubMed Central

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

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

2014-01-01

346

Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats  

PubMed Central

Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

2012-01-01

347

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia  

PubMed Central

Opioid conjugate vaccines have shown promise in attenuating the behavioral effects of heroin or morphine in animals. The goal of this study was to extend this approach to oxycodone (OXY), a commonly abused prescription opioid. Haptens were generated by adding tetraglycine (Gly)4 or hemisuccinate (HS) linkers at the 6-position of OXY. Immunization of rats with OXY(Gly)4 conjugated to the carrier proteins bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) produced high-titer antibodies to OXY and its metabolite oxymorphone with substantially lower affinities for other structurally related opioid agonists and antagonists. There was no measurable binding of antibody by the (Gly)4 linker alone or off-target opioids methadone and buprenorphine. OXY(HS) conjugates were less immunogenic despite achieving protein haptenation ratios comparable to OXY(Gly)4-BSA. In rats given a single intravenous dose of OXY, immunization with OXY(Gly)4-KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain. Vaccine efficacy correlated with serum antibody titers, and it was greatest in rats given the lowest OXY dose (0.05 mg/kg) but was significant even after a larger OXY dose (0.5 mg/kg), equivalent to the high end of the therapeutic range in humans. These effects of OXY(Gly)4-KLH on drug disposition were comparable to those of nicotine or cocaine vaccines that are in clinical trials as addiction treatments. Immunization with OXY(Gly)4-KLH also reduced OXY analgesia in a thermal nociception test. These data support further study of vaccination with the OXY(Gly)4-KLH immunogen as a potential treatment option for OXY abuse or addiction. PMID:22262924

Le Naour, M.; Harmon, T. M.; Tucker, A. M.; Portoghese, P. S.; Pentel, P. R.

2012-01-01

348

Vascular endothelial growth factors in pulmonary edema: an update  

Microsoft Academic Search

Pulmonary edema is a life-threatening complication of critical illness. Identification of the underlying mechanisms of pulmonary\\u000a edema is a prerequisite for the development of adequate treatment. The initial description of fluid transportation across\\u000a capillaries (Starling’s law) while of critical importance, did not provide full insight into the underlying pathophysiology\\u000a of vascular leakage. Pulmonary edema can be differentiated into two distinct

Ioanna Kosmidou; Dimitrios Karmpaliotis; Ajay J. Kirtane; Hal V. Barron; C. Michael Gibson

2008-01-01

349

Pulmonary Edema: Which Role for Echocardiography in the Diagnostic Workup?  

Microsoft Academic Search

\\u000a In the presence of pulmonary edema, the distinction between hydrostatic (often cardiogenic) and permeability (acute respiratory\\u000a distress syndrome) edema is crucial in the hypoxemic critically-ill patient. Importantly, the absence of relevant left ventricular\\u000a (LV) systolic dysfunction fails to rule outa hydrostatic pulmonary edema (e.g., acute valvular regurgitation, volume overload,\\u000a severe diastolic dysfunction, mitral stenosis) and, conversely, acuterespiratory distress syndrome (ARDS)

Philippe Vignon; Frances Colreavy; Michel Slama

350

Periorbital Edema Secondary to Positive Airway Pressure Therapy  

PubMed Central

Two patients developed bilateral, periorbital edema after initiating positive airway pressure (PAP) therapy with a full face mask. The periorbital edema was more pronounced in the morning and would dissipate throughout the day. This phenomenon seemed to be correlated with the direct pressure of the full face mask, which may have impaired lymphatic and venous drainage. To test this hypothesis, each patient was changed to a nasal pillow interface with subsequent improvement in the periorbital edema.

Dandekar, F.; Camacho, M.; Valerio, J.; Ruoff, C.

2015-01-01

351

The Curious Question of Exercise-Induced Pulmonary Edema  

PubMed Central

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

2011-01-01

352

Licorice induced hypokalemia, edema, and thrombocytopenia.  

PubMed

Licorice originates from the root of Glycyrrhiza glabra, which has a herbal ingredient, glycyrrhizic acid, and has a mineralocorticoid-like effect. Chronic intake of licorice induces a syndrome similar to that found in primary hyperaldosteronism. Excessive intake of licorice may cause a hypermineralocorticoidism-like syndrome characterized by sodium and water retention, hypertension, hypokalemia, metabolic alkalosis, low-renin activity, and hypoaldosteronism. In this case report, an association of hypokalemia, edema, and thrombocytopenia that is developed due to the excessive intake of licorice is presented. There are case reports in the literature, which suggest that toxicity findings may emerge with hyperaldosteronism-like manifestations such as hypokalemia, edema, and hypertension. However, any knowledge of thrombocytopenia as a resultant was not encountered among these reported toxic effects. Our case is important because it shows that the excessive intake of licorice may cause a toxic effect in the form of thrombocytopenia. This report is the first presented case to show thrombocytopenia due to licorice syrup consumption. PMID:22653692

Celik, M M; Karakus, A; Zeren, C; Demir, M; Bayarogullari, H; Duru, M; Al, M

2012-12-01

353

New Compton densitometer for measuring pulmonary edema  

SciTech Connect

Pulmonary edema is the pathological increase of extravascular lung water found most often in patients with congestive heart failure and other critically ill patients who suffer from intravenous fluid overload. A non-invasive lung density monitor that is accurate, easily portable, safe and inexpensive is needed for clinical evaluation of pulmonary edema. Other researchers who have employed Compton scattering techniques generally used systems of extended size and detectors with poor energy resolution. This has resulted in significant systematic biases from multiply-scattered photons and larger errors in counting statistics at a given radiation dose to the patient. We are proposing a patented approach in which only backscattered photons are measured with a high-resolution HPGe detector in a compact system geometry. By proper design and a unique data extraction scheme, effects of the variable chest wall on lung density measurements are minimized. Preliminary test results indicate that with a radioactive source of under 30 GBq, it should be possible to make an accurate lung density measurement in one minute, with a risk of radiation exposure to the patient a thousand times smaller than that from a typical chest x-ray. The ability to make safe, frequent lung density measurements could be very helpful for monitoring the course of P.E. at the hospital bedside or outpatient clinics, and for evaluating the efficacy of therapy in clinical research. 6 refs., 5 figs.

Loo, B.W.; Goulding, F.S.; Simon, D.S.

1985-10-01

354

The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of alpha-methyl-L-tryptophan: an autoradiographic study.  

PubMed

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis. PMID:11900855

Tohyama, Yoshihiro; Takahashi, Sho; Merid, Maraki Fikre; Watanabe, Arata; Diksic, Mirko

2002-06-01

355

The murine version of BAN2401 (mAb158) selectively reduces amyloid-? protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice.  

PubMed

Amyloid-? (A?) immunotherapy for Alzheimer's disease (AD) has good preclinical support from transgenic mouse models and clinical data suggesting that a long-term treatment effect is possible. Soluble A? protofibrils have been shown to exhibit neurotoxicity in vitro and in vivo, and constitute an attractive target for immunotherapy. Here, we demonstrate that the humanized antibody BAN2401 and its murine version mAb158 exhibit a strong binding preference for A? protofibrils over A? monomers. Further, we confirm the presence of the target by showing that both antibodies efficiently immunoprecipitate soluble A? aggregates in human AD brain extracts. mAb158 reached the brain and reduced the brain protofibril levels by 42% in an exposure-dependent manner both after long-term and short-term treatment in tg-ArcSwe mice. Notably, a 53% reduction of protofibrils/oligomers in cerebrospinal fluid (CSF) that correlated with reduced brain protofibril levels was observed after long-term treatment, suggesting that CSF protofibrils/oligomers could be used as a potential biomarker. No change in native monomeric A?42 could be observed in brain TBS extracts after mAb158-treatment in tg-ArcSwe mice. By confirming the specific ability of mAb158 to selectively bind and reduce soluble A? protofibrils, with minimal binding to A? monomers, we provide further support in favor of its position as an attractive new candidate for AD immunotherapy. BAN2401 has undergone full phase 1 development, and available data indicate a favorable safety profile in AD patients. PMID:25096615

Tucker, Stina; Möller, Christer; Tegerstedt, Karin; Lord, Anna; Laudon, Hanna; Sjödahl, Johan; Söderberg, Linda; Spens, Erika; Sahlin, Charlotte; Waara, Erik Rollman; Satlin, Andrew; Gellerfors, Pär; Osswald, Gunilla; Lannfelt, Lars

2015-01-01

356

Hyperbaric oxygenation reduces overexpression of c-Fos and oxidative stress in the brain stem of experimental endotoxemic rats  

Microsoft Academic Search

Objective  Septic encephalopathy is associated with an increased mortality rate in septic patients. We have previously shown that a peripheral\\u000a lipopolysaccharide (LPS) injection induces neuronal activation in the brain-stem nuclei of rats. Nitric oxide (NO) and superoxide\\u000a are involved in LPS-induced brain damage. Hyperbaric oxygenation (HBO) provides protective effects against systemic oxidative\\u000a stress and mortality in animals with septic shock. We examined

Hui-Ching Lin; Fang-Jung Wan

2008-01-01

357

Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration.  

PubMed

The clinical development of neuropeptides has been limited by a combination of the short plasma half-life of these drugs and their ultimate failure to permeate the blood brain barrier. Peptide nanofibres have been used to deliver peptides across the blood brain barrier and in this work we demonstrate that the polymer coating of peptide nanofibres further enhances peptide delivery to the brain via the intravenous route. Leucine(5)-enkephalin (LENK) nanofibres formed from the LENK ester prodrug - tyrosinyl(1)palmitate-leucine(5)-enkephalin (TPLENK) were coated with the polymer - N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) and injected intravenously. Peptide brain delivery was enhanced because the GCPQ coating on the peptide prodrug nanofibres, specifically enables the peptide prodrug to escape liver uptake, avoid enzymatic degradation to non-active sequences and thus enjoy a longer plasma half life. Plasma half-life is increased 520%, liver AUC0-4 decreased by 54% and brain AUC0-4 increased by 47% as a result of the GCPQ coating. The increased brain levels of the GCPQ coated peptide prodrug nanofibres result in the pharmacological activity of the parent drug (LENK) being significantly increased. LENK itself is inactive on intravenous injection. PMID:25449808

Lalatsa, A; Schätzlein, A G; Garrett, N L; Moger, J; Briggs, Michael; Godfrey, Lisa; Iannitelli, Antonio; Freeman, Jay; Uchegbu, I F

2015-01-10

358

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

PubMed

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

Bierbower, Sonya M; Choveau, Frank S; Lechleiter, James D; Shapiro, Mark S

2015-02-01

359

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

PubMed

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

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

2014-03-01

360

Noncardiac Pulmonary Edema induced by Sitagliptin Treatment  

PubMed Central

A 74-year-old male patient with type 2 diabetes mellitus admitted to the emergency department with the complaints of progressive breathlessness, dry cough, and swollen lower extremities. Our patient had type 2 diabetes mellitus and hypertension for 3 years. His HbA1c was not within the target range so sitagliptin was added to on-going therapy. After 1 week of starting sitagliptin therapy, even though the patient had not heart failure he applied to the emergency department with a complaint of dyspnea. The cardiovascular safety and efficacy of many anti-hyperglycemic agents such as sitagliptin, saxagliptin are unclear. Our case has shown that dipeptidyl peptidase 4 inhibitors may cause pulmonary edema. Hence, it should be used with cautious, especially in patients with heart failure. PMID:25657966

Belice, Tahir; Yuce, Suleyman; Kizilkaya, Bayram; Kurt, Aysel; Cure, Erkan

2014-01-01

361

Noncardiac Pulmonary Edema induced by Sitagliptin Treatment.  

PubMed

A 74-year-old male patient with type 2 diabetes mellitus admitted to the emergency department with the complaints of progressive breathlessness, dry cough, and swollen lower extremities. Our patient had type 2 diabetes mellitus and hypertension for 3 years. His HbA1c was not within the target range so sitagliptin was added to on-going therapy. After 1 week of starting sitagliptin therapy, even though the patient had not heart failure he applied to the emergency department with a complaint of dyspnea. The cardiovascular safety and efficacy of many anti-hyperglycemic agents such as sitagliptin, saxagliptin are unclear. Our case has shown that dipeptidyl peptidase 4 inhibitors may cause pulmonary edema. Hence, it should be used with cautious, especially in patients with heart failure. PMID:25657966

Belice, Tahir; Yuce, Suleyman; Kizilkaya, Bayram; Kurt, Aysel; Cure, Erkan

2014-01-01

362

Elephantoid eyelid edema associated with continuous positive airway pressure treatment.  

PubMed

A man with rosacea developed bilateral eyelid edema from wearing a continuous positive airway pressure nasal mask daily. The edema was refractory to steroid, diuretics, and lymphatic drainage massage. The effect may be related to cumulative venous congestion and lymphostasis due to the continuous positive airway pressure treatment. PMID:23128530

Chiam, Patrick J T; Hubbard, Alan D

2013-01-01

363

Fumonisin-induced pulmonary edema and hydrothorax in swine  

Microsoft Academic Search

Pulmonary edema and hydrothorax were observed in mature swine that died approximately 5 days after consuming corn screenings. These postmortem observations were reproduced in younger pigs that died within 1 week when fed the corn screenings under experimental conditions. Additionally, pulmonary edema and hydrothorax were induced in a pig that died after receiving 4 daily intravenous injections of fumonisin B1,

Bill M. Colvin; Lenn R. Harrison

1992-01-01

364

Orbital Fat Edema in Anorexia Nervosa: A Reversible Finding  

Microsoft Academic Search

Summary: Orbital fat edema was found in a patient with long- standing severe anorexia nervosa. The changes disappeared af- ter the patient gained weight. The underlying mechanism re- mains unexplained, but the changes most likely coincide with the disappearance of fat tissue and the appearance of edema follow- ing disturbance of the electrolyte\\/fluid balance. Cranial computed tomography (CT) and magnetic

Philippe Demaerel; Maria Casteels-Van Daele; Sofie De Vuysere; Guy Wilms; Albert L. Baert

365

Non Invasive Mechanical Ventilation in cardiogenic pulmonary edema  

Microsoft Academic Search

1. PHYSIOPATHOLOGY OF CARDIOGENIC PULMONARY EDEMA Acute heart failure is defined as the rapid onset of symptoms and signs secondary to abnormal cardiac function and it may occur with or without previous cardiac disease. The patient with AHF may present with one of several distinct clinical conditions like pulmonary edema, hypertensive acute heart failure, cardiogenic shock, high output failure, and

Stavros Tryfon

366

Targeted photocoagulation of peripheral ischemia to treat rebound edema  

PubMed Central

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

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

2015-01-01

367

Massive vulvar edema in 2 prepartum dairy cows  

PubMed Central

Two late gestation Holstein cows about to begin the third lactation developed massive vulvar edema. These were the only affected animals in the herd of 500 milking cows. The vulvar edema spontaneously regressed postpartum for both cows. Massive vulvar swelling is seldom observed in dairy cows in advanced pregnancy and is not described in the literature. PMID:24790232

Cheong, Soon Hon; Gilbert, Robert O.

2014-01-01

368

Excellent Tolerance to Cilnidipine in Hypertensives with Amlodipine - Induced Edema  

PubMed Central

Background: Ankle edema is a common adverse effect of amlodipine, an L-type calcium channel blocker (CCB). Cilnidipine is a newer L/N-type CCB, approved for treatment of essential hypertension. Aim: This study was designed to determine whether cilnidipine can produce resolution of amlodipine-induced edema while maintaining adequate control of hypertension. Materials and Methods: A prospective study was performed on 27 patients with essential hypertension with amlodipine-induced edema. Concomitant nephropathy, cardiac failure, hepatic cirrhosis, or other causes of edema, and secondary hypertension were excluded by appropriate tests. Amlodipine therapy was substituted in all the cases with an efficacy-equivalent dose of cilnidipine. Clinical assessment of ankle edema and measurement of bilateral ankle circumference, body weight, blood pressure, and pulse rate were performed at onset of the study and after 4 weeks of cilnidipine therapy. Results: At completion of the study, edema had resolved in all the patients. There was a significant decrease in bilateral ankle circumference and body weight (P < 0.001). There was no significant change in mean arterial blood pressure and pulse rate. Conclusions: Therapy with cilnidipine resulted in complete resolution of amlodipine-induced edema in all the cases without significant worsening of hypertension or tachycardia. Cilnidipine is an acceptable alternative antihypertensive for patients with amlodipine-induced edema. PMID:23378956

Shetty, Ranjan; Vivek, G; Naha, Kushal; Tumkur, Anil; Raj, Abhinav; Bairy, K L

2013-01-01

369

Cystoid macular edema associated with topical echothiophate iodide.  

PubMed

We report the case of a patient with visual loss and cystoid macular edema that was associated with the topical use of echothiophate iodide. After cessation of the drops, the cystoid macular edema nearly disappeared, and vision returned to normal. PMID:8129329

Halperin, L S; Goldman, H B

1993-12-01

370

Massive vulvar edema in 2 prepartum dairy cows.  

PubMed

Two late gestation Holstein cows about to begin the third lactation developed massive vulvar edema. These were the only affected animals in the herd of 500 milking cows. The vulvar edema spontaneously regressed postpartum for both cows. Massive vulvar swelling is seldom observed in dairy cows in advanced pregnancy and is not described in the literature. PMID:24790232

Cheong, Soon Hon; Gilbert, Robert O

2014-05-01

371

Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies  

PubMed Central

Background Structural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done. Methods In global and regional meta-analyses of 9 voxel-based morphometry (VBM) studies, with a total of 228 eating disorder participants (currently ill with anorexia nervosa), and 240 age-matched healthy controls, we compare brain volumes using global and regional analyses. Results Anorexia nervosa (AN) patients have global reductions in gray (effect size?=??0.66) and white matter (effect size?=??0.74) and increased cerebrospinal fluid (effect size?=?0.98) and have regional decreases in left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate, and no significant increases. No significant difference in hemispheric lateralization was found. Conclusions Global and regional meta-analyses suggest that excessive restrained eating as found in those with anorexia nervosa coincides with structural brain changes analogous to clinical symptoms. PMID:23570420

2013-01-01

372

Smoke aldehyde component influences pulmonary edema  

SciTech Connect

The pulmonary edema of smoke inhalation is caused by the toxins of smoke and not the heat. We investigated the potential of smoke consisting of carbon in combination with either acrolein or formaldehyde (both common components of smoke) to cause pulmonary edema in anesthetized sheep. Seven animals received acrolein smoke, seven animals received a low-dose formaldehyde smoke, and five animals received a high-dose formaldehyde smoke. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were not affected by smoke in any group. Peak airway pressure increased after acrolein (14 +/- 1 to 21 +/- 2 mmHg; P less than 0.05) and after low- and high-dose formaldehyde (14 +/- 1 to 21 +/- 1 and 20 +/- 1 mmHg, respectively; both P less than 0.05). The partial pressure of O2 in arterial blood fell sharply after acrolein (219 +/- 29 to 86 +/- 9 (SE) Torr; P less than 0.05) but not after formaldehyde. Only acrolein resulted in a rise in lung lymph flow (6.5 +/- 2.2 to 17.9 +/- 2.6 ml/h; P less than 0.05). Lung lymph-to-plasma protein ratio was unchanged for all three groups, but clearance of lymph protein was increased after acrolein. After acrolein, the blood-free extravascular lung water-to-lung dry weight ratio was elevated (P less than 0.05) compared with both low- and high-dose formaldehyde groups (4.8 +/- 0.4 to 3.3 +/- 0.2 and 3.6 +/- 0.2, respectively). Lymph clearance (ng/h) of thromboxane B2, leukotriene B4, and the sulfidopeptide leukotrienes was elevated after acrolein but not formaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

Hales, C.A.; Musto, S.W.; Janssens, S.; Jung, W.; Quinn, D.A.; Witten, M. (Department of Medicine (Pulmonary/Critical Care Unit), Massachusetts General Hospital, Boston (United States))

1992-02-01

373

Oxygen-deficient metabolism and corneal edema  

PubMed Central

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

Leung, B.K.; Bonanno, J.A.; Radke, C.J.

2014-01-01

374

Serous retinal detachment and cystoid macular edema in a patient with wyburn-mason syndrome.  

PubMed

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

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

2015-03-01

375

Deficiency of complement receptors CR2/CR1 in Cr2-/- mice reduces the extent of secondary brain damage after closed head injury  

PubMed Central

Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2 -/- mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2 -/- mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2 -/- mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2 -/- genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2 -/- mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2 -/- had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury. PMID:24885042

2014-01-01

376

Protective actions of PJ34, a poly(ADP-ribose)polymerase inhibitor, on the blood-brain barrier after traumatic brain injury in mice.  

PubMed

Poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays an important role in traumatic brain injury (TBI). The objective of this study was to investigate whether PARP activation participated in the blood-brain barrier (BBB) disruption and edema formation in a mouse model of controlled cortical impact (CCI). N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (10mg/kg), a selective PARP inhibitor, was administered intraperitoneally at 5min and 8h after experimental CCI. After 6h and 24h of CCI, the permeability of the cortical BBB was determined after Evans Blue administration. The water content of the brain was also measured. Treatment with PJ34 markedly attenuated the permeability of the BBB and decreased the brain edema at 6h and 24h after CCI. Our data showed the up-regulation of nuclear factor-?B in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by PJ34. Moreover, PJ34 significantly lessened the activities of myeloperoxidase and the levels of matrix metalloproteinase-9, enhanced the levels of occludin, laminin, collagen IV and integrin ?1, reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death. These data suggest the protective effects of PJ34 on BBB integrity and cell death during acute TBI. PMID:25668593

Tao, X; Chen, X; Hao, S; Hou, Z; Lu, T; Sun, M; Liu, B

2015-04-16

377

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

ERIC Educational Resources Information Center

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

Furman, Orit; Mendelsohn, Avi; Dudai, Yadin

2012-01-01

378

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

EPA Science Inventory

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

379

Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism  

PubMed Central

Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. PMID:24451134

Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

2014-01-01

380

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

SciTech Connect

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

Zielinska, Elzbieta [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Kuc, Damian [Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland); Zgrajka, Wojciech [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Turski, Waldemar A. [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland); Dekundy, Andrzej [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland)], E-mail: andrzej.dekundy@merz.de

2009-10-15

381

Comparison of diffusion-weighted with T2-weighted imaging for detection of edema in acute myocardial infarction  

PubMed Central

Background Recent studies, performed with the use of a commercially available diffusion weighted imaging (DWI) sequence, showed that they are sensitive to the increase of water content in the myocardium and may be used as an alternative to the standard T2-weighted sequences. The aim of this study was to compare two methods of myocardial edema imaging: DWI and T2-TIRM. Methods The study included 91 acute and post STEMI patients. We applied a qualitative and quantitative image analysis. The qualitative analysis consisted of evaluation of the quality of blood suppression, presence of artifacts and occurrence of high signal (edema) areas. On the basis of edema detection in AMI and control (post STEMI) group, the sensitivity and specificity of TIRM and DWI were determined. Two contrast to noise ratios (CNR) were calculated: CNR1 - the contrast between edema and healthy myocardium and CNR2 - the contrast between edema and intraventricular blood pool. The area of edema was measured for both TIRM and DWI sequences and compared with the infarct size in LGE images. Results Edema occurred more frequently in the DWI sequence. A major difference was observed in the inferior wall, where an edema-high signal was observed in 46% in T2-TIRM, whereas in the DWI sequence in 85%. An analysis of the image quality parameters showed that the use of DWI sequence allows complete blood signal suppression in the left ventricular cavity and reduces the occurrence of motion artifacts. However, it is connected with a higher incidence of magnetic susceptibility artifacts and image distortion. An analysis of the CNRs showed that CNR1 in T2-TIRM sequence depends on the infarct location and has the lowest value for the inferior wall. The area of edema measured on DWI images was significantly larger than in T2-TIRM. Conclusions DWI is a new technique for edema detection in patients with acute myocardial infarction which may be recommended for the diagnosis of acute injuries, especially in patients with slow-flow artifacts in TIRM images. PMID:24098944

2013-01-01

382

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

SciTech Connect

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

Rancati, Tiziana [Prostate Program, Istituto Nazionale dei Tumori, Milano (Italy); Fiorino, Claudio, E-mail: fiorino.claudio@hsr.i [Medical Physics, San Raffaele Scientific Institute, Milano (Italy); Sanguineti, Giuseppe [Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States)

2009-11-01

383

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

PubMed

Tan Yue, Wen Xiaosa, Qi Ruirui, Shi Wencai, Xin Hailiang, and Li Min. The effects of Portulaca oleracea on hypoxia-induced pulmonary edema in mice. High Alt Med Biol 16:43-51, 2015-Portulaca oleracea L. (PO) is known as "a vegetable for long life" due to its antioxidant, anti-inflammatory, and other pharmacological activities. However, the protective activity of the ethanol extract of PO (EEPO) against hypoxia-induced pulmonary edema has not been fully investigated. In this study, we exposed mice to a simulated altitude of 7000 meters for 0, 3, 6, 9, and 12?h to observe changes in the water content and transvascular leakage of the mouse lung. It was found that transvascular leakage increased to the maximum in the mouse lung after 6?h exposure to hypobaric hypoxia. Prophylactic administration of EEPO before hypoxic exposure markedly reduced the transvascular leakage and oxidative stress, and inhibited the upregulation of NF-kB in the mouse lung, as compared with the control group. In addition, EEPO significantly reduced the levels of proinflammatory cytokines and cell adhesion molecules in the lungs of mice, as compared with the hypoxia group. Our results show that EEPO can reduce initial transvascular leakage and pulmonary edema under hypobaric hypoxia conditions. PMID:25761168

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

2015-03-01

384

MicroRNA-339-5p down-regulates protein expression of ?-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects.  

PubMed

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

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

2014-02-21

385

Higenamine reduces HMGB1 during hypoxia-induced brain injury by induction of heme oxygenase-1 through PI3K/Akt/Nrf-2 signal pathways.  

PubMed

Growing lines of evidence suggests that high mobility group box-1 (HMGB1) plays an important role for promoting inflammation and apoptosis in brain ischemia. Previously, we demonstrated that inducers of heme oxygenase-1 (HO-1) significantly reduce HMGB1 release in inflammatory conditions in vitro and in vivo. Thus, we tested our hypothesis that higenamine protects brain injury by inhibition of middle cerebral artery occlusion (MCAO)-mediated HMGB1 release in vivo, and glucose/glucose oxidase (GOX)-induced apoptosis in C6 cells in vitro due to HO-1 induction. Higenamine increased HO-1 expression in C6 cells in both hypoxia and normoxia, in which the former was much more significant than the latter. Higenamine increased Nrf-2 luciferase activity, translocated Nrf-2 to nucleus, and increased phosphorylation of Akt in C6 cells. Consistent with this, LY 294002, a PI3K inhibitor, inhibited HO-1 induction by higenamine and apoptosis induced by glucose/GOX in C6 cells was prevented by higenamine, which effect was reversed by LY 294002. Importantly, administration of higenamine (i.p) significantly reduced brain infarct size, mortality rate, MPO activity and tissue expression of HMGB1 in MCAO rats. In addition, recombinant high mobility group box 1 induced apoptosis in C6 cells by increasing ratio of Bax/bcl-2 and cleaved caspase c, which was inhibited by higenamine, and all of these effects were reversed by co-treatment with ZnPPIX. Therefore, we conclude that higenamine, at least in part, protects brain cells against hypoxic damages by up-regulation of HO-1. Thus, higenamine may be beneficial for the use of ischemic injuries such as stroke. PMID:22183510

Ha, Yu Mi; Kim, Min Young; Park, Min Kyu; Lee, Young Soo; Kim, Young Min; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl

2012-05-01

386

Synthetic smoke with acrolein but not HCl produces pulmonary edema  

SciTech Connect

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in