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Sample records for lipiodol induced cerebral

  1. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis

    PubMed Central

    Kirschen, Matthew P.; Dori, Yoav; Itkin, Maxim; Licht, Daniel J.; Ichord, Rebecca; Vossough, Arastoo

    2016-01-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. PMID:27297208

  2. Cerebral Lipiodol Embolism: A Complication of Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

    SciTech Connect

    Matsumoto, Koichi Nojiri, Junichi; Takase, Yukinori; Egashira, Yoshikazu; Azama, Shinichi; Kato, Akira; Kitahara, Kenji; Miyazaki, Koji; Kudo, Sho

    2007-06-15

    We report a case of cerebral lipiodol embolism following transcatheter chemoembolization (TACE) for hepatocellular carcinoma. A 70-year-old woman with a large unresectable hepatocellular carcinoma underwent TACE. Her level of consciousness deteriorated after the procedure, and magnetic resonance imaging and non-contrast computed tomography revealed a cerebral lipiodol embolism. Despite intensive care, the patient died 2 weeks later. The complication might have been due to systemic-pulmonary shunts caused by previous surgeries and/or direct invasion of the recurrent tumor.

  3. Optimization of hepatocarcinoma uptake with radiolabeled lipiodol: development of new lipiodol formulations with increased viscosity.

    PubMed

    Becker, Stéphanie; Lepareur, Nicolas; Cadeillan, Virginie; Ardisson, Valérie; Bayat, Sahar; Noiret, Nicolas; Garin, Etienne

    2012-03-01

    The aim of this study was to develop new Lipiodol formulations with increased viscosities to augment Lipiodol embolic effect and optimize efficiency of radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations consist of Lipiodol mixtures with different stearic acid concentrations (0.8%, 1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity, rheologic profiles) and labeled with 99mTc. Their viscosities at 20°C are 54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second, their biodistribution profiles were studied in vivo, at 24 and 72 hours, in hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol). Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum obtained with 1.3% stearic acid, and a tumor uptake superior to control group (+67%) (p<0.05). At 72 hours, optimal tumor uptake is reached with the 0.8% formulation, with 89% increase compared with control group (p<0.05). Moreover, we show a tendency to the decrease of pulmonary uptake for the new formulations at 24 hours and 72 hours. These results suggest a correlation between viscosity and Lipiodol tumor uptake. The new 0.8% stearic acid/Lipiodol formulation appears to be the optimized formulation for Lipiodol treatments of hepatocarcinoma, since it leads to a significant increase of tumor uptake at 72 hours and possibly to a decrease of undesirable pulmonary effects.

  4. Caffeine induced changes in cerebral circulation

    SciTech Connect

    Mathew, R.J.; Wilson, W.H.

    1985-09-01

    While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the TTXenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differences between the three sets of cerebral blood flow values.

  5. Lipiodol enhanced CT scanning of malignant hepatic tumors.

    PubMed

    Eurvilaichit, C

    2000-04-01

    From August 1984 to March 1991, 41 patients with malignant liver tumors, 30 males and 11 females, aged 30-75 years were treated at Ramathibodi Hospital with injection of mitomycin-C lipiodol emulsion into the tumor via the feeding artery followed by embolization of the feeding artery with gelfoam particles. The patients comprised 30 cases of hepatocellular carcinoma, 4 cases of cholangiocarcinoma and 7 cases of metastatic tumors of which one was from CA stomach, three were from CA breast, and three from CA colon. The vascularity of the tumor was assessed in angiogram obtained prior to treatment and retention pattern of lipiodol in the tumor was evaluated in lipiodol-enhanced CT scan images taken 2-4 weeks following therapy. The results showed that lipiodol CT scan images exhibited four patterns of lipiodol retention in the tumor appearing as opacity as follows (1) homogenous (2) heterogeneous (3) ring-like and (4) none. Lipiodol retention pattern appeared to be somewhat related to vascularity of the tumor. Most of the hypervascular tumors such as hepatocellular carcinoma had homogeneous lipiodol accumulation pattern if the tumor size was less than 5 cm. Metastatic tumors and cholangiocarcinoma showed heterogeneous or ring-like pattern of lipiodol accumulation because they were relatively hypovascular. Hypervascular hepatocellular carcinoma may exhibit heterogeneous or ring-like pattern if they are larger than 5 cms, and have multiple feeding arteries, necrosis or AV shunting. Hepatocellular carcinoma with AV shunting may not show any lipiodol accumulation at all.

  6. Venous malformations: Sclerotherapy with a mixture of ethanol and lipiodol

    SciTech Connect

    Suh, Jin-Suck; Shin, Kyoo-Ho; Na, Jae-Bum; Won, Jong-Yun; Hahn, Soo-Bong

    1997-07-15

    Purpose. To evaluate the usefulness of a mixture of absolute ethanol and lipiodol in the management of venous malformations. Methods. Percutaneous sclerotherapy was performed with a mixture of absolute ethanol and lipiodol (9:1) in 17 patients with venous malformations, once in 12 patients, twice in 5. The therapeutic efficacy was evaluated by pain reduction. Conventional radiographs (n=15) and posttreatment magnetic resonance imaging (n=5) were obtained for the follow-up evaluation. Results. Sclerotherapy was successful in all but two patients. The therapeutic effect was excellent in two patients, good in seven, fair in five, and poor in one. Radiopacity of lipiodol was beneficial for monitoring the procedure rather than for follow-up evaluations. Areas with low signal-intensity strands were increased on T2-weighted images obtained after the sclerotherapy. Conclusion. Sclerotherapy with a mixture of ethanol and lipiodol is effective in treating venous malformations.

  7. Adjuvant Iodine131 Lipiodol after Resection of Hepatocellular Carcinoma

    PubMed Central

    Furtado, Ruelan V.; Ha, Leo; Clarke, Stephen; Sandroussi, Charbel

    2015-01-01

    Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I131 lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I131 lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I131 lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I131 lipiodol group (p = 0.75). The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I131 lipiodol group (p = 0.16). Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I131 lipiodol. PMID:26713092

  8. Diet-induced ketosis does not cause cerebral acidosis.

    PubMed

    Al-Mudallal, A S; LaManna, J C; Lust, W D; Harik, S I

    1996-03-01

    Ketosis is beneficial for seizure control, possibly through induction of cerebral acidosis. However, cerebral intracellular pH has not previously been measured in ketotic humans and the animal data are sparse. We describe a high-fat diet, avidly consumed by rats, that induced consistent and moderate ketosis. Adult male rats were fed either the high-fat ketogenic diet, a high-carbohydrate diet with the same protein content as the ketogenic diet, or regular laboratory chow. Five to 6 weeks later, the rats were anesthetized, paralyzed, and injected with neutral red; their brains were frozen in situ. Intracellular pH of the cerebral cortex and cerebral glucose, lactate, ATP, phosphocreatine, and gama-aminobutyric acid (GABA) levels were measured. Rats fed the ketogenic diet had > 10-fold increase in their plasma ketones, but we noted no significant differences in cerebral pH or in cerebral metabolites and GABA levels among the three groups. Therefore, the antiepileptic effect of the ketogenic diet probably is not mediated by cerebral acidosis or changes in total cerebral GABA levels.

  9. Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.

    PubMed

    Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro; Dacey, Ralph G

    2016-06-01

    We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH.

  10. [Effect of lipiodol emulsion and local hyperthermia on hepatic tissue blood flow in rabbits with VX-2 liver tumor].

    PubMed

    Suzuki, K; Tada, I; Okada, K; Kim, Y I; Kobayashi, M

    1988-08-01

    The effect of intra-arterial infusion of lipiodol-emulsion and local hyperthermia on tissue blood flow was examined in experimental hepatic tumor and normal liver of rabbits. VX-2 tumor was implanted in liver of rabbit. The tissue blood flow was estimated by hydrogen gas clearance method when the tumor grew to about 2 cm. Tissue blood flow in tumor (64.5 ml/min/100 g) was significantly less than in normal liver (90.8 ml/min/100 g) (p less than 0.005). The intra-arterial infusion of lipiodol-emulsion did not alter the flow in either tissue. However, the addition of hyperthermia induced a substantial rise of tissue blood flow in normal liver (35% increase, from 93.8 to 127 ml/min/100 g) when compared with in VX-2 tumor (8.9% increase, from 65.1 to 71.8 ml/min/100 g). These were accompanied by a selective heating of liver tumor; the tumor temperature rose to 43 degrees C, although that of normal liver remained at 38 degrees C. Our results suggested that a specific temperature rise of liver tumor after infusion of lipiodol-emulsion and local heating might be related to a different response of microcirculation in tumor and normal liver to the hyperthermia.

  11. Arterial Embolization of Unresectable Hepatocellular Carcinoma with Use of Microspheres, Lipiodol, and Cyanoacrylate

    SciTech Connect

    Rand, Thomas Loewe, Christian; Schoder, Maria; Schmook, Maria Theresa; Peck-Radosavljevic, Markus; Kettenbach, Joachim; Wolf, Florian; Schneider, Barbara; Lammer, Johannes

    2005-04-15

    We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700{mu}) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed. Cumulative survival rates were calculated. No patient died during embolization or within the first 24 hours. Severe procedure-related complications were observed in 2 patients. At the time of analysis, 38 of 46 patients were alive. The 180-, 360-, 520-, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days. TAE with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. Bland embolization with the use of microspheres can be used in patients for whom chemoembolization is not desired.

  12. Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration.

    PubMed

    Tai, K-K; Nguyen, N; Pham, L; Truong, D D

    2008-07-01

    Ketogenic diet (KD) is an effective treatment for intractable epilepsies. We recently found that KD can prevent seizure and myoclonic jerk in a rat model of post-hypoxic myoclonus. In the present study, we tested the hypothesis that KD can prevent the cerebral ischemic neurodegeneration in this animal model. Rats fed a standard diet or KD for 25 days were being subjected to mechanically induced cardiac arrest brain ischemia for 8 min 30 s. Nine days after cardiac arrest, frozen rat brains were sectioned for evaluation of ischemia-induced neurodegeneration using fluoro-jade (FJ) staining. The FJ positive degenerating neurons were counted manually. Cardiac arrest-induced cerebral ischemia in rats fed the standard diet exhibited extensive neurodegeneration in the CA1 region of the hippocampus, the number of FJ positive neurons was 822+/-80 (n=4). They also showed signs of neurodegeneration in the Purkinje cells of the cerebellum and in the thalamic reticular nucleus, the number of FJ positive neurons in the cerebellum was 55+/-27 (n=4), the number of FJ positive neurons in the thalamic reticular nucleus was 22+/-5 (n=4). In contrast, rats fed KD showed no evidence of neurodegeneration, the number of FJ positive neurons in these areas were zero. The results demonstrate that KD can prevent cardiac arrest-induced cerebral ischemic neurodegeneration in selected brain regions.

  13. Holmium-lipiodol-alginate microspheres for fluoroscopy-guided embolotherapy and multimodality imaging.

    PubMed

    Oerlemans, Chris; Seevinck, Peter R; Smits, Maarten L; Hennink, Wim E; Bakker, Chris J G; van den Bosch, Maurice A A J; Nijsen, J Frank W

    2015-03-30

    Embolotherapy is a minimally invasive transcatheter technique aiming at reduction or complete obstruction of the blood flow by infusion of micro-sized particles in order to induce tumor regression. A major drawback of the current commercially available and clinically used microspheres is that they cannot be detected in vivo with medical imaging techniques, impeding intra- and post-procedural feedback. It can be expected that real-time monitoring of microsphere infusion and post-procedural imaging will result in better predictability and higher efficacy of the treatment. In this study, a novel microsphere formulation has been developed that can be visualized with fluoroscopy, X-ray computed tomography (CT) and magnetic resonance imaging (MRI). The microspheres were prepared with the JetCutter technique and consist of alginate (matrix-forming polymer), holmium (cross-linking and MRI contrast agent), lipiodol (radiopaque contrast agent) and Pluronic F-68 (surfactant). The mean size (±SEM) of the hydrated holmium-lipiodol-alginate microspheres (Ho-lip-ams) was 570±12 μm with a holmium content of 0.38±0.01% (w/w). Stability studies showed that the microspheres remained intact during incubation for two weeks in fetal calf serum (FCS) at 37 °C. The inclusion of lipiodol in the microspheres rendered excellent visualization capabilities for fluoroscopy and CT, whereas the holmium ions, which keep the alginate network together, also allow MR imaging. In this study it was shown that single sphere detection was possible by fluoroscopy, CT and MRI. The Ho-lip-ams were visualized in real-time, during infusion in a porcine kidney using fluoroscopy, and post-procedural, the deposition of the microspheres was examined with fluoroscopy, (cone beam rotational) CT and MRI. The different imaging modalities showed similar deposition patterns of the microspheres within the organ. The combination of intra-procedural visualization, multimodality imaging for patient follow-up and the

  14. Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion

    SciTech Connect

    Baere, Thierry de; Arai, Yasuaki; Lencioni, Riccardo; Geschwind, Jean-Francois; Rilling, William; Salem, Riad; Matsui, Osamu; Soulen, Michael C.

    2016-03-15

    Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014.

  15. Automation of labelling of Lipiodol with high-activity generator-produced 188Re.

    PubMed

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Boucher, Eveline; Raoul, Jean-Luc; Clément, Bruno; Garin, Etienne

    2011-02-01

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52±2.3% and extraction yield was 98.56±1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68±9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ((188)Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07±0.9%).

  16. Cocaine induces apoptosis in cerebral vascular muscle cells: potential roles in strokes and brain damage.

    PubMed

    Su, Jialin; Li, Jianfeng; Li, Wenyan; Altura, Bella T; Altura, Burton M

    2003-12-15

    Cocaine abuse is known to induce different types of brain-microvascular damage and many adverse cerebrovascular effects, including cerebral vasculitis, intracranial hemorrhage, cerebral infarction and stroke. A major physiological event leading to these pathophysiological actions of cocaine could be apoptosis. Whether cocaine can cause brain-microvascular pathology and vascular toxicity by inducing apoptosis of cerebral vascular smooth muscle cells is not known. This study, using several different methods to discern apoptosis, was designed to investigate if primary cultured canine cerebral vascular smooth muscle cells can undergo apoptosis when treated with cocaine. After treatment with cocaine (10(-6)-10(-3) M) for 12-24 h, the death rates of cerebral vascular smooth muscle cells increased in a concentration-dependent manner compared with controls. Morphological analysis of cerebral vascular smooth muscle cells using confocal fluoresence microscopy showed that the percentage of apoptotic cerebral vascular smooth muscle cells increased after cocaine (10(-6)-10(-3) M) treatment in a concentration-dependent manner. TUNEL assays also showed positive results for cerebral vascular smooth muscle cells treated with cocaine. These results clearly demonstrate that cerebral vascular smooth muscle cells can undergo rapid apoptosis in response to cocaine in a concentration-dependent manner. Cocaine-induced apoptosis may thus play a major role in brain-microvascular damage, cerebral vascular toxicity and strokes.

  17. SU-D-BRB-07: Lipiodol Impact On Dose Distribution in Liver SBRT After TACE

    SciTech Connect

    Kawahara, D; Ozawa, S; Hioki, K; Suzuki, T; Lin, Y; Okumura, T; Ochi, Y; Nakashima, T; Ohno, Y; Kimura, T; Murakami, Y; Nagata, Y

    2015-06-15

    Purpose: Stereotactic body radiotherapy (SBRT) combining transarterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study aims to evaluate the impact of Lipiodol on dose distribution by comparing the dosimetric performance of the Acuros XB (AXB) algorithm, anisotropic analytical algorithm (AAA), and Monte Carlo (MC) method using a virtual heterogeneous phantom and a treatment plan for liver SBRT after TACE. Methods: The dose distributions calculated using AAA and AXB algorithm, both in Eclipse (ver. 11; Varian Medical Systems, Palo Alto, CA), and EGSnrc-MC were compared. First, the inhomogeneity correction accuracy of the AXB algorithm and AAA was evaluated by comparing the percent depth dose (PDD) obtained from the algorithms with that from the MC calculations using a virtual inhomogeneity phantom, which included water and Lipiodol. Second, the dose distribution of a liver SBRT patient treatment plan was compared between the calculation algorithms. Results In the virtual phantom, compared with the MC calculations, AAA underestimated the doses just before and in the Lipiodol region by 5.1% and 9.5%, respectively, and overestimated the doses behind the region by 6.0%. Furthermore, compared with the MC calculations, the AXB algorithm underestimated the doses just before and in the Lipiodol region by 4.5% and 10.5%, respectively, and overestimated the doses behind the region by 4.2%. In the SBRT plan, the AAA and AXB algorithm underestimated the maximum doses in the Lipiodol region by 9.0% in comparison with the MC calculations. In clinical cases, the dose enhancement in the Lipiodol region can approximately 10% increases in tumor dose without increase of dose to normal tissue. Conclusion: The MC method demonstrated a larger increase in the dose in the Lipiodol region than the AAA and AXB algorithm. Notably, dose enhancement were observed in the tumor area; this may lead to a clinical benefit.

  18. A Comparison of Three Transarterial Lipiodol-Based Formulations for Hepatocellular Carcinoma: In Vivo Biodistribution Study in Humans

    SciTech Connect

    Yu, Simon Chun Ho Leung, Thomas Wai Tong; Lau, Wan Yee; Lee, Nelson; Hui, Edwin Pun; Yeo, Winnie; Lai, Paul Bo San; Mok, Tony Shu Kam

    2008-03-15

    This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 (p = 0.014) and day 28 (p = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations.

  19. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils

    PubMed Central

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-01-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2′-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  20. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils.

    PubMed

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-04-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2'-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury.

  1. Utilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion.

    PubMed

    Regenhardt, Robert W; Ansari, Saeed; Azari, Hassan; Caldwell, Kenneth J; Mecca, Adam P

    2013-02-22

    Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain(1-3). This technique can be performed in many locations overlying the rat cerebrum, but is most easily carried out by creating a craniectomy over the readily accessible frontal or parietal bones. Most frequently, we have used this technique in combination with the endothelin-1 middle cerebral artery occlusion model of ischemic stroke to quantify the changes in middle cerebral artery vessel diameter that occur with injection of endothelin-1 into the brain parenchyma adjacent to the proximal MCA(4, 5). In order to visualize the proximal portion of the MCA during endothelin -1 induced MCAO, we use a technique to create a cranial window through the temporal bone on the lateral aspect of the rat skull (Figure 1). Cerebral arteries can be visualized either with the dura intact or with the dura incised and retracted. Most commonly, we leave the dura intact during visualization since endothelin-1 induced MCAO involves delivery of the vasoconstricting peptide into the brain parenchyma. This bypasses the need to incise the dura directly over the visualized vessels for drug delivery. This protocol will describe how to create a cranial window to visualize cerebral arteries in a step-wise fashion, as well as how to avoid many of the potential pitfalls pertaining to this method.

  2. Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure

    PubMed Central

    Taylor, Curtis R.; Hanna, Mina; Behnke, Bradley J.; Stabley, John N.; McCullough, Danielle J.; Davis, Robert T.; Ghosh, Payal; Papadopoulos, Anthony; Muller-Delp, Judy M.; Delp, Michael D.

    2013-01-01

    Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground-based animal models simulating the effects of microgravity have shown that decrements in cerebral perfusion are associated with enhanced vasoconstriction and structural remodeling of cerebral arteries. Based on these results, the purpose of this study was to test the hypothesis that 13 d of spaceflight [Space Transportation System (STS)-135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall thickness, and elicits no change in the mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCAs) were isolated from 9-wk-old female C57BL/6 mice for in vitro vascular and mechanical testing. Contrary to that hypothesized, myogenic vasoconstrictor responses were lower and vascular distensibility greater in arteries from spaceflight group (SF) mice (n=7) relative to ground-based control group (GC) mice (n=12). Basilar artery maximal diameter was greater in SF mice (SF: 236±9 μm and GC: 215±5 μm) with no difference in medial wall thickness (SF: 12.4±1.6 μm; GC: 12.2±1.2 μm). Stiffness of the PCA, as characterized via nanoindentation, was lower in SF mice (SF: 3.4±0.3 N/m; GC: 5.4±0.8 N/m). Collectively, spaceflight-induced reductions in myogenic vasoconstriction and stiffness and increases in maximal diameter of cerebral arteries signify that elevations in brain blood flow may occur during spaceflight. Such changes in cerebral vascular control of perfusion could contribute to increases in intracranial pressure and an associated impairment of visual acuity in astronauts during spaceflight.—Taylor, C. R., Hanna, M., Behnke, B. J., Stabley, J. N., McCullough, D. J., Davis III, R. T., Ghosh, P., Papadopoulos, A., Muller-Delp, J. M., Delp, M. D. Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated

  3. Lipiodol: A Potential Direct Surrogate for Cone-Beam Computed Tomography Image Guidance in Radiotherapy of Liver Tumor

    SciTech Connect

    Yue Jinbo; Sun Xindong; Cai Jing; Yin Fangfang; Yin Yong; Zhu Jian; Lu Jie; Liu Tonghai; Yu Jinming; Shi Xuetao; Song Jinlong

    2012-02-01

    Purpose: To investigate the feasibility of using lipiodol as a direct surrogate for target localization using cone-beam CT (CBCT) image guidance in radiotherapy (RT) of patients with unresectable liver tumors after transarterial chemoembolization. Methods and Materials: Forty-six patients with an unresectable solitary liver tumor were enrolled for RT using active breathing control (ABC) and CBCT image guidance after transarterial chemoembolization. Each patient had pre- and posttreatment CBCT in the first 10 fractions of treatment. Lipiodol retention was evaluated using daily CBCT scans, and volume of lipiodol retention in the liver was calculated and compared between planning CT and post-RT CT. Influence of lipiodol on dosimetry was evaluated by measuring doses using an ion chamber with and without the presence of lipiodol. Margin analysis was performed on the basis of both inter- and intrafractional target localization errors. Results: Twenty-eight patients successfully completed the study. The shape and size of lipiodol retention did not vary substantially during the course of treatment. The mean Dice similarity coefficient for the lipiodol volume in pretreatment CT and that in posttreatment CT was 0.836 (range, 0.817-0.885). The maximum change (ratio of the lipiodol volume in pretreatment CT to that in posttreatment CT) was 1.045. The mean dose changes with the presence of <10 mL lipiodol were -1.44% and 0.13% for 6 MV and 15 MV, respectively. With ABC and online CBCT image guidance, clinical target volume-planning target volume margins were determined to be 2.5 mm in the mediolateral direction, 2.9 mm in the anteroposterior direction, and 4.0 mm in the craniocaudal direction. Conclusions: Lipiodol could be used as a direct surrogate for CBCT image guidance to improve the localization accuracy for RT of liver tumors. Combination of ABC and CBCT image guidance with lipiodol can potentially reduce the clinical target volume-planning target volume margin.

  4. [Comparative evaluation of ultrasonography, computerized tomography, angiography and lipiodol CT in defining extent of hepatocarcinoma. A multicenter study].

    PubMed

    Dalla Palma, L; Pozzi Mucelli, R; Sponza, M; Bartolozzi, C; De Santis, M; Gandini, G; Mannella, P; Matricardi, L; Rossi, C; Simonetti, G

    1995-03-01

    The authors report the results of a multicentric trial on hepatocellular carcinoma (HCC) patients, whose lesions were confirmed with biopsy or by high (> 400 ng/ml) alpha-fetoprotein levels. The series consisted of 149 patients examined in 8 different centers and submitted to ultrasonography (US), Computed Tomography (CT) before and after contrast agent administration, angiography and Lipiodol CT. According to lesion size and number, the patients were divided with each imaging modality into three groups: a) group 1: unifocal HCC < 5 cm diameter; b) group 2: multifocal HCC with 2-3 nodules and/or tumor mass < 80 ml; c) multifocal HCC with more than 3 nodules (with total tumor mass not exceeding 40% of liver volume) or with total tumor mass > 80 ml. In 77 patients all the examinations were available for comparison. US and CT diagnosed more patients as belonging to group 1 than angiography and Lipiodol CT, while more patients were classified as groups 2 and 3 with angiography and Lipiodol CT, meaning that US and CT may understage some HCC cases (about 15%) because they show a lower number of nodules. This observation was confirmed by the direct comparison between US and Lipiodol CT (in 114 patients), CT and Lipiodol CT (in 103 patients) and angiography and Lipiodol CT (in 116 patients). US and Lipiodol CT were in disagreement in 18 cases, CT and Lipiodol CT in 16 cases and angiography and Lipiodol CT in 13 cases. In most of these cases, Lipiodol CT showed more lesions than the other techniques. The size of the undetected lesions was small, ranging few mm to 2 cm in nearly all cases. To conclude, the results of this multicentric trial show that Lipiodol CT is a fundamental tool to evaluate HCC extent. In contrast, conventional CT appeared not to add any significant piece of information and can therefore be excluded from the diagnostic protocol of HCC.

  5. Music-induced changes in functional cerebral asymmetries.

    PubMed

    Hausmann, Markus; Hodgetts, Sophie; Eerola, Tuomas

    2016-04-01

    After decades of research, it remains unclear whether emotion lateralization occurs because one hemisphere is dominant for processing the emotional content of the stimuli, or whether emotional stimuli activate lateralised networks associated with the subjective emotional experience. By using emotion-induction procedures, we investigated the effect of listening to happy and sad music on three well-established lateralization tasks. In a prestudy, Mozart's piano sonata (K. 448) and Beethoven's Moonlight Sonata were rated as the most happy and sad excerpts, respectively. Participants listened to either one emotional excerpt, or sat in silence before completing an emotional chimeric faces task (Experiment 1), visual line bisection task (Experiment 2) and a dichotic listening task (Experiment 3 and 4). Listening to happy music resulted in a reduced right hemispheric bias in facial emotion recognition (Experiment 1) and visuospatial attention (Experiment 2) and increased left hemispheric bias in language lateralization (Experiments 3 and 4). Although Experiments 1-3 revealed an increased positive emotional state after listening to happy music, mediation analyses revealed that the effect on hemispheric asymmetries was not mediated by music-induced emotional changes. The direct effect of music listening on lateralization was investigated in Experiment 4 in which tempo of the happy excerpt was manipulated by controlling for other acoustic features. However, the results of Experiment 4 made it rather unlikely that tempo is the critical cue accounting for the effects. We conclude that listening to music can affect functional cerebral asymmetries in well-established emotional and cognitive laterality tasks, independent of music-induced changes in the emotion state.

  6. Ischemic Effects of Transcatheter Arterial Embolization with N-Butyl Cyanoacrylate-Lipiodol on the Colon in a Swine Model

    SciTech Connect

    Ikoma, Akira; Kawai, Nobuyuki; Sato, Morio Sonomura, Tetsuo; Minamiguchi, Hiroki; Nakai, Motoki; Takasaka, Isao; Nakata, Kouhei; Sahara, Shinya; Sawa, Naohisa; Shirai, Shintaro; Mori, Ichiro

    2010-10-15

    This study was designed to assess the safety of transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate-lipiodol (NBCA-Lp) for the large bowel and to investigate the vital response to NBCA-Lp in a swine model. In nine swine, nine arteries nourishing the colon were embolized with NBCA-Lp (1 ml of NBCA mixed with 4 ml of lipiodol): sigmoid-rectal branch artery in six swine, right colic branch artery in two, and middle colic branch artery in one. The amount of NBCA-Lp was 0.1-0.4 ml. Sacrifice was conducted 3 days after TAE to identify histological infarction. Classification was conducted retrospectively: group A, vasa recta without NBCA-Lp embolization despite TAE; group B, three or fewer vasa recta with NBCA-Lp embolization; and group C, five or more vasa recta with NBCA-Lp embolization. In one swine in group A, no necrotic focus was observed. In group B, three of four swine experienced no ischemic damage. The remaining one swine experienced necrosis of mucosal and submucosal layers in one-fourth of the circumference. In group C, all four swine with marginal artery and five vasa recta or more embolized experienced total necrosis of mucosa, submucosa, and smooth muscle layers of the whole colonic circumference. Significant difference on the extent of ischemic damage was observed between groups B and C (P < 0.05). Microscopically, NBCA-Lp induced acute vasculitis. Embolization of three or fewer vasa recta with NBCA-Lp induced no ischemic damage or limited necrosis, whereas embolization of five or more vasa recta with NBCA-Lp induced extensive necrosis.

  7. Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury.

    PubMed

    Li, Chun; Sun, Hong; Arrick, Denise M; Mayhan, William G

    2016-02-01

    Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg·kg(-1)·day(-1)) for 4 wk via an implanted subcutaneous osmotic minipump and subjected to a 2-h middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 h of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase but significantly decreased MnSOD and uncoupling protein-2 (UCP-2) in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a preexisting oxidative stress via decreasing of MnSOD and UCP-2.

  8. Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia

    PubMed Central

    Chen, Han; Wei, Aixuan; He, Jinting; Yu, Ming; Mang, Jing; Xu, Zhongxin

    2013-01-01

    Hypoxia-inducible factor-1 and its specific target gene heme oxygenase-1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hypoxia-inducible factor-1/heme oxygenase-1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol (30 mg/kg) for 9 weeks. Morris water maze results showed that cognitive impairment gradually worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative PCR and western blot analysis showed that hypoxia-inducible factor-1α and heme oxygenase-1 expression levels increased after chronic cerebral ischemia, with hypoxia-inducible factor-1α expression peaking at 3 weeks and heme oxygenase-1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxia-inducible factor-1α may upregulate heme oxygenase-1 expression following chronic cerebral ischemia and that the hypoxia-inducible factor-1/heme oxygenase-1 signaling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, decreased hypoxia-inducible factor-1α and heme oxygenase-1 expression levels, and reduced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an anti-apoptotic mechanism. PMID:25206477

  9. 188Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside

    PubMed Central

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (Eβmax = 2.1 MeV) for the treatment of HCC. The major “milestones” of this development, from the first syntheses to the recent first injection in man, are described. PMID:22518301

  10. (188)Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside.

    PubMed

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (E(βmax) = 2.1 MeV) for the treatment of HCC. The major "milestones" of this development, from the first syntheses to the recent first injection in man, are described.

  11. PUMA is invovled in ischemia/reperfusion-induced apoptosis of mouse cerebral astrocytes.

    PubMed

    Chen, H; Tian, M; Jin, L; Jia, H; Jin, Y

    2015-01-22

    PUMA (p53-upregulated modulator of apoptosis), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and p53-independent forms of apoptosis. PUMA has been invovled in the onset and progress of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease. Although many studies have shown that ischemia and reperfusion (I/R) can induce the apoptosis of astrocytes, the role of PUMA in I/R-mediated apoptosis of cerebral astrocyte apoptosis remains unclear. To mimic in vivo I/R conditions, primary mouse cerebral astrocytes were incubated in a combinational cultural condition of oxygen, glucose, and serum deprivation (OSGD) for 1 h followed by reperfusion (OSGD/R). Cell death determination assays and cell viability assays indicated that OSGD and OSGD/R induce the apoptosis of primary cerebral astrocytes. The expression of PUMA was significantly elevated in primary cerebral astrocytes during OSGD/R. Moreover, targeted down-regulation of PUMA by siRNA transfection significantly decreased the OSGD/R-induced apoptosis of primary cerebral astrocytes. We also found that OSGD and OSGD/R triggered the release of cytochrome c in astrocytes, indicating the dependence on a mitochondrial apoptotic pathway. Reactive oxygen species (ROS) was extremely generated during OSGD and OSGD/R, and the elimination of ROS by treated with N-acetyl-L-cysteine (NAC) remarkably inhibited the expression of PUMA and the apoptosis of primary cerebral astrocytes. The activation of Caspase 3 and Caspase 9 was extremely elevated in primary cerebral astrocytes during OSGD. In addition, we found that knockdown of PUMA led to the depressed expression of Bax, cleaved caspase-9 and caspase-3 during OSGD/R. These results indicate that PUMA is invovled in the apoptosis of cerebral astrocytes upon I/R injury.

  12. [Perspectives in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm].

    PubMed

    Fandino, J; Fathi, A R; Graupner, T; Jacob, S; Landolt, H

    2007-02-01

    Cerebral vasospasm is still the most important cause of death and disability after rupture of intracranial aneurysms. The therapeutic strategies in the treatment of subarachnoid hemorrhage induced vasospasm vasospasm include four groups: 1) prevention of vasospasm; 2) reversion of vasospasm; 3) improvement of cerebral perfusion; and 4) neuroprotection and rescue therapies. Recent experimental studies allowed the design of phase II clinical studies which demonstrated positive results with medications and compounds such as statins (simvastatin and pravastatin) and endothelin-1 receptor antagonists (clasozentan). Moreover, experimental and clinical evidences showed the advantages of early cerebrospinal fluid drainage, intrathecal administration of NO-donors, effects of Ca2+ protein kinase inhibitor (Fasudil) and catecholamines on the cerebral vessels. This review article summarizes the stage of investigation of these medications and therapeutic strategies which will be relevant in the treatment of cerebral vasospasm.

  13. Multiple cerebral infarctions in a young patient with heroin-induced hypereosinophilic syndrome.

    PubMed

    Bolz, Jan; Meves, Saskia H; Kara, Kaffer; Reinacher-Schick, Anke; Gold, Ralf; Krogias, Christos

    2015-09-15

    Hypereosinophilic syndrome represents a rare cause for cerebral infarctions and inflammatory neurological disorders. Various possible pathogenic mechanisms for cerebral infarctions have already been discussed. Complex mechanisms including a local hypercoagulability by eosinophilic granules as well as a direct damage to endothelial cells, leading to alterations of the microcirculation seem to be involved. The changing pattern of heroin use to inhalation/sniffing leading to an increasing abuse may cause a rise in the prevalence of Heroin induced eosinophilia, as it has been reported in a case of eosinophilic pneumonia associated with heroin inhalation. To our knowledge, the present case report displays the first description of stroke in the setting of heroin induced hypereosinophilia. Thus, besides usual vasoconstriction, HES should be considered in drug-induced cerebral infarctions.

  14. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans.

    PubMed

    Seifert, Thomas; Fisher, James P; Young, Colin N; Hartwich, Doreen; Ogoh, Shigehiko; Raven, Peter B; Fadel, Paul J; Secher, Niels H

    2010-10-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O(2), glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V(mean); transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1) (P < 0.01) and cardiac output by approximately 40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V(mean) (approximately 16%; P < 0.01) and CBF (approximately 12%; P < 0.01) during static handgrip, as well as the increase in MCA V(mean) during cycling (approximately 15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen.

  15. Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex

    PubMed Central

    Majumdar, Anuradha S.; Nirwane, Abhijit; Kamble, Rahul

    2014-01-01

    Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3. PMID:25253934

  16. Cyclophosphamide-induced agenesis of cerebral aqueduct resulting in hydrocephalus in mice.

    PubMed

    Prakash; Singh, Gajendra; Singh, Sukh Mahendra

    2007-07-01

    The present work was undertaken to reveal the mechanism of cerebral aqueduct agenesis found to result in hydrocephalus following intrauterine exposure to model teratogen, cyclophosphamide, in murine fetuses. A single dose of 10-mg/kg body weight cyclophosphamide was injected intaperitoneally to pregnant mice on day 10, 11 or 12 of gestation. Fetuses were collected through abdominal incision on day 18 and studied for various malformations of brain and cranium including hydrocephalus. Incomplete development and failure of canalization of the cerebral aqueduct were detected when serial sections of brain in coronal and transverse planes were studied under the microscope. Biotechnological investigations such as % DNA fragmentation, % viable cell count and cell proliferation assay were carried out on brain cells for further studies. Agenesis and non-canalization of the cerebral aqueduct resulted in increased pressure of CSF, which led to rupture of the aqueduct complicated by leakage and accumulation of CSF in brain substance forming a cavity containing CSF parallel and lateral to the unopened part of the cerebral aqueduct. Incomplete development along with non-canalization of the cerebral aqueduct resulted in blockage of CSF flow through the ventricles that manifest as internal hydrocephalus. External hydrocephalus on the other hand was detected where the CSF accumulated in the cavity formed inside the brain substance and established communication with the CSF in the subarachnoid space. Cyclophosphamide induced inhibition of mitosis and cell differentiation of ependymal cells reflecting a decreased % viable cell count and cell proliferation assay along with augmentation of apoptosis of brain cells quantified as increased % DNA fragmentation count, which were identified as the contributing factors underlying the agenesis and incomplete development of the cerebral aqueduct. The study also suggests that cell survival, proliferation, migration or differentiation of

  17. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction

    PubMed Central

    Chang, Jennifer; Fedinec, Alexander L.; Kuntamallappanavar, Guruprasad; Leffler, Charles W.; Bukiya, Anna N.

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from “energy drinks”) continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40–70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS−/−) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  18. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction.

    PubMed

    Chang, Jennifer; Fedinec, Alexander L; Kuntamallappanavar, Guruprasad; Leffler, Charles W; Bukiya, Anna N; Dopico, Alex M

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  19. Hypertension-Induced Vascular Remodeling Contributes to Reduced Cerebral Perfusion and the Development of Spontaneous Stroke in Aged SHRSP Rats

    DTIC Science & Technology

    2010-01-01

    induced vascular remodeling contributes to reduced cerebral perfusion and the development of spontaneous stroke in aged SHRSP rats Erica C Henning1...spontaneously-hypertensive, stroke-prone (SHRSP) rats is of particular interest because the pathogenesis is believed to be similar to that in the...cerebral infarction and the specific role of cerebral perfusion in disease development. Twelve female SHRSP rats (age: - 1 year) were Imaged within 1

  20. Influence of Lipiodol Agent on Proton Beam Range in Radiotherapy Planning Using Computed Tomography for Hepatocellular Carcinoma

    SciTech Connect

    Shin, Dongho; Kim, Tae Hyun; Park, Sung Yong Kwak, Jungwon; Moon, Sung Ho; Yoon, Myonggeun; Lee, Se Byeong; Park, Soah; Shin, Kyung Hwan; Kim, Dae Yong; Cho, Kwan Ho; Park, Joong-Won; Kim, Chang-Min

    2008-11-01

    Purpose: To evaluate the influence of lipiodol on the proton beam range, which has not yet been determined. Methods and Materials: Two computed tomography (CT) data sets were obtained with a T25-flask containing lipiodol and water that was placed above a water phantom. The plan with the lipiodol CT images was performed, and then a verification plan was applied to the water CT images. The actual proton beam ranges in the lipiodol and water were measured under same conditions, and we compared the calculated proton beam range in the treatment planning system with measured values. Results: The calculated distal range in the treatment planning system was 12 cm in water, which was 3.87 cm longer than that in lipiodol (8.13 cm). In contrast, the measured distal range was 12 {+-} 0.01 cm in water, which was 0.21 {+-} 0.01 cm longer than that of lipiodol (11.78 {+-} 0.01 cm). A 3.65 {+-} 0.01-cm range shift was found in the calculated range compared with the measured range. For 10 hepatocellular carcinoma patients, the distal range in the verification plan with the corrected CT images in which the Hounsfield unit (HU) value of lipiodolized lesion was replaced with the average HU value of the surrounding tissue was 0.61 {+-} 0.26 cm (range, 0.26-0.99) longer than that in the plan with uncorrected CT images. Conclusions: It could be relevant for the purposes of range calculation of proton beams in the treatment planning system that the HU value of a lipiodolized lesion is replaced by the average HU value of the surrounding normal tiss0008.

  1. Cerebral blood flow changes during sodium-lactate-induced panic attacks

    SciTech Connect

    Stewart, R.S.; Devous, M.D. Sr.; Rush, A.J.; Lane, L.; Bonte, F.J.

    1988-04-01

    Dynamic single-photon emission computed axial tomography (CAT) with inhaled xenon-133 was used to measure regional cerebral blood flow in 10 drug-free patients with DSM-III-diagnosed panic disorder and in five normal control subjects. All subjects underwent regional cerebral blood flow studies while at rest or during normal saline infusion and during sodium lactate infusion. Six of the 10 patients and none of the control subjects experienced lactate-induced panic attacks. Lactate infusion markedly raised hemispheric blood flow levels in both control subjects and patients who did not panic. Patients who did panic experienced either a minimal increase or a decrease in hemispheric blood flow.

  2. Traumatic Brain Injury by a Closed Head Injury Device Induces Cerebral Blood Flow Changes and Microhemorrhages

    PubMed Central

    Kallakuri, Srinivasu; Bandaru, Sharath; Zakaria, Nisrine; Shen, Yimin; Kou, Zhifeng; Zhang, Liying; Haacke, Ewart Mark; Cavanaugh, John M

    2015-01-01

    Objectives: Traumatic brain injury is a poly-pathology characterized by changes in the cerebral blood flow, inflammation, diffuse axonal, cellular, and vascular injuries. However, studies related to understanding the temporal changes in the cerebral blood flow following traumatic brain injury extending to sub-acute periods are limited. In addition, knowledge related to microhemorrhages, such as their detection, localization, and temporal progression, is important in the evaluation of traumatic brain injury. Materials and Methods: Cerebral blood flow changes and microhemorrhages in male Sprague Dawley rats at 4 h, 24 h, 3 days, and 7 days were assessed following a closed head injury induced by the Marmarou impact acceleration device (2 m height, 450 g brass weight). Cerebral blood flow was measured by arterial spin labeling. Microhemorrhages were assessed by susceptibility-weighted imaging and Prussian blue histology. Results: Traumatic brain injury rats showed reduced regional and global cerebral blood flow at 4 h and 7 days post-injury. Injured rats showed hemorrhagic lesions in the cortex, corpus callosum, hippocampus, and brainstem in susceptibility-weighted imaging. Injured rats also showed Prussian blue reaction products in both the white and gray matter regions up to 7 days after the injury. These lesions were observed in various areas of the cortex, corpus callosum, hippocampus, thalamus, and midbrain. Conclusions: These results suggest that changes in cerebral blood flow and hemorrhagic lesions can persist for sub-acute periods after the initial traumatic insult in an animal model. In addition, microhemorrhages otherwise not seen by susceptibility-weighted imaging are present in diverse regions of the brain. The combination of altered cerebral blood flow and microhemorrhages can potentially be a source of secondary injury changes following traumatic brain injury and may need to be taken into consideration in the long-term care of these cases. PMID:26605126

  3. Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage.

    PubMed

    Hou, Sheng Tao; Nilchi, Ladan; Li, Xuesheng; Gangaraju, Sandhya; Jiang, Susan X; Aylsworth, Amy; Monette, Robert; Slinn, Jacqueline

    2015-01-20

    Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia.

  4. Long Non-coding RNA H19 Induces Cerebral Ischemia Reperfusion Injury via Activation of Autophagy

    PubMed Central

    Wang, Jue; Cao, Bin; Han, Dong; Sun, Miao; Feng, Juan

    2017-01-01

    Long non-coding RNA H19 (lncRNA H19) was found to be upregulated by hypoxia, its expression and function have never been tested in cerebral ischemia and reperfusion (I/R) injury. This study intended to investigate the role of lncRNA H19 and H19 gene variation in cerebral I/R injury with focusing on its relationship with autophagy activation. Cerebral I/R was induced in rats by middle cerebral artery occlusion followed by reperfusion. SH-SY5Y cells were subjected to oxygen and glucose deprivation and reperfusion (OGD/R) to simulate I/R injury. Real-time PCR, flow cytometry, immunofluorescence and Western blot were used to evaluate the level of lncRNA H19, apoptosis, autophagy and some related proteins. The modified multiple ligase reaction was used to analyze the gene polymorphism of six SNPs in H19, rs217727, rs2067051, rs2251375, rs492994, rs2839698 and rs10732516 in ischemic stroke patients. We found that the expression of lncRNA H19 was upregulated by cerebral I/R in rats, as well as by OGD/R in vitro in the cells. Inhibition of lncRNA H19 and autophagy protected cells from OGD/R-induced death, respectively. Autophagy activation induced by OGD/R was prevented by H19 siRNA. Autophagy inducer, rapamycin, abolished lncRNA H19 effect. Furthermore, we found that lncRNA H19 inhibited autophagy through DUSP5-ERK1/2 axis. The result from blood samples of ischemic patients revealed that the variation of H19 gene increased the risk of ischemic stroke. Taken together, the results of present study suggest that LncRNA H19 could be a new therapeutic target of ischemic stroke. PMID:28203482

  5. Long Non-coding RNA H19 Induces Cerebral Ischemia Reperfusion Injury via Activation of Autophagy.

    PubMed

    Wang, Jue; Cao, Bin; Han, Dong; Sun, Miao; Feng, Juan

    2017-02-01

    Long non-coding RNA H19 (lncRNA H19) was found to be upregulated by hypoxia, its expression and function have never been tested in cerebral ischemia and reperfusion (I/R) injury. This study intended to investigate the role of lncRNA H19 and H19 gene variation in cerebral I/R injury with focusing on its relationship with autophagy activation. Cerebral I/R was induced in rats by middle cerebral artery occlusion followed by reperfusion. SH-SY5Y cells were subjected to oxygen and glucose deprivation and reperfusion (OGD/R) to simulate I/R injury. Real-time PCR, flow cytometry, immunofluorescence and Western blot were used to evaluate the level of lncRNA H19, apoptosis, autophagy and some related proteins. The modified multiple ligase reaction was used to analyze the gene polymorphism of six SNPs in H19, rs217727, rs2067051, rs2251375, rs492994, rs2839698 and rs10732516 in ischemic stroke patients. We found that the expression of lncRNA H19 was upregulated by cerebral I/R in rats, as well as by OGD/R in vitro in the cells. Inhibition of lncRNA H19 and autophagy protected cells from OGD/R-induced death, respectively. Autophagy activation induced by OGD/R was prevented by H19 siRNA. Autophagy inducer, rapamycin, abolished lncRNA H19 effect. Furthermore, we found that lncRNA H19 inhibited autophagy through DUSP5-ERK1/2 axis. The result from blood samples of ischemic patients revealed that the variation of H19 gene increased the risk of ischemic stroke. Taken together, the results of present study suggest that LncRNA H19 could be a new therapeutic target of ischemic stroke.

  6. Electroacupuncture induces acute changes in cerebral cortical miRNA profile, improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke

    PubMed Central

    Zheng, Hai-zhen; Jiang, Wei; Zhao, Xiao-feng; Du, Jing; Liu, Pan-gong; Chang, Li-dan; Li, Wen-bo; Hu, Han-tong; Shi, Xue-min

    2016-01-01

    Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters miRNA expression in the cortex. In this study, we examined changes in the cerebral cortical miRNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong (GV26) and Neiguan (PC6), with a frequency of 2 Hz, continuous wave, current intensity of 3.0 mA, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. miRNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-miR-206-3p, rno-miR-3473, rno-miR-6216 and rno-miR-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated miRNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke. PMID:28197190

  7. Cerebral oxygenation and haemodynamic effects induced by nimodipine in healthy subjects

    PubMed Central

    Canova, Daniela; Roatta, Silvestro; Micieli, Giuseppe; Bosone, Daniele

    2012-01-01

    Summary The cerebrovascular effects of nimodipine are still poorly understood even in the healthy condition; in particular, its effects on tissue oxygenation have never been investigated. The aim of the present study was to investigate changes in cerebral oxygenation and blood volume upon oral administration of nimodipine (90 mg) in the healthy condition. In eight subjects, changes in cerebral tissue oxygenation and blood volume were determined simultaneously with changes in blood velocity of the middle cerebral artery (VMCA) by using, respectively, near infrared spectroscopy (NIRS) and transcranial Doppler ultrasonography (TCD). The subjects also underwent non-invasive assessment of arterial blood pressure (ABP) and end-tidal CO2. TCD and NIRS CO2 reactivity indices were also extracted. Nimodipine significantly reduced ABP (11±13%) and increased heart rate, as well as NIRS oxygenation (6.0±4.8%) and blood volume indices (9.4±10.1%), while VMCA was not significantly decreased (2.0±3.5%). Nimodipine slightly but significantly reduced the VMCA response to changes in pCO2 whereas the CO2 reactivity of NIRS parameters was improved. The observed changes in cerebral tissue oxygenation and blood volume indicate nimodipine-induced cerebrovascular dilation and increased perfusion, while the effect on VMCA possibly results from dilation of the insonated artery. The present results cast doubt on the putative nimodipine-induced impairment of CO2 reactivity. PMID:23402678

  8. Cerebral oxygenation and haemodynamic effects induced by nimodipine in healthy subjects.

    PubMed

    Canova, Daniela; Roatta, Silvestro; Micieli, Giuseppe; Bosone, Daniele

    2012-01-01

    The cerebrovascular effects of nimodipine are still poorly understood even in the healthy condition; in particular, its effects on tissue oxygenation have never been investigated. The aim of the present study was to investigate changes in cerebral oxygenation and blood volume upon oral administration of nimodipine (90 mg) in the healthy condition. In eight subjects, changes in cerebral tissue oxygenation and blood volume were determined simultaneously with changes in blood velocity of the middle cerebral artery (VMCA) by using, respectively, near infrared spectroscopy (NIRS) and transcranial Doppler ultrasonography (TCD). The subjects also underwent noninvasive assessment of arterial blood pressure (ABP) and end-tidal CO2. TCD and NIRS CO2 reactivity indices were al-so extracted. Nimodipine significantly reduced ABP (11±13%) and increased heart rate, as well as NIRS oxygenation(6.0±4.8%) and blood volume indices (9.4±10.1%), while V(MCA) was not significantly decreased (2.0±3.5%). Nimodipine slightly but significantly reduced the V(MCA) response to changes in pCO2 whereas the CO2 reactivity of NIRS parameters was improved. The observed changes in cerebral tissue oxygenation and blood volume indicate nimodipine-induced cerebrovascular dilation and increased perfusion, while the effect on V(MCA)possibly results from dilation of the insonated artery. The present results cast doubt on the putative nimodipine-induced impairment of CO2 reactivity.

  9. Antioxidants prevent ethanol-induced contractions of canine cerebral vascular smooth muscle: relation to alcohol-induced brain injury.

    PubMed

    Li, W; Zheng, T; Altura, B T; Altura, B M

    2001-03-30

    The present study was designed to test the hypothesis that alpha-tocopherol (Vit. E) and pyrrolidine dithiocarbamate (PDTC) might exert direct effects on alcohol-induced contractions of canine basilar cerebral arteries. After precontraction of arterial ring segments with ethanol, PDTC (10(-8)-10(-6) M) and Vit. E (10(-6)-10(-4) M) induced concentration-dependent relaxations of cerebral arteries, compared to untreated controls. The effective concentrations producing approximately 50% of the maximal relaxation responses (EC(50) values) were about 2.48+/-0.09 x 10(-7) M for PDTC, and 1.87+/-0.10 x 10(-5) mM for Vit. E, respectively. Preincubation of these arterial rings with EC(50)'s of PDTC or Vit. E for 40 min attenuate markedly the contractions produced by alcohol, at concentrations of 1-400 mM. However, both PDTC and Vit.E do not relax equi-potent precontractions induced by either KCl or prostaglandin F(2alpha) (PGF(2alpha)) or inhibit their contractions. These data suggest that alcohol-induced contractions of cerebral arteries are mediated via excitation-contraction coupling pathways different from those used by KCl or receptor-mediated agonists such as PGF(2alpha). The present results, when viewed in light of other recently published data, suggest that antioxidants may prove useful in the amelioration and treatment of alcohol-induced brain damage and strokes.

  10. Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

    SciTech Connect

    Favelier, Sylvain; Boulin, Mathieu; Hamza, Samia; Cercueil, Jean-Pierre; Cherblanc, Violaine; Lepage, Come; Hillon, Patrick; Chauffert, Bruno; Krause, Denis; Guiu, Boris

    2013-08-01

    BackgroundThere is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin.MethodsIn 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated.ResultsPostembolization syndrome was observed after 30.9 % (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3-5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19 % (4 of 21) of patients. On imaging, no progression was encountered; four patients (24 %) exhibited stable disease, 12 (57 %) exhibited a partial response, and five (19 %) exhibited a complete response. Median TTTF was 16.7 months (Kaplan-Meier analysis). At 6 months, 94.7 % (95 % confidence interval [CI] 68.1-99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6 % (95 % CI 21.6-73.9) of patients at 1 year. Overall survival was 83.5 % (95 % CI 57-94.4) at 1 year.ConclusionIdarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.

  11. Triptan-induced Reversible Cerebral Vasoconstriction Syndrome: Two Case Reports with a Literature Review

    PubMed Central

    Kato, Yuji; Hayashi, Takeshi; Mizuno, Satoko; Horiuchi, Yohsuke; Ohira, Masayuki; Tanahashi, Norio; Takao, Masaki

    2016-01-01

    We encountered two patients with sumatriptan-induced reversible cerebral vasoconstriction syndrome (RCVS). The present patients were taking sumatriptan for the first time because they had been tentatively diagnosed with a migraine. On reviewing the literature, we found nine other cases of triptan-induced RCVS, predominantly among women aged 30 to 40 years. RCVS has been precipitated by triptan at the first ever use, after daily use, and even with long-term use at a normal dose. Patients with acute onset of severe headache should be thoroughly evaluated, and triptan should be administered appropriately. If triptan-induced RCVS is suspected, vascular imaging should be repeated after several days. PMID:27904122

  12. Cerebral blood oxygenation changes induced by visual stimulation in humans

    NASA Astrophysics Data System (ADS)

    Wenzel, Rudiger; Obrig, Hellmuth; Ruben, Jan; Villringer, Kersten; Thiel, Andreas; Bernarding, Johannes; Dirnagl, Ulrich; Villringer, Arno

    1996-10-01

    We examined local changes of cerebral oxygenation in response to visual stimuli by means of near infrared spectroscopy. A sharply outlined colored moving stimulus which is expected to evoke a broad activation of the striate and prestriate cortex was presented to sixteen healthy subjects. Six of these subjects were also exposed to a colored stationary and a gray stationary stimulus. In two subjects the colored moving stimulus was tested against the colored stationary with an optode position presumably over area V5/MT. As a control condition, subjects performed a simple finger opposition task. Since the calcarine fissure varies greatly with respect to bony landmarks, optodes were positioned individually according to 3D reconstructed magnetic resonance imaging (MRI). Concentration changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) were continuously monitored with a temporal resolution of 1 s, using an NIRO 500. In response to the visual stimulus, the grand average across all sixteen subjects resulted in a significant increase in oxy-Hb of 0.33 +/- 0.09 arbitrary units mirrored by a significant decrease in deoxy-Hb of -0.18 +/- 0.02 arbitrary units, while the motor control condition elicited no significant changes in any parameters. When the near infrared spectroscopy probes were positioned over area V5/MT, the drop of deoxy-Hb associated with the moving stimulus was significantly more pronounced than with the stationary stimulus in both subjects examined. No significant differences between the visual stimuli were observed at the optode position close to the calcarine fissure. The oxygenation changes observed in this study are consistent with the pattern we have reported for motor activation. They are in line with physiological considerations and functional MRI studies relying on blood oxygenation level-dependent contrast.

  13. Alleviation of Brain Injury-Induced Cerebral Metabolic Depression by Amphetamine: A Cytochrome Oxidase Histochemistry Study

    PubMed Central

    Sutton, Richard L.; Hovda, David A.; Chen, Michael J.; Feeney, Dennis M.

    2000-01-01

    Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and ,he administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of II subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilaterai to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans. PMID:10709218

  14. Inhibition of cerebral ischemia/reperfusion injury-induced apoptosis: nicotiflorin and JAK2/STAT3 pathway

    PubMed Central

    Hu, Guang-qiang; Du, Xi; Li, Yong-jie; Gao, Xiao-qing; Chen, Bi-qiong; Yu, Lu

    2017-01-01

    Nicotiflorin is a flavonoid extracted from Carthamus tinctorius. Previous studies have shown its cerebral protective effect, but the mechanism is undefined. In this study, we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway. The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion. Nicotiflorin (10 mg/kg) was administered by tail vein injection. Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining. Additionally, p-JAK2, p-STAT3, Bcl-2, Bax, and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay. Nicotiflorin altered the shape and structure of injured neurons, decreased the number of apoptotic cells, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax, decreased Bax immunoredactivity, and increased Bcl-2 protein expression and immunoreactivity. These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway. PMID:28250754

  15. Neuroprotective activity of Wedelia calendulacea on cerebral ischemia/reperfusion induced oxidative stress in rats

    PubMed Central

    Prakash, Tigari; Kotresha, Dupadahalli; Nedendla, Rama Rao

    2011-01-01

    Objective: This study was undertaken to evaluate the neuroprotective activity of Wedelia calendulacea against cerebral ischemia/reperfusion induced oxidative stress in the rats. Materials and Methods: The global cerebral ischemia was induced in male albino Wistar rats by occluding the bilateral carotid arteries for 30 min followed by 1 h and 4 h reperfusion. At various times of reperfusion, the histopathological changes and the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione–s–transferase (GST), and hydrogen peroxide (H2O2) activity and brain water content were measured. Results: The ischemic changes were preceded by increase in concentration of MDA, hydrogen peroxide and followed by decreased GPx, GR, and GST activity. Treatment with W. calendulacea significantly attenuated ischemia–induced oxidative stress. W. calendulacea administration markedly reversed and restored to near normal level in the groups pre-treated with methanolic extract (250 and 500 mg/kg, given orally in single and double dose/day for 10 days) in dose-dependent way. Similarly, W. calendulacea reversed the brain water content in the ischemia reperfusion animals. The neurodegenaration also conformed by the histopathological changes in the cerebral-ischemic animals. Conclusion: The findings from the present investigation reveal that W. calendulacea protects neurons from global cerebral–ischemic injury in rat by attenuating oxidative stress. PMID:22144773

  16. Ganzfeld-induced hallucinatory experience, its phenomenology and cerebral electrophysiology.

    PubMed

    Wackermann, Jirí; Pütz, Peter; Allefeld, Carsten

    2008-01-01

    Ganzfeld, i.e., exposure to an unstructured, uniform stimulation field, elicits in most observers pseudo-hallucinatory percepts, and may even induce global functional state changes ('altered states of consciousness'). The present paper gives a comprehensive overview of the phenomenology of subjective experience in the ganzfeld and its electrophysiological correlates. Laboratory techniques for visual or multi-modal ganzfeld induction are explained. The spectrum of ganzfeld-induced phenomena, ranging from elementary percepts to complex, vivid, dream-like imagery is described, and the latter illustrated by transcripts of subjects' reports. Similarities and differences to related sensory/perceptual phenomena are also discussed. Earlier findings on electrophysiological correlates of the ganzfeld are reviewed. Our own studies of electroencephalographic (EEG) activity in the ganzfeld are presented in some detail, and a re-analysis of data on EEG correlates of hallucinatory percepts in statu nascendi is reported. The results do not support the hypothesis of the hypnagogic origin of the percepts; the ganzfeld-induced steady-state is an activated state, and the spectral EEG dynamics in the alpha frequency range reveals processes of attention shifts and percept formation. The final section is devoted to the controversial topic of allegedly anomalous communication between human subjects ('ganzfeld telepathy'). It is shown that the use of ganzfeld in this research field relies partly on unsupported hypotheses concerning ganzfeld-induced states, partly on a weak conceptual background of the experimental procedure. The rôle of a particular belief system shared by the participants and experimenters is critically discussed.

  17. Effect of siRNA‑induced inhibition of IL‑6 expression in rat cerebral gliocytes on cerebral edema following traumatic brain injury.

    PubMed

    Xu, Bin; Yu, Dong-Ming; Liu, Fu-Sheng

    2014-10-01

    The present study aimed to investigate the effect of RNA interference (RNAi) on the inhibition of interleukin (IL)‑6 expression in rat cerebral gliocytes in vitro and rat cerebral traumatic tissues in vivo, as well as the effect of RNAi on cerebral edema. pSUPER vectors containing IL‑6 small hairpin RNA (pSUPER‑IL‑6 1‑5) were designed, constructed and transfected into C6 rat glioma cells using cationic liposomes. ELISA was used to select the plasmid with the strongest interference effect. A freefall method was used to generate a rat brain injury model and rats were randomly divided into treatment, empty plasmid and control groups (n=14/group). IL‑6 levels, water content and sodium content were determined in the brain tissues at 24 and 72 h post‑injury. pSUPER‑IL‑6 was effectively transfected into C6 cells and was found to inhibit the expression of IL‑6 rather than IL‑8. The pSUPER‑IL‑6 1 vector was most effective in inducing RNAi. In vivo, IL‑6 levels were observed to be lowest in the interference group and there were statistically significant differences in water and sodium content among the experimental groups (P<0.05). RNAi was found to inhibit IL‑6 expression in vivo and in vitro in rat cerebral gliocytes, and the reduction of the IL‑6 levels was found to reduce post‑traumatic cerebral edema.

  18. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    PubMed Central

    2010-01-01

    Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

  19. Prolactin protects against the methamphetamine-induced cerebral vascular toxicity.

    PubMed

    Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Ali, Syed F; Gonzalez, Carmen

    2013-11-01

    Methamphetamine (Meth) is a highly addictive drug of abuse which alters the dopaminergic system and damages the blood-brain barrier (BBB), structure that protects the brain tissue from the circulating substances in the blood, keeping a low permeability through the presence of tight junctions (TJs) between endothelial cells. Meth increases BBB permeability by decreasing the TJs proteins claudin-5 and occludin and by decreasing the viability of endothelial cells. Individuals abused of Meth have increased blood concentrations of prolactin (PRL); hormone related with milk production, but able to increase the expression of TJs proteins and to decrease permeability on the mammary epithelium and brain endothelial cells. However, the effects of PRL on the permeability of the BBB in the presence of Meth have not been studied. Here, we report Meth-induced apoptosis and decreased cellular proliferation as well as the trans-endothelial electrical resistance (TEER), related to a decrease of claudin-5 and occludin in primary cultured bovine brain microvessel endothelial cells. The expression of the PRL receptor was not altered. Administration of PRL prevented a decrease in cellular proliferation, an increase in apoptosis and restored the TEER and TJs proteins to basal levels. This protection was absent at high Meth concentrations. These data suggest that PRL protects brain endothelial cells against the Meth-induced toxicity. Further investigation is required to study the mechanisms involved and to confirm these effects in vivo.

  20. Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla.

    PubMed

    Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P

    2007-03-01

    Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.

  1. Radiation-induced cerebral meningioma: a recognizable entity.

    PubMed

    Rubinstein, A B; Shalit, M N; Cohen, M L; Zandbank, U; Reichenthal, E

    1984-11-01

    The authors retrospectively analyzed the clinical and histopathological findings in 201 patients with intracranial meningiomas operated on in the period 1978 to 1982. Forty-three of the patients (21.4%) had at some previous time received radiation treatment to their scalp, the majority for tinea capitis. The findings in these 43 irradiated patients were compared with those in the 158 non-irradiated patients. Several distinctive clinical and histological features were identified in the irradiated group, which suggest that radiation-induced meningiomas can be defined as a separate nosological subgroup. The use of irradiation in large numbers of children with tinea capitis in the era prior to the availability of griseofulvin may be responsible for a significantly increased incidence of intracranial meningiomas.

  2. An Experimental Model of Vasovagal Syncope Induces Cerebral Hypoperfusion and Fainting-Like Behavior in Awake Rats

    PubMed Central

    McBride, Devin W.; Reis, Cesar; Frank, Ethan; Klebe, Damon W.; Zhang, John H.; Applegate, Richard

    2016-01-01

    Vasovagal syncope, a contributing factor to elderly falls, is the transient loss of consciousness caused by decreased cerebral perfusion. Vasovagal syncope is characterized by hypotension, bradycardia, and reduced cerebral blood flow, resulting in fatigue, altered coordination, and fainting. The purpose of this study is to develop an animal model which is similar to human vasovagal syncope and establish an awake animal model of vasovagal syncope. Male Sprague-Dawley rats were subjected to sinusoidal galvanic vestibular stimulation (sGVS). Blood pressure, heart rate, and cerebral blood flow were monitored before, during, and post-stimulation. sGVS resulted in hypotension, bradycardia, and decreased cerebral blood flow. One cohort of animals was subjected to sGVS while freely moving. sGVS in awake animals produced vasovagal syncope-like symptoms, including fatigue and uncoordinated movements; two animals experienced spontaneous falling. Another cohort of animals was preconditioned with isoflurane for several days before being subjected to sGVS. Isoflurane preconditioning before sGVS did not prevent sGVS-induced hypotension or bradycardia, yet isoflurane preconditioning attenuated sGVS-induced cerebral blood flow reduction. The sGVS rat model mimics elements of human vasovagal syncope pathophysiology (hypotension, bradycardia, and decreased cerebral perfusion), including behavioral symptoms such as fatigue and altered balance. This study indicates that the sGVS rat model is similar to human vasovagal syncope and that therapies directed at preventing cerebral hypoperfusion may decrease syncopal episodes and reduce injuries from syncopal falls. PMID:27658057

  3. Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes.

    PubMed

    Li, Jianfeng; Su, Jialin; Li, Wenyan; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-10-30

    Considerable evidence is accumulating to suggest that in vivo formation of free radicals in the brain, such as peroxynitrite (ONOO-), and programmed cell death (i.e. apoptosis) play important roles in neurodegeneration and stroke. However, it is not known whether ONOO- can induce apoptosis in cerebral vascular smooth muscle cells (CVSMCs). The present study was designed to determine whether or not canine CVSMCs undergo apoptosis following treatment with ONOO-. Direct exposure of canine CVSMCs to ONOO- induced apoptosis in a concentration-dependent manner, as confirmed by means of fluorescence staining, TdT-mediated dUTP nick-end labeling and comet assays. Peroxynitrite treatment resulted in an elevation of [Ca2+]i in the CVSMCs. Peroxynitrite-induced apoptosis may thus be brought about by activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis need to be further investigated, the present findings could be used to suggest that ONOO- formation in the brain may play important roles in neurodegenerative processes and strokes via detrimental actions on cerebral microvessels and blood flow.

  4. Behavior of Lipiodol Markers During Image Guided Radiotherapy of Bladder Cancer

    SciTech Connect

    Chai Xiangfei; Herk, Marcel van; Kamer, Jeroen B. van de; Remeijer, Peter; Bex, Axel; Betgen, Anja; De Reijke, Theo M.; Hulshof, Maarten C.C.M.; Pos, Floris J.; Bel, Arjan

    2010-05-01

    Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers. Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV). Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 +- 1.1 cm{sup 3}. The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs. Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones.

  5. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

    PubMed Central

    Saxena, Anil Kumar; Abdul-Majeed, Saif Saad; Gurtu, Sunil; Mohamed, Wael M.Y.

    2015-01-01

    Aging related reduction in cerebral blood flow (CBF) has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO) in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult. PMID:26937356

  6. Curcumin attenuates the middle cerebral artery occlusion-induced reduction in γ-enolase expression in an animal model

    PubMed Central

    Gim, Sang-Ah; Lee, So-Ra; Shah, Fawad-Ali

    2015-01-01

    Curcumin exerts a protective effect in cerebral ischemia through its anti-oxidant and anti-inflammatory activities. γ-enolase is a glycolytic enzyme expressed in neurons that is known to exerts a neuroprotective effect. We investigated whether curcumin regulates γ-enolase expression in focal cerebral ischemic injury in rats. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia. Adult male rats were injected intraperitoneally with either vehicle or curcumin (50 mg/kg) 1 h after MCAO and cerebral cortex tissues were isolated 24 h after MCAO. We found that MCAO-induced injury resulted in a reduction in γ-enolase expression in vehicle-treated animals using a proteomics approach. However, this reduction was attenuated in animals with MCAO treated with curcumin. Reverse-transcription PCR and Western blot analyses also showed that curcumin treatment prevented the MCAO injury-induced reduction in γ-enolase expression. The results of this study suggest that curcumin exerts its neuroprotective function in focal cerebral ischemia by regulating the expression of γ-enolase. PMID:26755923

  7. Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia.

    PubMed

    Molnár, A H; Varga, C; Berkó, A; Rojik, I; Párducz, A; László, F; László, F A

    2008-03-01

    The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

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

    PubMed

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

    2014-03-01

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

  9. In vivo photoacoustic tomography of mouse cerebral edema induced by cold injury

    NASA Astrophysics Data System (ADS)

    Xu, Zhun; Zhu, Quing; Wang, Lihong V.

    2011-06-01

    For the first time, we have implemented photoacoustic tomography (PAT) to image the water content of an edema in vivo. We produced and imaged a cold-induced cerebral edema transcranially, then obtained blood vessel and water accumulation images at 610 and 975 nm, respectively. We tracked the changes at 12, 24, and 36 h after the cold injury. The blood volume decreased after the cold injury, and the maximum area of edema was observed 24 h after the cold injury. We validated PAT of the water content of the edema through magnetic Resonance Imaging and the water spectrum from the spectrophotometric measurement.

  10. Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus.

    PubMed

    Stanojlović, Miloš; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zlatković, Jelena; Horvat, Anica; Drakulić, Dunja

    2016-08-01

    Although a substantial number of pre-clinical and experimental studies have investigated effects of 17β-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 μg/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-κB, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-κB with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17β-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17β-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17β-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.

  11. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion.

    PubMed

    Leardini-Tristão, Marina; Borges, Juliana Pereira; Freitas, Felipe; Rangel, Raquel; Daliry, Anissa; Tibiriçá, Eduardo; Estato, Vanessa

    2017-02-15

    The therapeutic potential of early exercise training following cerebral hypoperfusion was investigated on brain perfusion and inflammation in rats with permanent bilateral occlusion of the common carotid arteries (2VO). Wistar rats were subjected to 2VO or sham surgery and each group was then subdivided randomly into sedentary or exercise groups. Early exercise training was initiated after three days of 2VO or sham surgery and consisted of seven days of treadmill training (30min/day at ∼60% of maximal exercise test), composing four groups: 1) Sham sedentary (Sham-Sed), 2) Sham exercised (Sham-Ex), 3) 2VO sedentary (2VO-Sed) and 4) 2VO exercised (2VO-Ex). Microvascular cerebral blood flow (MCBF) and NADPH oxidase and eNOS gene expression were evaluated by laser speckle contrast imaging and RT-PCR, respectively, and brain functional capillary density and endothelial-leukocyte interactions were evaluated by fluorescence intravital video-microscopy. The 2VO-Sed group presented a decrease in MCBF (Sham-Sed: 230.9±12.2 vs. 2VO-Sed: 183.6±10.6 arbitrary perfusion units, P<0.05) and in functional capillary density (Sham-Sed: 336.4±25.3 vs. 2VO-Sed: 225.5±28.1capillaries/mm(2), P<0.05). Early intervention with physical exercise was able to prevent the cerebral microvascular inflammation by decreasing endothelial-leukocyte interactions (2VO-Ex: 0.9±0.3 vs. 2VO-Sed: 5±0.6cells/min/100μm, P<0.0001) and reducing brain NADPH oxidase gene expression (2VO-Ex: 1.7±0.1 arbitrary units, P<0.05). Cerebral microcirculatory and inflammatory alterations appear to be triggered during the first days after 2VO surgery, and early intervention with physical exercise may represent a means of preventing the microvascular alterations induced by chronic cerebral hypoperfusion.

  12. Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.

    PubMed

    Yepes, M; Wu, F; Torre, E; Cuellar-Giraldo, D; Jia, D; Cheng, L

    2016-04-05

    The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein βII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the endocytic zone. In summary, the data presented here indicate that following the exocytotic release of neurotransmitters tPA activates the mechanism whereby SVs are retrieved from the presynaptic membrane and endocytosed to replenish the pool of vesicles available for a new cycle of exocytosis. Together, these results indicate that in murine cerebral cortical neurons tPA plays a central role coupling SVs exocytosis and endocytosis.

  13. Efficacy of Rho kinase inhibitor on cognitive impairment induced by chronic cerebral hypoperfusion in rats

    PubMed Central

    Zhang, Qiang; Zhang, Jun-Jian; Han, Zhong-Mou

    2015-01-01

    This work aims to explore the efficacy of Rho kinase inhibitor Fasudil on cognitive impairment induced by chronic cerebral hypoperfusion in rats. A total of 32 male adult Sprague Dawley (SD) rats were randomly divided into three groups: treatment group, control group and sham-operated group for severe carotid artery stenosis model. After two weeks, 8.35 mg/kg Fasudil and physiological saline were intraperitoneally applied twice per day in treatment group and control group, respectively. Morris water maze test was performed in each group to detect the changes of cognitive function and observe the hippocampal pathomorphology in rats after eight weeks. The average escape latency distinctly shortened (P < 0.01) and the percentage of swimming distance in the platform quadrant significantly increased (P < 0.01) in treatment group compared with those at corresponding time points in control group. The rate of carotid artery stenosis in rats had no statistical difference between treatment and control groups (P > 0.05). Fasudil effectively improved hippocampal pathomorphology. Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats. PMID:25932185

  14. CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

    PubMed

    Qiu, Bin; Hu, Shengdi; Liu, Libing; Chen, Man; Wang, Lai; Zeng, Xianwei; Zhu, Shigong

    2013-07-12

    Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way.

  15. Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action.

    PubMed

    Li, Jianfeng; Li, Wenyan; Altura, Bella T; Altura, Burton M

    2004-04-01

    The present study was undertaken to determine the vascular actions of peroxynitrite (ONOO(-)), the product of superoxide and nitric oxide (NO), in isolated canine cerebral arteries and to gain insight into its potential mechanisms of action. In the absence of any vasoactive agent, ONOO(-) (from 10(-7) to 10(-6) M) was able to reduce the basal tension. In prostaglandin F2alpha-precontracted canine basilar arterial rings, ONOO(-) elicited concentration-dependent relaxation at concentrations from 10(-8) to 10(-5) M. The effective concentrations producing approximately 50% maximal relaxation (EC(50)) to ONOO(-) were 4.06 x 10(-6) and 4.12 x 10(-6) M in intact and denuded rings, respectively (P > 0.05). No significant differences in relaxation responses were found in ring preparations with or without endothelium (P > 0.05). The presence of either 5 microM methylene blue (MB) or 5 microM 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO(-). Tetraethylammonium chloride (T-2265) significantly decreased the ONOO(-)-induced relaxations in a concentration-dependent manner. However, ONOO(-) had no effect on rings precontracted by high KCL (P > 0.05). Addition of low concentrations of calyculin A (50 nM) was able to abolish the ONOO(-)-induced relaxation. Furthermore, ONOO(-) significantly inhibited calcium-induced contractions of K(+)-depolarized canine cerebral rings in a concentration-related manner. Lastly, a variety of pharmacological agents and antagonists including L-NMMA, l-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, etc., did not influence the relaxant effects of ONOO(-) on the rings. Our new results suggest that ONOO(-)-triggered relaxation, on canine cerebral arteries, is mediated by elevation of cyclic guanosine monophosphate (cGMP) levels, membrane hyperpolarization via K+ channel activation, activation of myosin light chain phosphatase activity, and

  16. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    PubMed

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

  17. Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

    PubMed

    Wisor, J P; Morairty, S R; Huynh, N T; Steininger, T L; Kilduff, T S

    2006-08-11

    Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

  18. ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia.

    PubMed

    Zhang, Meijuan; Li, Wenjin; Niu, Guangming; Leak, Rehana K; Chen, Jun; Zhang, Feng

    2013-01-01

    Ischemic stroke is a devastating condition lacking effective therapies. A promising approach to attenuate ischemic injury is mild hypothermia. Recent studies show that adenosine nucleotides can induce hypothermia in mice. The purpose of the present study was to test the hypothesis that adenosine 5'-triphosphate (ATP) induces mild hypothermia in rats and reduces ischemic brain injury. We found that intraperitoneal injections of ATP decreased core body temperature in a dose-dependent manner; the dose appropriate for mild hypothermia was 2 g/kg. When ATP-induced hypothermia was applied to stroke induced by middle cerebral artery occlusion, however, a neuroprotective effect was not observed. Instead, the infarct volume grew even larger in ATP-treated rats. This was accompanied by an increased rate of seizure events, hemorrhagic transformation, and higher mortality. Continuous monitoring of physiologic parameters revealed that ATP reduced heartbeat rate and blood pressure. ATP also increased blood glucose, accompanied by severe acidosis and hypocalcemia. Western blotting showed that ATP decreased levels of both phospho-Akt and total-Akt in the cortex. Our results reveal that, despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke. Instead, we show for the first time that ATP treatment is associated with exaggerated ischemic outcomes and dangerous systemic side effects.

  19. Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM.

    PubMed

    Watson, C S; White, S E; Homan, J H; Kimura, K A; Brien, J F; Fraher, L; Challis, J R; Bocking, A D

    1999-04-01

    Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2 has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2 concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained from the fetal parietal cortex over 70 h after surgery to determine steady-state extracellular fluid adenosine and PGE2 concentrations. On each of postoperative days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the fetus was monitored for a further 11 h with 30-min dialysate samples collected throughout. Immediately after surgery, dialysate PGE2 and adenosine concentrations were 3.7 +/- 0.7 and 296 +/- 127 nM, respectively. PGE2 did not change over the 70 h, whereas adenosine decreased to 59 +/- 14 nM (P < 0.05) at 4 h and then remained unchanged. Ethanol decreased dialysate PGE2 concentration for 2 h (3.3 +/- 0.3 to 1.9 +/- 0.4 nM; P < 0.05) and increased adenosine concentration for 6 h (87 +/- 13 to a maximum of 252 +/- 59 nM, P < 0.05). Ethanol decreased FBM incidence from 47 +/- 7 to 16 +/- 5% (P < 0.01) for 8 h. Saline infusion did not change dialysate adenosine or PGE2 concentrations or FBM incidence. These data are consistent with the hypothesis that fetal cerebral adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of FBM at 123 days of gestation in sheep.

  20. Chrysin improves cognitive deficits and brain damage induced by chronic cerebral hypoperfusion in rats.

    PubMed

    He, Xiao-Li; Wang, Yue-Hua; Bi, Ming-Gang; Du, Guan-Hua

    2012-04-05

    Chronic cerebral hypoperfusion, induced by permanent occlusion of bilateral common carotid arteries (2VO), is related to neurological disorders and contributes to cognitive decline. Chrysin (5,7-dihydroxyflavone) is an important member of the flavonoid family. The aim of this study is to investigate the effects of chrysin on cognitive deficits and brain damage in this rat 2VO model. At 52days after ligation, the escape latency in Morris water maze was significantly increased in rats subjected to 2VO, the neuronal damage was also increased accompanied by a large proliferation in glial fibrillary acidic protein (GFAP) immunoreactivity with marked white matter lesions, and neuronal cell apoptosis, all of which were significantly alleviated by long treatment of chrysin (30mg/kg). Biochemical examinations revealed that chrysin decreased lipid peroxide, reduced the increased activities of superoxide dismutase, and attenuated the decreased activities of glutathione peroxidase in 2VO rats. The results suggest that chrysin may have therapeutic potential for the treatment of neurodegeneration and dementia caused by decreased cerebral blood flow, which is most likely related, at least in part, to its anti-inflammatory and antioxidant properties.

  1. Microglial reaction in focal cerebral ischaemia induced by intra-carotid homologous clot injection.

    PubMed

    Ng, Y K; Ling, E A

    2001-01-01

    This study examined the microglial reaction in a simulated thrombo-embolus ischaemia in rats given an intracarotid injection of a suspension of homologous blood clot. All rats including the controls receiving vehicle injection were perfused at 5 hours, and 1, 3 and 7 days post-operation. The brains were removed and processed for immunohistochemistry using a panel of monoclonal antibodies: OX-42, OX-18 and OX-6 for labeling of microglia. In rats given saline injection OX-42 immunoreactive microglial cells were observed to be distributed quite evenly throughout the whole brain. When injection of clot suspension was given, microglial cells responded vigorously, particularly in the ipsilateral hippocampus. Microglial reaction was also detected in the ipsilateral cerebral cortex, caudate as well as septal nuclei. The majority of the detected reactive microglial cells were hypertrophied showing thick or stout processes. Some rod-like and amoeboid microglia were also observed. Rarely did the reactive microglia express OX-6 immunoreactivity. All microglial cells were unreactive for OX-18. The actual mechanisms leading to the microglial activation as well as functions of reactive microglia in focal cerebral ischaemia remain speculative. In the absence of direct evidence, it could only be suggested that they may act as sensor cells for detection of subtle alterations in the microenvironment, probably in response to focal ischaemia and/or leakage of serum-derived factors induced by thrombo-embolus stroke.

  2. In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice.

    PubMed

    Ling, Wenting; Endo, Toshihiro; Kubo, Ken-Ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2016-01-01

    Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner.

  3. Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

    PubMed Central

    Ma, Jianhua; Zhang, Maoying; Li, Shaowu; Wu, Bingshan; Nie, Xiaohu; Jiao, Jiao; Zhao, Hao; Wang, Shanshan; Yang, Yuanyuan; Zhang, Yesen; Sun, Yilin; Wicha, Max S.; Chang, Alfred E.; Gao, Shaorong; Li, Qiao; Xu, Ruxiang

    2015-01-01

    Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells. PMID:26352672

  4. In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice

    PubMed Central

    Ling, Wenting; Endo, Toshihiro; Kubo, Ken-ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2016-01-01

    Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner. PMID:26869994

  5. Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice.

    PubMed

    Sugimori, Hiroshi; Yao, Hiroshi; Ooboshi, Hiroaki; Ibayashi, Setsuro; Iida, Mitsuo

    2004-08-01

    Recent advances in genetical engineering of the mouse have highlighted the importance of reproducible and less invasive models of cerebral ischemia in mice. In this paper, we developed minimally invasive and reproducible model of distal middle cerebral artery (MCA) occlusion in mice using krypton (Kr) laser-induced photothrombosis. C57BL/6 or BALB mice (n=8 each) were anesthetized with halothane. The skin was cut, the temporal muscle was retracted, and the right distal MCA was observed through the skull. A Kr laser beam of wavelength 568 nm was focused onto the MCA over the intact skull. Upon laser irradiation, intravenous administration of a rose bengal solution was begun. After 4 min of irradiation, the laser beam was refocused on the MCA just proximal to the first spot, and another 4-min irradiation was performed. Then, the right common carotid artery (CCA) was ligated. Three days later, the brain was removed, and infarct volume was determined. Infarction confined almost solely to the cortical area was produced in each mouse. Mean infarct volume in C57BL/6 mice was 25.2+/-13.7 mm3. The BALB mice group showed significantly larger and more reproducible infarction (44.1+/-5.2 mm3; the coefficient of variation was 12%) than did C57BL/6 mice (P<0.005). Our photothrombosis model of stroke in mice can be performed without craniectomy, and its reproducibility is satisfactory when using BALB mice.

  6. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    NASA Astrophysics Data System (ADS)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  7. Neuroprotective effects of Tilia americana var. mexicana on damage induced by cerebral ischaemia in mice.

    PubMed

    Angeles-López, Guadalupe E; González-Trujano, Ma Eva; Gómez, Claudia; Chánez-Cárdenas, Ma Elena; Ventura-Martinez, Rosa

    2016-09-01

    Tilia americana var. mexicana (T. americana) is a plant widely used in Mexico for its medicinal properties on the central nervous system. In the present study, we designed a protocol to investigate the neuroprotective effects of non-polar and polar extracts of T. americana on damage induced by cerebral ischaemia in mice. Vehicle or extracts were administered immediately after ischaemia. Functional neurological deficit, survival percentage and infarct area were determined in each experimental group. Results showed that groups treated with non-polar or polar extracts of T. americana had increased survival rate, improved neurological deficits and diminished the infarct area in relation to the ischaemic group. In conclusion, this study confirms the neuroprotective activity of T. americana, suggests a possible synergism between non-polar and polar constituents and supports its potential as a useful aid in the clinical management of stroke.

  8. Antioxidants prevent depletion of [Mg2+]i induced by alcohol in cultured canine cerebral vascular smooth muscle cells: possible relationship to alcohol-induced stroke.

    PubMed

    Li, W; Zheng, T; Altura, B T; Altura, B M

    2001-07-01

    Low serum concentrations of Mg(2+) ions have been reported, recently, in patients with coronary disease, atherosclerosis, and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [alpha-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Mg(2+) ([Mg(2+)](i)) depletion associated with cerebral vascular injury induced by alcohol. Exposure of cultured canine cerebral vascular smooth muscle cells to alcohol (10-100 mM) for 24 h induced marked depletion in [Mg(2+)](i) (i.e., approximately 30-65%, depending upon alcohol concentration). Treatment of the cultured cells with either PDTC (0.1 microM) or alpha-tocopherol (15 microM) for 24 h, alone, failed to interfere with basal [Mg(2+)](i) levels. However, preincubation of the cells with either alpha-tocopherol or PDTC for 24 h completely inhibited the depletion of [Mg(2+)](i) induced by exposure to 10-100 mM ethanol. These results indicate that alpha-tocopherol and PDTC prevent decreases in [Mg(2+)](i) produced by ethanol. Moreover, these new results suggest that such protective effects of alpha-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in prevention and amelioration of cerebral vascular injury and stroke in alcoholics.

  9. Citrulline uptake in rat cerebral cortex slices: modulation by Thioacetamide -Induced hepatic failure.

    PubMed

    Zielińska, Magdalena; Obara-Michlewska, Marta; Hilgier, Wojciech; Albrecht, Jan

    2014-12-01

    L-citrulline (Cit) is a co-product of NO synthesis and a direct L-arginine (Arg) precursor for de novo NO synthesis. Acute liver failure (ALF) is associated with increased nitric oxide (NO) and cyclic GMP (cGMP) synthesis in the brain, indirectly implicating a role for active transport of Cit. In the present study we characterized [(3)H]Cit uptake to the cortical brain slices obtained from control rats and rats with thioacetamide (TAA)-induced ALF ("TAA slices"). In both control and TAA slices the uptake was partially Na(+)-dependent and markedly inhibited by substrates of systems L and N, including L-glutamine (Gln), which accumulates in excess in brain during ALF. Cit uptake was not affected by Arg, the y(+)/y(+)L transport system substrate, nor by amino acids taken up by systems A, xc (-)or XAG. The Vmax of the uptake in TAA slices was ~60 % higher than in control slices. Chromatographic (HPLC) analysis revealed a ~30 % increase of Cit concentration in the cerebral cortical homogenates of TAA rats. The activity of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL), the two enzymes of Cit-NO cycle catalyzing synthesis of Arg, showed an increase in TAA rats, consistent with increased ASS and ASL protein expression, by ~30 and ~20 %, respectively. The increased Cit-NO cycle activity was paralleled by increased expression of mRNA coding for inducible nitric oxide synthase (iNOS). Taken together, the results suggest a role for Cit in the activation of cerebral NO synthesis during ALF.

  10. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    PubMed Central

    Yang, Ying; Ju, Jieyang; Deng, Min; Wang, Jing; Liu, Hui; Xiong, Li; Zhang, Junjian

    2017-01-01

    Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs), were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit. PMID:28106731

  11. Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role of extracellular and intracellular calcium ions.

    PubMed

    Li, Wenyan; Li, Jianfeng; Liu, Weiming; Altura, Bella T; Altura, Burton M

    2004-01-16

    Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10, 25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical characteristics of nuclear shrinkage, condensation, and DNA breakage as well as formation of apoptotic bodies observed by fluorescence staining, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet assays. Such effects of alcohol on cerebral VSMCs were time- and concentration-dependent. The threshold ethanol concentration for induction of the apoptotic process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators, i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM) and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6) M), respectively, ameliorated greatly the number of cerebral VSMCs which underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may contribute to alcohol-induced brain-vascular damage and stroke. In addition, our findings point to potential caution for humans who imbibe two or more standard drinks per day or who undergo 'binge drinking'.

  12. Quantitative analysis of iron concentration and expression of ferroportin 1 in the cortex and hippocampus of rats induced by cerebral ischemia.

    PubMed

    Li, Lin; Li, Yan-wei; Zhao, Jin-ying; Liu, Yue-Ze; Holscher, Christian

    2009-11-01

    Iron overload induced by brain ischemia has been shown to be involved in neurodegenerative disease. Little is known about the relationship between brain ischemia and ferroportin 1 (FP1). The aims of this study are: (i) to determine whether iron accumulation in the brain is induced by cerebral hypoperfusion; and (ii) to test whether expression of FP1 is influenced by cerebral ischemia. The common carotid arteries (CCA) of rats were ligated bilaterally to induce cerebral ischemia, and the iron concentration of the cortex and hippocampus was measured by graphite furnace atomic absorption spectrometry. Iron was stained by Perl's method. The expression of FP1 mRNA and protein was shown by the reverse transcriptase polymerase chain reaction and immunohistochemical methods. The iron concentration in the cortex and hippocampus of ischemic rats had increased on day 7 (CCA7) and significantly on day 28 (CCA28) compared to control rats. More iron granules had been deposited in the cerebral cortex and hippocampus in rats with bilaterally ligated CCA on CCA7 and CCA28. In ischemic rats, FP1 expression in the cerebral cortex and hippocampus was decreased by CCA7 and this was more marked by CCA28 compared to control rats. We therefore concluded that iron deposition in the cerebral cortex and hippocampus of rats is induced by cerebral ischemia. Iron deposition may be attributed to the decrease in FP1 expression, and this inhibition of FP1 expression could be a major contributor to the formation of iron deposits in cerebral ischemia.

  13. Hydrogen peroxide induces apoptosis in cerebral vascular smooth muscle cells: possible relation to neurodegenerative diseases and strokes.

    PubMed

    Li, Jianfeng; Li, Wenyan; Su, Jialin; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-12-15

    Recently, reactive oxygen species (ROS) have been suggested as important mediators of brain damage in a number of disease states, including traumatic brain injury, neurodegenerative diseases and strokes. Apoptosis has been suggested to play an important role in neurodegenerative diseases, traumatic brain injury and strokes. The aim of this study was to determine whether or not cerebral vascular smooth muscle cells (CVSMCs) undergo apoptosis following treatment with hydrogen peroxide (H2O2). Herein, we demonstrate, for the first time, that H2O2 can induce apoptosis in a concentration-dependent manner in primary cultured CVSMCs, as measured by several morphological and biochemical criteria. H2O2-induced apoptosis may be initiated by stimulating Ca2+-dependent endonuclease activity. The present new data suggest that apoptosis in cerebral VSMCs, induced by ROS, such as H2O2, could play important roles in neruodegenerative processes, traumatic brain injury and strokes.

  14. Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure.

    PubMed

    Panerai, R B; Dawson, S L; Eames, P J; Potter, J F

    2001-05-01

    The influence of different types of maneuvers that can induce sudden changes of arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response was studied in 56 normal subjects (mean age 62 yr, range 23-80). ABP was recorded in the finger with a Finapres device, and bilateral recordings of CBFV were performed with Doppler ultrasound of the middle cerebral arteries. Recordings were performed at rest (baseline) and during the thigh cuff test, lower body negative pressure, cold pressor test, hand grip, and Valsalva maneuver. From baseline recordings, positive and negative spontaneous transients were also selected. Stability of PCO2 was monitored with transcutaneous measurements. Dynamic autoregulatory index (ARI), impulse, and step responses were obtained for 1-min segments of data for the eight conditions by fitting a mathematical model to the ABP-CBFV baseline and transient data (Aaslid's model) and by the Wiener-Laguerre moving-average method. Impulse responses were similar for the right- and left-side recordings, and their temporal pattern was not influenced by type of maneuver. Step responses showed a sudden rise at time 0 and then started to fall back to their original level, indicating an active autoregulation. ARI was also independent of the type of maneuver, giving an overall mean of 4.7 +/- 2.9 (n = 602 recordings). Amplitudes of the impulse and step responses, however, were significantly influenced by type of maneuver and were highly correlated with the resistance-area product before the sudden change in ABP (r = -0.93, P < 0.0004). These results suggest that amplitude of the CBFV step response is sensitive to the point of operation of the instantaneous ABP-CBFV relationship, which can be shifted by different maneuvers. Various degrees of sympathetic nervous system activation resulting from different ABP-stimulating maneuvers were not reflected by CBFV dynamic autoregulatory responses within the physiological range of ABP.

  15. Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy

    PubMed Central

    Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.

    2016-01-01

    Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with

  16. Paradoxical Air Microembolism Induces Cerebral Bioelectrical Abnormalities and Occasionally Headache in Patent Foramen Ovale Patients With Migraine

    PubMed Central

    Sevgi, Eser Başak; Erdener, Sefik Evren; Demirci, Mehmet; Topcuoglu, Mehmet Akif; Dalkara, Turgay

    2012-01-01

    Background Although controversial, paradoxical embolism via patent foramen ovale (PFO) may account for some of the migraine attacks in a subset of migraine with aura (MA) patients. Induction of MA attacks with air bubble injection during transcranial Doppler ultrasound in MA patients with PFO supports this view. It is likely that cerebral embolism in patients with right-to-left shunt induces bioelectrical abnormalities to initiate MA under some conditions. Methods and Results We investigated changes in cerebral bioelectrical activity after intravenous microbubble injection in 10 MA patients with large PFO and right-to-left cardiac shunt. Eight PFO patients without migraine but with large right-to-left shunt and 12 MA patients without PFO served as controls. Four MA patients with PFO were reexamined with sham injections of saline without microbubbles. Bioelectrical activity was evaluated using spectral electroencephalography and, passage of microbubbles through cerebral arteries was monitored with transcranial Doppler ultrasound. Microbubble embolism caused significant electroencephalographic power increase in MA+PFO patients but not in control groups including the sham-injected MA+PFO patients. Headache developed in 2 MA with PFO patients after microbubble injection. Conclusions These findings demonstrate that air microembolism through large PFOs may cause cerebral bioelectrical disturbances and, occasionally, headache in MA patients, which may reflect an increased reactivity of their brain to transient subclinical hypoxia–ischemia, and suggest that paradoxical embolism is not a common cause of migraine but may induce headache in the presence of a large PFO and facilitating conditions. PMID:23316313

  17. Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia.

    PubMed

    Choi, Hyun Young; Park, Joon Ha; Chen, Bai Hui; Shin, Bich Na; Lee, Yun Lyul; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Yan, Bing Chun; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Kim, Sung Koo

    2016-09-01

    Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin-eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment.

  18. Protective Effects of Ferulic Acid against Chronic Cerebral Hypoperfusion-Induced Swallowing Dysfunction in Rats

    PubMed Central

    Asano, Takashi; Matsuzaki, Hirokazu; Iwata, Naohiro; Xuan, Meiyan; Kamiuchi, Shinya; Hibino, Yasuhide; Sakamoto, Takeshi; Okazaki, Mari

    2017-01-01

    Ferulic acid (FA), a phenolic phytochemical, has been reported to exert antioxidative and neuroprotective effects. In this study, we investigated the protective effects of FA against the dysfunction of the swallowing reflex induced by ligation of bilateral common carotid arteries (2VO) in rats. In 2VO rats, topical administration of water or citric acid to the pharyngolaryngeal region evoked a diminished number of swallowing events with prolonged latency compared to sham-operated control rats. 2VO rats had an increased level of superoxide anion radical, and decreased dopamine and tyrosine hydroxylase enzyme levels in the striatum, suggesting that 2VO augmented cerebral oxidative stress and impaired the striatal dopaminergic system. Furthermore, substance P (SP) expression in the laryngopharyngeal mucosa, which is believed to be positively regulated by dopaminergic signaling in the basal ganglia, was decreased in 2VO rats. Oral treatment with FA (30 mg/kg) for 3 weeks (from one week before 2VO to two weeks after) improved the swallowing reflex and maintained levels of striatal dopamine and laryngopharyngeal SP expression in 2VO rats. These results suggest that FA maintains the swallowing reflex by protecting the dopamine-SP system against ischemia-induced oxidative damage in 2VO rats. PMID:28273833

  19. Cinnamaldehyde reduces IL-1beta-induced cyclooxygenase-2 activity in rat cerebral microvascular endothelial cells.

    PubMed

    Guo, Jian-You; Huo, Hai-Ru; Zhao, Bao-Sheng; Liu, Hong-Bin; Li, Lan-Fang; Ma, Yue-Ying; Guo, Shu-Ying; Jiang, Ting-Liang

    2006-05-10

    Cinnamaldehyde is a principle compound isolated from Guizhi-Tang, which is a famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions. The aim of the present study was to investigate the effects of cinnamaldehyde on expression and activity of cyclooxygenase (COX) and prostaglandin E(2) (PGE(2)) in rat cerebral microvascular endothelial cells (RCMEC). RCMEC were cultured, and identified by immunohistochemistry for von Willebrand factor in cytoplasm of the cells. Then cells were incubated in M199 medium containing interleukin (IL)-1beta in the presence or absence of cinnamaldehyde. After incubation, the medium was collected and the amount of PGE(2) was measured by enzyme-linked immunosorbent assay (ELISA). The cells were harvested, mRNA expression and activity of COX were analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR) with SYBR Green dye and ELISA respectively. Positive immunostaining for von Willebrand factor was present diffusely in the cytoplasm of >95% RCMEC. IL-1beta increased the mRNA expression and activity of COX-2, and production of PGE(2) in a dose- and time-dependent manner in RCMEC, while mRNA and activity of COX-1 were not significantly altered. Cinnamaldehyde significantly decreased IL-1beta-induced COX-2 activity and PGE(2) production in a dose-dependent manner, while it showed no inhibitory effect on IL-1beta-induced COX-2 mRNA expression in cultured RCMEC. In conclusion, cinnamaldehyde reduces IL-1beta-induced COX-2 activity, but not IL-1beta-induced COX-2 mRNA expression, and consequently inhibits production of PGE(2) in cultured RCMEC.

  20. Procaspase-9 induces its cleavage by transnitrosylating XIAP via the Thioredoxin system during cerebral ischemia-reperfusion in rats

    PubMed Central

    Zhang, Dengyue; Zhao, Ningjun; Ma, Bin; Wang, Yan; Zhang, Gongliang; Yan, Xianliang; Hu, Shuqun; Xu, Tie

    2016-01-01

    Transnitrosylation is an important mechanism by which nitric oxide (NO) modulates cell signaling pathways. For instance, SNO-caspase-3 can transnitrosylate the X-linked inhibitor of apoptosis (XIAP) to enhance apoptosis. XIAP is a potent antagonist of caspase apoptotic activity. Decrease in XIAP activity via nitrosylation results in SNO-XIAP-mediated caspase activation. Considering the functional liaison of procaspase-9 and XIAP, we hypothesized that procaspase-9 nitrosylates XIAP directly. Our data confirmed that cerebral ischemia-reperfusion induced XIAP nitrosylation, procaspase-9 denitrosylation and cleavage. Interestingly, the time courses of the nitrosylation of procaspase-9 and XIAP were negatively correlated, which was more prominent after cerebral ischemia-reperfusion, suggesting a direct interaction. The nitrosylation of XIAP, as well as the denitrosylation and cleavage of procaspase-9, were inhibited by DNCB, TrxR1 AS-ODNs, or TAT-AVPY treatment. Meanwhile, DNCB, TrxR1 AS-ODNs, or TAT-AVPY also inhibited the decrease in hippocampal CA1 neurons induced by ischemia-reperfusion in rats. The denitrosylation and cleavage of procaspase-9 induced by OGD/reoxygenation in SH-SY5Y cells were inhibited when cells were co-transfected with wild-type procaspase-9 and XIAP mutant (C449G). These data suggest that cerebral ischemia-reperfusion induces a transnitrosylation from procaspase-9 to XIAP via the Trx system to consequently cause apoptosis. Additionally, Cys325 is a critical S-nitrosylation site of procaspase-9. PMID:27052476

  1. Ginsenoside Rg1 prevents cerebral and cerebellar injury induced by obstructive jaundice in rats via inducing expression of TIPE-2.

    PubMed

    Zhou, Tingting; Zu, Guo; Zhou, Lu; Che, Ningwei; Guo, Jing; Liang, Zhanhua

    2016-01-01

    The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats.

  2. Effect of age on exercise-induced alterations in cognitive executive function: relationship to cerebral perfusion.

    PubMed

    Lucas, Samuel J E; Ainslie, Philip N; Murrell, Carissa J; Thomas, Kate N; Franz, Elizabeth A; Cotter, James D

    2012-08-01

    Regular exercise improves the age-related decline in cerebral blood flow (CBF) and is associated with improved cognitive function; however, less is known about the direct relationship between CBF and cognitive function. We examined the influence of healthy aging on the capability of acute exercise to improve cognition, and whether exercise-induced improvements in cognition are related to CBF and cortical hemodynamics. Middle cerebral artery blood flow velocity (MCAv; Doppler) and cortical hemodynamics (NIRS) were measured in 13 young (24±5 y) and 9 older (62±3 y) participants at rest and during cycling at 30% and 70% of heart rate range (HRR). Cognitive performance was assessed using a computer-adapted Stroop task (i.e., test of executive function cognition) at rest and during exercise. Average response times on the Stroop task were slower for the older compared to younger group for both simple and difficult tasks (P<0.01). Independent of age, difficult-task response times improved during exercise (P<0.01), with the improvement greater at 70% HRR exercise (P=0.04 vs. 30% HRR). Higher MCAv was correlated with faster response times for simple and difficult tasks at rest (R(2)=0.47 and R(2)=0.47, respectively), but this relation uncoupled progressively during exercise. Exercise-induced increases in MCAv were similar and unaltered during cognitive tasks for both age groups. In contrast, prefrontal cortical hemodynamic NIRS measures [oxyhemoglobin (O(2)Hb) and total hemoglobin (tHb)] were differentially affected by exercise intensity, age and cognitive task; e.g., there were smaller increases in [O(2)Hb] and [tHb] in the older group between exercise intensities (P<0.05). These data indicate that: 1) Regardless of age, cognitive (executive) function is improved while exercising; 2) while MCAv is strongly related to cognition at rest, this relation becomes uncoupled during exercise, and 3) there is dissociation between global CBF and regional cortical oxygenation and

  3. Neuroplastic Sensorimotor Resting State Network Reorganization in Children With Hemiplegic Cerebral Palsy Treated With Constraint-Induced Movement Therapy.

    PubMed

    Manning, Kathryn Y; Menon, Ravi S; Gorter, Jan Willem; Mesterman, Ronit; Campbell, Craig; Switzer, Lauren; Fehlings, Darcy

    2016-02-01

    Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy.

  4. [Changes in the activity of the ciliary apparatus of the cerebral aqueduct ependymal cells induced by some cerebrospinal fluid neurotransmitters].

    PubMed

    2010-01-01

    In vitro investigation of the effect of the neurotransmitter amino acids on motile activity of the ciliary apparatus of cerebral (Sylvian) aqueduct ependymal cells in the newborn rats has shown that the addition of glutamate, GABA, glycine, and taurine to the nutrient medium induced deceleration and, finally, complete disappearance of motile activity of the ciliary apparatus. Inhibition and blocking of the ciliary activity induced by the neurotransmitters, especially by high concentrations of glutamate, indicate the existence of respective receptors on the membrane of the cerebral aqueduct ependymal cells. This involvement of the receptors was confirmed in the experiments with the preliminary introduction of ion channel blockers (ketamine, strychnine, and bicuculine) into the culture medium that resulted in the attenuation of neurotransmitter destructive effect and the prolongation of motile activity of the ciliary apparatus.

  5. Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia.

    PubMed

    Tai, Kwok-Keung; Truong, Daniel D

    2007-09-20

    Although the mechanism underlying the anti-epileptic effects of a ketogenic diet (KD) is not known, KD is reported to be an effective treatment for intractable epilepsy, in particular among children. Here, we evaluated whether a KD can reduce posthypoxic seizure and myoclonic jerks in a rat model of cardiac arrest-induced cerebral hypoxia. In this study, rats were divided into two groups: one group received a normal diet while the other group was fed a KD for 25 days before being subjected to cardiac arrest-induced cerebral hypoxia. We found that rats fed a normal diet developed seizures and severe myoclonic jerks in response to auditory stimuli after the hypoxic insults, whereas the rats on the KD did not develop seizure and showed much less severe myoclonic jerks in response to auditory stimuli. The results suggested that the KD has beneficial effects against posthypoxic seizure and myoclonus.

  6. CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature

    PubMed Central

    Swanson, Phillip A.; Hart, Geoffrey T.; Russo, Matthew V.; Nayak, Debasis; Yazew, Takele; Peña, Mirna; Khan, Shahid M.; Pierce, Susan K.; McGavern, Dorian B.

    2016-01-01

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death. At the peak of ECM, we revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8+ T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells (pRBCs) from cerebral blood vessels, but were not required for the disease. Interestingly, the majority of disease-inducing parasite-specific CD8+ T cells interacted with the lumen of brain vascular endothelial cells (ECs), where they were observed surveying, dividing, and arresting in a cognate peptide-MHC I dependent manner. These activities were critically dependent on IFN-γ, which was responsible for activating cerebrovascular ECs to upregulate adhesion and antigen-presenting molecules. Importantly, parasite-specific CD8+ T cell interactions with cerebral vessels were impaired in chimeric mice rendered unable to present EC antigens on MHC I, and these mice were in turn resistant to fatal brainstem pathology. Moreover, anti-adhesion molecule (LFA-1 / VLA-4) therapy prevented fatal disease by rapidly displacing luminal CD8+ T cells from cerebrovascular ECs without affecting extravascular T cells. These in vivo data demonstrate that parasite-specific CD8+ T cell-induced fatal vascular breakdown and subsequent neuronal death during ECM is associated with luminal, antigen

  7. Ischemic postconditioning may not influence early brain injury induced by focal cerebral ischemia/reperfusion in rats

    PubMed Central

    Kim, Yoo Kyung; Shin, Jin Woo; Joung, Kyoung Woon

    2010-01-01

    Background Experimental studies have shown that ischemic postconditioning can reduce neuronal injury in the setting of cerebral ischemia, but the mechanisms are not yet clearly elucidated. This study was conducted to determine whether ischemic postconditioning can alter expression of heat shock protein 70 and reduce acute phase neuronal injury in rats subjected to transient focal cerebral ischemia/reperfusion. Methods Focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion for 60 min in twenty male Sprague-Dawley rats (250-300 g). Rats were randomized into control group and an ischemic postconditioning group (10 rats per group). The animals of control group had no intervention either before or after MCA occlusion. Ischemic postconditioning was elicited by 3 cycles of 30 s reperfusion interspersed by 10 s ischemia immediately after onset of reperfusion. The infarct ratios, brain edema ratios and motor behavior deficits were analyzed 24 hrs after ischemic insult. Caspase-3 reactive cells and cells showing heat shock protein 70 activity were counted in the caudoputamen and frontoparietal cortex. Results Ischemic postconditiong did not reduce infarct size and brain edema ratios compared to control group. Neurologic scores were not significantly different between groups. The number of caspase-3 reactive cells in the ischemic postconditioning group was not significantly different than the value of the control group in the caudoputamen and frontoparietal cortex. The number of cells showing heat shock protein 70 activity was not significantly different than the control group, as well. Conclusions These results suggest that ischemic postconditioning may not influence the early brain damage induced by focal cerebral ischemia in rats. PMID:20498797

  8. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice

    PubMed Central

    Choi, Ko-Eun; Hall, Casey L.; Sun, Jin-Mei; Wei, Ling; Mohamad, Osama; Dix, Thomas A.; Yu, Shan P.

    2012-01-01

    Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5–2.5 mg/kg, i.p.) reduces body and brain temperature by 2–5°C in 15–30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ∼30–40% when PIH therapy is initiated either immediately after stroke induction or after 30–60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries. Choi, K.-E., Hall, C. L., Sun, J.-M., Wei, L., Mohamad, O., Dix, T. A., Yu, S. P. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. PMID:22459147

  9. Detection of time window of cerebral blood flow response induced by sciatic nerve stimulation using temporal clustering analysis

    NASA Astrophysics Data System (ADS)

    Wang, Zheng; Luo, Qingming; Cheng, Haiying; Zeng, Shaoqun

    2003-07-01

    In many studies on functional neuroimaging, change in local cerebral blood flow (CBF) induced by sensory stimulation is used as a substitutive marker for change in cortical neuronal activity by Roy and Sherrington"s postulation. The purpose of this study is to evaluate the close temporal relationship between evoked local CBF and neuronal activity through utilizing temporal clustering analysis (TCA) method to analyze the dataset obtained by high-resolution laser speckle imaging (LSI). We mapped a relatively large somatosensory area of cerebral cortex in successively and followed variations of cerebral blood flow under sciatic nerve stimulation in anesthetized rats using LSI technique. Then we illustrated TCA method on the optical imaging signals and investigated the temporal characteristics of CBF activation. Contralateral somatosensory cortical microflow was activated to increase promptly in less than 1 second after the onset of 2 seconds electrical stimulation (pulse parameters: 0.5ms, 5Hz, 350mV). The data of the present study may possibly shed light on the development question of functional magnetic resonance imaging (fMRI) whether the ultimate spatial resolution attainable by fMRI is limited by the physiology of the cerebral blood flow response to activation or by the hardware and signal-to-noise ratio.

  10. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    PubMed

    Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  11. Long-Term Outcome of Transcatheter Subsegmental and Segmental Arterial Chemoemobolization Using Lipiodol for Hepatocellular Carcinoma

    SciTech Connect

    Takaki, Satoshi; Sakaguchi, Hiroshi; Anai, Hiroshi Tanaka, Toshihiro; Yamamoto, Kiyosei; Morimoto, Kengo; Nishiofuku, Hideyuki; Inoue, Masayoshi; Sueyoshi, Satoru; Nagata, Takeshi; Hidaka, Teruyuki; Uchida, Hideo; Kichikawa, Kimihiko

    2012-06-15

    Purpose: To clarify the efficacy of transcatheter hepatic sub-subsegmental, subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who had been treated using subseg/seg lip-TACE alone were retrospectively examined. Materials and Methods: Subjects comprised 199 patients with HCC (T1/2/{>=}3 = 30/108/61; Child-Pugh A/B/C = 115/52/32; Japan Integrated Staging [JIS] score {<=}1/2/{>=}3 = 88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed with an anticancer drug followed by injection of gelatin sponge particles. Each patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7-, and 10-year cumulative survival rates were calculated. Subgroup analyses were performed by stratifying the population according to T-factor, Child-Pugh classification, and JIS score. Results: Median duration of follow-up was 3.8 years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7- and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS {<=}1, respectively. Significant survival differences were found across two subgroups of staging systems (T2 vs. T3{<=} [P = 0.0012] and JIS score {<=}1 vs. 2 [P = 0.0036]). Conclusion: This study demonstrated that subseg/seg lip-TACE is a feasible treatment for obtaining prolonged survival in patients with localized HCC showing rich vasculature. Outcomes are influenced by both tumor stage and liver function, as seen in the best prolonged survival in patients with JIS score {<=}1.

  12. Extremely low frequency magnetic field induced changes in motor behaviour of gerbils submitted to global cerebral ischemia.

    PubMed

    Rauš, Snežana; Selaković, Vesna; Radenović, Lidija; Prolić, Zlatko; Janać, Branka

    2012-03-17

    The purpose of this study was to evaluate behavioural effects of an extremely low frequency magnetic field (ELF-MF) in 3-month-old Mongolian gerbils submitted to global cerebral ischemia. After 10-min occlusion of both common carotid arteries, the gerbils were placed in the vicinity of an electromagnet and continuously exposed to ELF-MF (50Hz, 0.5mT) for 7 days. Their behaviour (locomotion, stereotypy, rotations, and immobility) was monitored on days 1, 2, 4, 7, and 14 after reperfusion for 60min in the open field. It was shown that the 10-min global cerebral ischemia per se induced a significant motor activity increase (locomotion, stereotypy and rotations), and consequently immobility decrease until day 4 after reperfusion, compared to control gerbils. Exposure to ELF-MF inhibited development of ischemia-induced motor hyperactivity during the whole period of registration, but significantly in the first 2 days after reperfusion, when the postischemic hyperactivity was most evident. Motor activity of these gerbils was still significantly increased compared to control ones, but only on day 1 after reperfusion. Our results revealed that the applied ELF-MF (50Hz, 0.5mT) decreased motor hyperactivity induced by the 10-min global cerebral ischemia, via modulation of the processes that underlie this behavioural response.

  13. Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

    PubMed Central

    Ma, Jing; Bo, Shu-hong; Lu, Xiao-tong; Xu, A-jing; Zhang, Jian

    2016-01-01

    Carnosine is a dipeptide that scavenges free radicals, inhibits inflammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immunofluorescence staining were performed. Carnosine (200, 500 mg/kg) substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss. PMID:27857746

  14. Mirror visual feedback induces lower neuromuscular activity in children with spastic hemiparetic cerebral palsy.

    PubMed

    Feltham, Max G; Ledebt, Annick; Deconinck, Frederik J A; Savelsbergh, Geert J P

    2010-01-01

    The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The 'mirror box' creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two arms. The study incorporated two additional visual feedback conditions by placing a glass or opaque screen between the arms. During bilateral symmetric circular arm movements mirror visual feedback induced lower neuromuscular intensities in the shoulder muscles of the less impaired arm of children with SHCP compared to the other visual conditions. In addition, the mirror lead to shorter relative durations of eccentric and concentric activity in the elbow muscles of the more impaired arm, whereas no effects of visual feedback were found in a matched control group. These results suggest that replacing veridical visual information of the more impaired arm with a mirror reflection of the less impaired arm improves the motor control of children with SHCP during interlimb coupling. The effects of the availability of visual feedback in individuals with hemiparesis are discussed with reference to: (1) increase ipsilateral motor cortex excitability and (2) congruence between afferent (visual) feedback and the internal copy of the motor commands.

  15. Catalase prevents elevation of [Ca(2+)](i) induced by alcohol in cultured canine cerebral vascular smooth muscle cells: Possible relationship to alcohol-induced stroke and brain pathology.

    PubMed

    Li, Wenyan; Liu, Weimin; Altura, Bella T; Altura, Burton M

    2003-01-15

    Several studies have suggested that alcohol-induced brain injury is associated with generation of reactive oxygen species (ROS). The recent findings, that antioxidants (Vitamin E and pyrrolidine dithiocarbamate (PDTC)) prevent intracellular Ca(2+) ([Ca(2+)](i)) overload in cerebral vascular smooth muscle cells, induced by alcohol, demonstrate indirectly that ROS formation is related to cerebral vascular injury. The present experiments were designed to test the hypothesis that catalase, an hydrogen peroxide (H(2)O(2)) scavenging enzyme, can prevent or ameliorate alcohol-induced elevation of [Ca(2+)](i). Preincubation of cultured canine cerebral vascular smooth muscle cells with catalase (20-1000 units/ml) didn't produce any apparent changes from controls in resting levels of [Ca(2+)](i) after 1-3 days. Exposure of the cerebral vascular cells to culture media containing 10-100mM ethanol resulted in significant rises in [Ca(2+)](i) (p<0.01). Although exposure of these cells to a low concentration of catalase (20 units/ml) failed to prevent the increased level of [Ca(2+)](i) induced by ethanol, concomitant addition of higher concentrations of catalase (100-1000 units/ml) and ethanol (10-100mM) inhibited or ameliorated the rises of [Ca(2+)](i) induced by ethanol either at 24h or at 3 days, in a concentration-dependent manner. Catalase, in the range of 100-200 units/ml, inhibited approximately 50% of the [Ca(2+)](i) increases caused by ethanol in the first 24h. Catalase at a concentration of 1000 units/ml inhibited completely excessive [Ca(2+)](i) accumulation. The present results when viewed in light of other recently published data suggest that H(2)O(2) generation may be one of the earliest events triggered by alcohol in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

  16. Sources of activator calcium for potassium- and serotonin-induced constriction of isolated bovine cerebral arteries

    SciTech Connect

    Not Available

    1986-03-01

    Previous in vitro studies with the calcium channel blockers (CCB) indirectly suggest that K/sup +/ and serotonin (5HT) constrict bovine middle cerebral arteries (BMCA) by promoting the influx of extracellular calcium (Ca) through CCB-sensitive channels. In this study, the authors directly determined the sources of activator Ca for K/sup +/- and 5HT-induced constriction of BMCA, using radiolabelled /sup 4/)2%Ca and /sup 3/H-sorbitol. EGTA-resistant Ca uptake, an estimate of Ca influx into vascular smooth muscle, was determined by exposure to Ca-deficient 2 mM EGTA solutions at 1/sup 0/C. The total Ca content of BMCA was 4.4 nmole/mg (wet wt.) after equilibration at 37/sup 0/C. The total exchangeable Ca content was 1.64 nmole/mg after 1 hr of /sup 45/Ca loading; the Ca content of the extracellular water was 0.30 nmole/mg, as estimated from the /sup 3/H-sorbitol space (0.25 ul/mg). The EGTA-resistant Ca uptake at 1 hr was 134 pmole/mg. K/sup +/ and 5HT significantly increased EGTA-resistant Ca uptake during 5 min of /sup 45/Ca loading; for K/sup +/, Ca uptake increased from 71 to 202 pmole/mg, and for 5HT, from 65 to 102 pmole/mg. Verapamil (10/sup -5/ M) or nifedipine (3.3 x 10/sup -7/ M) significantly blocked the increase in EGTA-resistant Ca uptake induced by K/sup +/ or 5HT. These results provide direct evidence that K/sup +/ or 5HT may constrict BMCA by promoting the influx of extracellular Ca through CCB-sensitive channels.

  17. Cerebral white matter oxidation and nitrosylation in young rodents with kaolin-induced hydrocephalus.

    PubMed

    Del Bigio, Marc R; Khan, Osaama H; da Silva Lopes, Luiza; Juliet, Packiasamy A R

    2012-04-01

    Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1α was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.

  18. Brown propolis attenuates cerebral ischemia-induced oxidative damage via affecting antioxidant enzyme system in mice.

    PubMed

    Bazmandegan, Gholamreza; Boroushaki, Mohammad Taher; Shamsizadeh, Ali; Ayoobi, Fatemeh; Hakimizadeh, Elham; Allahtavakoli, Mohammad

    2017-01-01

    Oxidative stress plays a critical role in ischemic brain injury. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are the enzymes underlying the endogenous antioxidant mechanisms affected by stroke and are considered as oxidative stress biomarkers. Brown propolis (BP) is a bioactive natural product with a set of biological activities that in turn may differ depending on the area from which the substance is originated. The aim of this study was to investigate the effect of water-extracted brown propolis (WEBPs), from two regions of Iran, against cerebral ischemia-induced oxidative injury in a mouse model of stroke. Experimentally, the chemical characterization and total polyphenol content were determined using GC/MS and Folin-Ciocalteu assay respectively. Seventy-two adult male mice were randomly divided into the surgical sham group, control group (treated with vehicle), and four groups of WEBPs-treated animals. The WEBPs were administered at the doses of 100 and 200mg/kg IP, during four different time points. Oxidative stress biomarkers (SOD and GPx activity, SOD/GPx ratio), lipid peroxidation (LPO) index (malondialdehyde content) and infarct volume were measured 48h post stroke. Behavioral tests were evaluated 24 and 48h after stroke. WEBPs treatment resulted in significant restoration of antioxidant enzymes activity and a subsequent decrease in LPO as well as the infarct volume compared to the control group. Sensory-motor impairment and neurological deficits were improved significantly as well. These results indicate that Iranian BP confers neuroprotection on the stroke-induced neuronal damage via an antioxidant mechanism which seems to be mediated by the endogenous antioxidant system.

  19. Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway.

    PubMed

    Guo, Chao; Wang, Shiquan; Duan, Jialin; Jia, Na; Zhu, Yanrong; Ding, Yi; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

    2017-03-01

    Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. The experiment stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). To model ischemia-like conditions in vitro, differentiated SH-SY5Y cells were exposed to transient oxygen and glucose deprivation (OGD). Treatment with PCA significantly improved neurologic score, reduced infarct volume and necrotic neurons, and also decreased reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents at 24 h after reperfusion. Meanwhile, PCA significantly increased the transcription nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in the ischemic cerebral cortex as shown by immunofluorescence staining and Western blot analysis. In vitro experiment showed that PCA protected differentiated SH-SY5Y cells against OGD-induced injury. Likewise, PCA also increased markedly the Nrf2 and HO-1 expressions in a dose-dependent manner. The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.

  20. [Improvement of the viscosity and the intrahepatic distribution of miriplatin-lipiodol suspension].

    PubMed

    Kishimoto, Shuichi; Adachi, Shingo; Masui, Aya; Suzuki, Ryosuke; Fukushima, Shoji

    2014-11-01

    The effects of warming or emulsification with the water-soluble contrast medium, Iomeron (IOM), on reducing the viscosity of miriplatin-lipiodol (MPT-LPD) suspension were studied. Reduction in the viscosity of MPT-LPD suspension was ob- served upon increasing the temperature. Although the O/W MPT-LPD emulsion with a low ratio of MPT-LPD to IOM reduced the viscosity, the effect was lesser than that achieved with the warming treatment. Radiographic images of the liver obtained after administration of the emulsion into the rat portal vein showed that warming resulted in improved intrahepatic distribution of the formulation, which was dependent on the reduction of viscosity. Emulsification also led to better intrahepatic distribution, but this distribution did not depend on the viscosity of the formulation. The MPT-LPD emulsion showed different distribution properties from the MPT-LPD suspension, and it was difficult to estimate the intrahepatic distribution property from the viscosity of the emulsion. Thus, we suggest that emulsification and warming of MPT-LPD are effective methods for improving the intrahepatic distribution of the MPT formulation.

  1. Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia/Reperfusion-Induced Damage to CA1 Hippocampal Neurons

    PubMed Central

    Hao, Lingyun; Wei, Xuewen; Guo, Peng; Zhang, Guangyi; Qi, Suhua

    2016-01-01

    Nitric oxide (NO) can regulate signaling pathways via S-nitrosylation. Fyn can be post-translationally modified in many biological processes. In the present study, using a rat four-vessel-occlusion ischemic model, we aimed to assess whether Fyn could be S-nitrosylated and to evaluate the effects of Fyn S-nitrosylation on brain damage. In vitro, Fyn could be S-nitrosylated by S-nitrosoglutathione (GSNO, an exogenous NO donor), and in vivo, endogenous NO synthesized by NO synthases (NOS) could enhance Fyn S-nitrosylation. Application of GSNO, 7-nitroindazole (7-NI, an inhibitor of neuronal NOS) and hydrogen maleate (MK-801, the N-methyl-d-aspartate receptor (NMDAR) antagonist) could decrease the S-nitrosylation and phosphorylation of Fyn induced by cerebral ischemia/reperfusion (I/R). Cresyl violet staining validated that these compounds exerted neuroprotective effects against the cerebral I/R-induced damage to hippocampal CA1 neurons. Taken together, in this study, we demonstrated that Fyn can be S-nitrosylated both in vitro and in vivo and that inhibiting S-nitrosylation can exert neuroprotective effects against cerebral I/R injury, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stroke and the development of novel treatment strategies. PMID:27420046

  2. Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia/Reperfusion-Induced Damage to CA1 Hippocampal Neurons.

    PubMed

    Hao, Lingyun; Wei, Xuewen; Guo, Peng; Zhang, Guangyi; Qi, Suhua

    2016-07-12

    Nitric oxide (NO) can regulate signaling pathways via S-nitrosylation. Fyn can be post-translationally modified in many biological processes. In the present study, using a rat four-vessel-occlusion ischemic model, we aimed to assess whether Fyn could be S-nitrosylated and to evaluate the effects of Fyn S-nitrosylation on brain damage. In vitro, Fyn could be S-nitrosylated by S-nitrosoglutathione (GSNO, an exogenous NO donor), and in vivo, endogenous NO synthesized by NO synthases (NOS) could enhance Fyn S-nitrosylation. Application of GSNO, 7-nitroindazole (7-NI, an inhibitor of neuronal NOS) and hydrogen maleate (MK-801, the N-methyl-d-aspartate receptor (NMDAR) antagonist) could decrease the S-nitrosylation and phosphorylation of Fyn induced by cerebral ischemia/reperfusion (I/R). Cresyl violet staining validated that these compounds exerted neuroprotective effects against the cerebral I/R-induced damage to hippocampal CA1 neurons. Taken together, in this study, we demonstrated that Fyn can be S-nitrosylated both in vitro and in vivo and that inhibiting S-nitrosylation can exert neuroprotective effects against cerebral I/R injury, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stroke and the development of novel treatment strategies.

  3. Multimodal Neuroprotection Induced by PACAP38 in Oxygen–Glucose Deprivation and Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Cohen, Gadi; Arien-Zakay, Hadar; Chen, Jieli; Zhang, Chunling; Chopp, Michael; Jiang, Hao

    2014-01-01

    Pituitary adenylate cyclase activating peptide (PACAP), a potent neuropeptide which crosses the blood–brain barrier, is known to provide neuroprotection in rat stroke models of middle cerebral artery occlusion (MCAO) by mechanism(s) which deserve clarification. We confirmed that following i.v. injection of 30 ng/kg of PACAP38 in rats exposed to 2 h of MCAO focal cerebral ischemia and 48 h reoxygenation, 50 % neuroprotection was measured by reduced caspase-3 activity and volume of cerebral infarction. Similar neuroprotective effects were measured upon PACAP38 treatment of oxygen–glucose deprivation and reoxygenation of brain cortical neurons. The neuroprotection was temporally associated with increased expression of brain-derived neurotrophic factor, phosphorylation of its receptor—tropomyosin-related kinase receptor type B (trkB), activation of phosphoinositide 3-kinase and Akt, and reduction of extracellular signal-regulated kinases 1/2 phosphorylation. PACAP38 increased expression of neuronal markers beta-tubulin III, microtubule-associated protein-2, and growth-associated protein-43. PACAP38 induced stimulation of Rac and suppression of Rho GTPase activities. PACAP38 down-regulated the nerve growth factor receptor (p75NTR) and associated Nogo-(Neurite outgrowth-A) receptor. Collectively, these in vitro and in vivo results propose that PACAP exhibits neuroprotective effects in cerebral ischemia by three mechanisms: a direct one, mediated by PACAP receptors, and two indirect, induced by neurotrophin release, activation of the trkB receptors and attenuation of neuronal growth inhibitory signaling molecules p75NTR and Nogo receptor. PMID:22678884

  4. Multimodal neuroprotection induced by PACAP38 in oxygen-glucose deprivation and middle cerebral artery occlusion stroke models.

    PubMed

    Lazarovici, Philip; Cohen, Gadi; Arien-Zakay, Hadar; Chen, Jieli; Zhang, Chunling; Chopp, Michael; Jiang, Hao

    2012-11-01

    Pituitary adenylate cyclase activating peptide (PACAP), a potent neuropeptide which crosses the blood-brain barrier, is known to provide neuroprotection in rat stroke models of middle cerebral artery occlusion (MCAO) by mechanism(s) which deserve clarification. We confirmed that following i.v. injection of 30 ng/kg of PACAP38 in rats exposed to 2 h of MCAO focal cerebral ischemia and 48 h reoxygenation, 50 % neuroprotection was measured by reduced caspase-3 activity and volume of cerebral infarction. Similar neuroprotective effects were measured upon PACAP38 treatment of oxygen-glucose deprivation and reoxygenation of brain cortical neurons. The neuroprotection was temporally associated with increased expression of brain-derived neurotrophic factor, phosphorylation of its receptor-tropomyosin-related kinase receptor type B (trkB), activation of phosphoinositide 3-kinase and Akt, and reduction of extracellular signal-regulated kinases 1/2 phosphorylation. PACAP38 increased expression of neuronal markers beta-tubulin III, microtubule-associated protein-2, and growth-associated protein-43. PACAP38 induced stimulation of Rac and suppression of Rho GTPase activities. PACAP38 downregulated the nerve growth factor receptor (p75(NTR)) and associated Nogo-(Neurite outgrowth-A) receptor. Collectively, these in vitro and in vivo results propose that PACAP exhibits neuroprotective effects in cerebral ischemia by three mechanisms: a direct one, mediated by PACAP receptors, and two indirect, induced by neurotrophin release, activation of the trkB receptors and attenuation of neuronal growth inhibitory signaling molecules p75(NTR) and Nogo receptor.

  5. Neuroprotective effects of gallic acid against hypoxia/reoxygenation-induced mitochondrial dysfunctions in vitro and cerebral ischemia/reperfusion injury in vivo.

    PubMed

    Sun, Jing; Li, Yun-Zi; Ding, Yin-Hui; Wang, Jin; Geng, Ji; Yang, Huan; Ren, Jie; Tang, Jin-Yan; Gao, Jing

    2014-11-17

    Oxidative stress and mitochondrial dysfunction are frequently implicated in the pathology of secondary neuronal damage following cerebral ischemia/reperfusion. Recent evidence suggests that gallic acid (GA) reverses oxidative stress in rat model of streptozotocin-induced dementia, but the roles and mechanisms of GA on cerebral ischemia/reperfusion injury remain unknown. Here we investigated the potential roles and mechanisms of GA in hypoxia/reoxygenation induced by sodium hydrosulfite (Na2S2O4) in vitro and cerebral ischemia/reperfusion induced by middle cerebral artery occlusion (MCAO) in vivo. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazol carbocyanine iodide (JC-1), Dichlorofluorescin diacetate (DCF-DA) and MitoSOX fluorescent assay, Clark-type oxygen electrode, firefly luciferase assay, and calcium-induced mitochondrial swelling were conducted to detect cell death, mitochondrial membrane potential (MMP), intracellular and mitochondrial reactive oxygen species (ROS), oxygen consumption, ATP level, and mitochondrial permeability transition pore (MPTP) viability. We firstly find that modulation of the mitochondrial dysfunction is an important mechanism by GA attenuating hypoxia/reoxygenation insult. To further assess the effects of GA on cerebral ischemia/reperfusion injury, 2, 3, 5-triphenyl-tetrazolium chloride (TTC) staining, dUTP nick-end labeling (TUNEL) assay, and Cytochrome C (Cyt C) release were performed in MCAO rats. The results support that GA is useful against cerebral ischemia/reperfusion injury as a potential protective agent.

  6. Toll Like Receptor 4 Affects the Cerebral Biochemical Changes Induced by MPTP Treatment.

    PubMed

    Conte, Carmela; Roscini, Luca; Sardella, Roccaldo; Mariucci, Giuseppina; Scorzoni, Stefania; Beccari, Tommaso; Corte, Laura

    2017-02-01

    The etiology and pathogenesis of Parkinson's disease (PD) are still unclear. However, multiple lines of evidence suggest a critical role of the toll like receptor 4 (TLR4) in inflammatory response and neuronal death. Neuroinflammation may be associated with the misfolding and aggregation of proteins accompanied by a change in their secondary structure. Recent findings also suggest that biochemical perturbations in cerebral lipid content could contribute to the pathogenesis of central nervous system (CNS) disorders, including PD. Thus, it is of great importance to determine the biochemical changes that occur in PD. In this respect, Fourier Transform Infrared (FTIR) spectroscopy represents a useful tool to detect molecular alterations in biological systems in response to stress stimuli. By relying upon FTIR approach, this study was designed to elucidate the potential role of TLR4 in biochemical changes induced by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin in a mouse model of PD. The analysis of the FTIR spectra was performed in different brain regions of both wild type (WT) and toll like receptor 4-deficient (TLR4(-/-)) mice. It revealed that each brain region exhibited a characteristic molecular fingerprint at baseline, with no significant differences between genotypes. Conversely, WT and TLR4(-/-) mice showed differential biochemical response to MPTP toxicity, principally related to lipid and protein composition. These differences appeared to be characteristic for each brain area. Furthermore, the present study showed that WT mice resulted more vulnerable than TLR4(-/-) animals to striatal dopamine (DA) depletion following MPTP treatment. These results support the hypothesis of a possible involvement of TLR4 in biochemical changes occurring in neurodegeneration.

  7. Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile.

    PubMed

    Anand, R; Shankar, J; Tiwary, B N; Singh, A P

    2015-04-01

    Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.

  8. Chronic lead treatment accelerates photochemically induced platelet aggregation in cerebral microvessels of mice, in vivo

    SciTech Connect

    Al Dhaheri, A.H.; El-Sabban, F.; Fahim, M.A.

    1995-04-01

    Effects of two chronic treatment levels with lead on platelet aggregation in cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead was made by subcutaneous injections for 7 days of lead acetate dissolved in 5% glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10 each; one group was injected with vehicle (control), another was injected with the low dose, and the third was injected with the high dose. Additional mice were used for the determination of hematological parameters and for the lead level in serum of the three groups. On the eighth day, platelet aggregation in pial microvessels of these groups of mice was carried out in vivo. Animals were anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a craniotomy was performed. Platelet aggregation in pial microvessels was induced photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g, iv) with an intense mercury light. The time required for the first platelet aggregate to appear in pial arterioles was significantly shorter in the lead-treated mice than in control. This effect was in a dose-dependent manner; 113 {+-} 44 sec for low dose and 71 {+-} 18 sec for high dose vs 155 {+-} 25 sec for control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated groups, the high dose significantly (P < 0.05) shortened the time to first aggregate. These data evidenced an increased susceptibility to cerebrovascular thrombosis as a result of exposure to lead. 26 refs., 4 figs., 2 tabs.

  9. Transarterial Chemoembolization With Cisplatin as Second-Line Treatment for Hepatocellular Carcinoma Unresponsive to Chemoembolization With Epirubicin-Lipiodol Emulsion

    SciTech Connect

    Maeda, Noboru Osuga, Keigo; Higashihara, Hiroki; Tomoda, Kaname; Mikami, Koji; Nakazawa, Tetsuro; Nakamura, Hironobu; Tomiyama, Noriyuki

    2012-02-15

    Purpose: The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin-Lipiodol emulsion at our institution. Materials and Methods: Between January 2006 and March 2009, 51 patients with unresectable HCC underwent TACE using cisplatin. All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE using epirubicin-Lipiodol emulsion. TACE procedures consisted of arterial injection of a mixture of Lipiodol and cisplatin (30-100 mg [mean 57 {+-} 21]) (n = 29) or arterial infusion of cisplatin (30-100 mg [mean 87 {+-} 19]) solution (n = 22) followed by injection of 1-mm porous gelatin particles. Early tumor response was assessed by contrast-enhanced computed tomography (CT) according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver (EASL) criteria. Overall survival and progression-free survival was calculated using the Kaplan-Meier method. Toxicity was assessed according to NCI-CTCAE version 3 criteria. Results: Response rates were 11.8 and 27.5% by RECIST and EASL criteria, respectively. Overall survival rates were 61.9, 48.2, and 28.9% at 1, 2, and 3 years, respectively, and the median survival time was 15.4 months. Progression-free survival rate was 35.2% at 1 year, and median progression-free survival time was 3.1 months. No major complications were observed, and the occurrence of postembolization syndrome was minimal. Grade 3 to 4 toxicities included thrombocytopenia (5.8%), increased aspartate aminotransferase (AST) level (35.3%), and increased alanine aminotransferase (ALT) level (23.5%). Conclusions: witching the TACE anticancer drug from epirubicin to cisplatin might be the feasible option for advanced HCC, even when considered resistant to the initial form of TACE.

  10. Importance of extracellular Ca2+ and intracellular Ca2+ release in ethanol-induced contraction of cerebral arterial smooth muscle.

    PubMed

    Yang, Z; Wang, J; Zheng, T; Altura, B T; Altura, B M

    2001-07-01

    The present study was designed to investigate the roles of extracellular Ca2+ ([Ca2+]0) influx and intracellular free Ca2+ ([Ca2+]i) release in ethanol-induced contractions of isolated canine cerebral arteries and primary cultured, cerebral vascular smooth muscle cells. Ethanol (20-200 mM) produced significant contractions in isolated canine basilar arterial rings in a concentration-dependent manner. Removal of [Ca2+]0 and pretreatment of canine basilar arterial rings with verapamil (an antagonist of voltage-gated Ca2+ channels), thapsigargin (a selective antagonist of the sarcoplasmic reticulum Ca2+ pump), caffeine plus ryanodine (a specific antagonist of ryanodine-sensitive Ca2+ release), or heparin (an inositol 1,4,5,-trisphosphate [InsP3]-mediated Ca2+ release antagonist) markedly attenuated (approximately 50%-80%) ethanol-induced contractions. The absence of [Ca2+]0 and preincubation of primary single smooth muscle cells obtained from canine basilar arteries with verapamil, thapsigargin, heparin, or caffeine plus ryanodine markedly attenuated (approximately 50%-80%) the transient and sustained elevations in [Ca2+]i induced by ethanol. Results of the present study suggest to us that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores (both InsP3 sensitive and ryanodine sensitive) are required for ethanol-induced contractions of isolated canine basilar arteries.

  11. Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle.

    PubMed

    Yang, Z W; Wang, J; Zheng, T; Altura, B T; Altura, B M

    2001-05-01

    We investigated the relationships of two potential intracellular signaling pathways, protein kinase C (PKC) and phosphatidylinositol 3-kinases (PI3Ks), to ethanol-induced contractions in cerebral arteries. Ethanol (20-200 mM) induces concentration-dependent constriction in isolated canine basilar arteries that is inhibited in a concentration-dependent manner by pretreatment of these vessels with 10(-9)-10(-3) M Gö-6976 (an antagonist selective for PKC-alpha and PKC-betaI), 10(-10)-10(-4) M bisindolylmaleimide I (a specific antagonist of PKC), and 10(-10)-10(-4) M wortmannin or 10(-8)-10(-2) M LY-294002 (selective antagonists of PI3Ks). Ethanol-induced increases in intracellular Ca(2+) concentration (from approximately 100 to approximately 500 nM) in canine basilar smooth muscle cells are also suppressed markedly (approximately 20-70%) in the presence of a similar concentration range of Gö-6976, bisindolymaleimide I, wortmannin, or LY-294002. This study suggests that activation of PKC isoforms and PI3Ks appears to be an important signaling pathway in ethanol-induced vasoconstriction of cerebral blood vessels.

  12. Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus.

    PubMed

    Wang, Qun; Tompkins, Kenneth D; Simonyi, Agnes; Korthuis, Ronald J; Sun, Albert Y; Sun, Grace Y

    2006-05-23

    Increased production of reactive oxygen species (ROS) following cerebral ischemia-reperfusion (I/R) is an important underlying cause for neuronal injury leading to delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase inhibitor can protect against ischemia-induced ROS generation and decrease DND. Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30 min prior to ischemia significantly attenuated the early increase in HNE in hippocampus measured at 3 h after I/R. Apocynin also protected against I/R-induced neuronal degeneration and DND, oxidative DNA damage, and glial cell activation. Taken together, the neuroprotective effects of apocynin against ROS production during early phase of I/R and subsequent I/R-induced neuronal damage provide strong evidence that inhibition of NADPH oxidase could be a promising therapeutic mechanism to protect against stroke damage in the brain.

  13. Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema

    PubMed Central

    Chen, Shao-Jun; Yang, Jia-Fang; Kong, Fan-Ping; Ren, Ji-Long; Hao, Ke; Li, Min; Yuan, Yuan; Chen, Xin-Can; Yu, Ri-Sheng; Li, Jun-Fa; Leng, Gareth; Chen, Xue-Qun; Du, Ji-Zeng

    2014-01-01

    Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca2+, and PKCε; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1+ and AQP4+, we show that transfected CRFR1+ contributes to edema via transfected AQP4+. In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema. PMID:25146699

  14. Electroacupuncture-induced neuroprotection against focal cerebral ischemia in the rat is mediated by adenosine A1 receptors

    PubMed Central

    Dai, Qin-xue; Geng, Wu-jun; Zhuang, Xiu-xiu; Wang, Hong-fa; Mo, Yun-chang; Xin, He; Chen, Jiang-fan; Wang, Jun-lu

    2017-01-01

    The activation of adenosine A1 receptors is important for protecting against ischemic brain injury and pretreatment with electroacupuncture has been shown to mitigate ischemic brain insult. The aim of this study was to test whether the adenosine A1 receptor mediates electroacupuncture pretreatment-induced neuroprotection against ischemic brain injury. We first performed 30 minutes of electroacupuncture pretreatment at the Baihui acupoint (GV20), delivered with a current of 1 mA, a frequency of 2/15 Hz, and a depth of 1 mm. High-performance liquid chromatography found that adenosine triphosphate and adenosine levels peaked in the cerebral cortex at 15 minutes and 120 minutes after electroacupuncture pretreatment, respectively. We further examined the effect of 15 or 120 minutes electroacupuncture treatment on ischemic brain injury in a rat middle cerebral artery-occlusion model. We found that at 24 hours reperfusion,120 minutes after electroacupuncture pretreatment, but not for 15 minutes, significantly reduced behavioral deficits and infarct volumes. Last, we demonstrated that the protective effect gained by 120 minutes after electroacupuncture treatment before ischemic injury was abolished by pretreatment with the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 mg/kg, intraperitoneally). Our results suggest that pretreatment with electroacupuncture at the Baihui acupoint elicits protection against transient cerebral ischemia via action at adenosine A1 receptors.

  15. Intra-carotid cold magnesium sulfate infusion induces selective cerebral hypothermia and neuroprotection in rats with transient middle cerebral artery occlusion.

    PubMed

    Song, Wei; Wu, Yong-Ming; Ji, Zhong; Ji, Ya-Bin; Wang, Sheng-Nan; Pan, Su-Yue

    2013-04-01

    Local hypothermia induced by intra-arterial infusion of cold saline reduces brain injury in ischemic stroke. Administration of magnesium sulfate through the internal carotid artery is also known to reduce ischemic brain damage. The neuroprotective effects of combination therapy with local endovascular hypothermia and intra-carotid magnesium sulfate infusion has not been evaluated. The aim of the study was to determine whether infusion of intra-carotid cold magnesium offers neuroprotective efficacy superior to cold saline infusion alone. Sixty-eight Sprague-Dawley rats were subjected to 3 h of middle cerebral artery occlusion and were randomly divided into six groups: sham-operated group; stroke control group; local cold magnesium infusion group; local cold saline infusion group; local normothermic magnesium infusion group; and local normothermic saline infusion group. Before reperfusion, ischemic rats received local infusion or no treatment. Infarct volume, neurological deficit, and brain water content were evaluated at 48 h after reperfusion. Selective brain hypothermia (33-34 °C) was successfully induced by intra-carotid cold infusion. Local cold saline infusion and local cold magnesium infusion reduced the infarct volumes by 48 % (p < 0.001) and 65 % (p < 0.001), respectively, compared with stroke controls. Brain water content was decreased significantly in animals treated with local cold magnesium infusion. Furthermore, the rats given a local cold magnesium infusion had the best neurological outcome. Local normothermic infusion failed to improve ischemic brain damage. These data suggest that local hypothermia induced by intra-carotid administration of cold magnesium is more effective in reducing acute ischemic damage than infusion of cold saline alone.

  16. Effect of lipiodol and methylene blue on the thoracoscopic preoperative positioning.

    PubMed

    Zhang, Chuan-Yu; Yu, Hua-Long; Liu, Shi-He; Jiang, Gang; Wang, Yong-Jie

    2015-01-01

    The aim of this study was to compare and analyze the site-specific accuracy of mixture of lipiodol and methylene blue (MLM) (0.6 ml, 1:5) and pure methylene blue (0.5 ml) on the rabbit lungs. In this study, CT-guided percutaneous injection of MLM and methylene blue. Compare the staining degree by biopsy of lung tissue. Use 4 points system to evaluate the site-specific accuracy at 6h and 24 h after injection. For MLM, evaluate its radiopacity by radiation. When evaluate the positioning, 2 points mean acceptable, 3 points mean excellent. The results indicated that the staining range of MLM is obvious less than that of methylene blue (0.6 vs. 1.0 cm, P<0.01), but the staining capacity of MLM is higher than that of methylene blue (2.8 vs. 2.2, P = 0.01). About the staining abilities which are evaluated as excellent, MLM group accounts for 81%, methylene blue group accounts for 38% (P = 0.011). About the radiopacity which are evaluated as acceptable or excellent, MLM group accounts for 62%. With good direct vision, the suitable positioning rate of MLM can be 100%, which is better than that of methylene blue. In conclusion, percutaneous injection of MLM can be used to lung positioning. The result shows that use MLM is better than only using methylene blue. But it is necessary to do the investigation in human beings in order to confirm the feasibility of its clinical application.

  17. Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

    SciTech Connect

    Kawaoka, Tomokazu; Aikata, Hiroshi Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

    2009-07-15

    We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

  18. [Digital angiography and lipiodol computerized tomography in the anatomopathological framework of hepatocarcinoma].

    PubMed

    Pozzi-Mucelli, R; Pozzi-Mucelli, R; Pagnan, L; Dalla Palma, L

    1994-12-01

    The introduction of therapies other than conventional surgery of hepatocellular carcinoma (HCC) requires an accurate pathologic classification, which is important because it is well known that HCC may have multicentric growth. The Liver Cancer Study Group of Japan has proposed a classification dividing HCCs into three macroscopic forms from the pathologic point of view: nodular, massive and infiltrating HCCs. The nodular type is subdivided into four types: single nodular type, single nodular type with surrounding proliferation, multinodular fused type and multinodular type. Forty-six HCC patients were examined with Lipiodol Computed Tomography (LCT) to investigate the agreement between pathologic and imaging findings. LCT proved to be in close agreement with pathologic findings. Sixteen cases were classified as type I (single nodular type), 8 as type II (single nodular type with limited foci), 1 as type III (multinodular fused type), 18 as type IV (multiple nodular type with diffuse foci) and 3 cases as type V (massive form). No cases of infiltrative forms were observed in our series. Based on LCT findings, the capabilities of digital subtraction angiography (DSA) were studied in the pathologic classification of HCCs. DSA exhibited some limitations in the pathologic classification of HCCs in 5 of 16 patients with type I lesions. In these cases DSA suggested false-positive diagnoses because of regenerative nodules in cirrhotic liver in 3 cases and of daughter nodules (not confirmed at LCT) in 2 cases. In 7 of 8 patients with type II HCCs, DSA failed to show the daughter nodules surrounding the main nodule. In the 18 patients with multiple distant nodules (type IV), DSA was less sensitive in defining nodule number and site. In the massive form, the information obtained with LCT and DSA was comparable. In conclusion, LCT should be considered a basic examination in the study of HCC extent. Based on LCT findings, the most appropriate treatment can be selected, be it

  19. Neuroprotective effects of the P2 receptor antagonist PPADS on focal cerebral ischaemia-induced injury in rats.

    PubMed

    Lämmer, A; Günther, A; Beck, A; Krügel, U; Kittner, H; Schneider, D; Illes, P; Franke, H

    2006-05-01

    After acute injury of the central nervous system extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations as a result of cell damage and subsequent increase in membrane permeability. Released ATP may act as a toxic agent, which causes cellular degeneration and death, mediated through P2X and P2Y receptors. Mechanisms underlying the various effects of purinoceptor modulators in models of cerebral damage are still uncertain. In the present study the effect of P2 receptor inhibition after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats was investigated. Rats received either the non-selective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) or artificial cerebrospinal fluid (ACSF) as control by the intracerebroventricular route. First, these treatments were administered 10 min before MCAO and subsequently twice daily for 1 or 7 days after MCAO. The functional recovery of motor and cognitive deficits was tested at an elevated T-labyrinth. The PPADS-treated group showed a significant reduction of paresis-induced sideslips compared with ACSF-treated animals. Infarct volume was reduced in the PPADS group in comparison with the ACSF group. A significant decrease in intermediately and profoundly injured cells in favour of intact cells in the PPADS group was revealed by quantification of celestine blue/acid fuchsin-stained cells in the peri-infarct area. The data provide further evidence for the involvement of P2 receptors in the pathophysiology of cerebral ischaemia in vivo. The inhibition of P2 receptors at least partially reduces functional and morphological deficits after an acute cerebral ischaemic event.

  20. Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

    PubMed

    Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

    2015-12-01

    Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss.

  1. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

    NASA Astrophysics Data System (ADS)

    Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-04-01

    The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

  2. Modified Constraint-Induced Therapy for Children with Hemiplegic Cerebral Palsy: A Randomized Trial

    ERIC Educational Resources Information Center

    Wallen, Margaret; Ziviani, Jenny; Naylor, Olivia; Evans, Ruth; Novak, Iona; Herbert, Robert D.

    2011-01-01

    Aim: Conventional constraint-based therapies are intensive and demanding to implement, particularly for children. Modified forms of constraint-based therapies that are family-centred may be more acceptable and feasible for families of children with cerebral palsy (CP)-but require rigorous evaluation using randomized trials. The aim of this study…

  3. Neprilysin protects against cerebral amyloid angiopathy and Aβ-induced degeneration of cerebrovascular smooth muscle cells.

    PubMed

    Miners, James Scott; Kehoe, Patrick; Love, Seth

    2011-09-01

    Neprilysin (NEP), which degrades amyloid-β (Aβ), is expressed by neurons and cerebrovascular smooth muscle cells (CVSMCs). NEP immunolabeling is reduced within cerebral blood vessels of Alzheimer's disease (AD) patients with cerebral amyloid angiopathy (CAA). We have now measured NEP enzyme activity in leptomeningeal and purified cerebral cortical blood vessel preparations from control and AD patients with and without CAA. Measurements were adjusted for smooth muscle actin (SMA) to control for variations in CVSMC content. NEP activity was reduced in CAA, in both controls and AD. In leptomeningeal vessels, NEP activity was related to APOE genotype, being highest in ε2-positive and lowest in ε4-positive brains. To assess the role of NEP in protecting CVSMCs from Aβ toxicity, we measured cell death in primary human adult CVSMCs exposed to Aβ(1-40) , Aβ(1-42) or Aβ(1-40(Dutch variant)) . Aβ(1-42) was most cytotoxic to CVSMCs. Aβ(1-42) -mediated cell death was increased following siRNA-mediated knockdown or thiorphan-mediated inhibition of NEP activity; conversely Aβ(1-42) -mediated cytotoxicity was reduced by the addition of somatostatin and NEP over-expression following transfection with NEP cDNA. Our findings suggest that NEP protects CVSMCs from Aβ toxicity and protects cerebral blood vessels from the development and complications of CAA.

  4. Mirror Visual Feedback Induces Lower Neuromuscular Activity in Children with Spastic Hemiparetic Cerebral Palsy

    ERIC Educational Resources Information Center

    Feltham, Max G.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2010-01-01

    The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The "mirror box" creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two…

  5. Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice.

    PubMed

    Ray, R S; Rai, S; Katyal, A

    2014-12-01

    Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequalae, inducing loss of hippocampal neurons and behavioural deficits. Progressive neuronal death and memory dysfunctions culminate from several different mechanisms like oxidative stress, excitotoxicity, neuroinflammation and cholinergic hypofunction. Experimental evidences point to the beneficial effects of cholinomimetic agents such as rivastigmine and galantamine in improving memory outcomes following GCI/R injury. However, the direct implications of muscarinic and nicotinic receptor blockade during global cerebral ischemia/reperfusion injury have not been investigated. Therefore, we evaluated the relative involvement of muscarinic and nicotinic receptors in spatial/associative memory functions and neuronal damage during global cerebral ischemia reperfusion injury. The outcomes of present study support the idea that preservation of both muscarinic and nicotinic receptor functions is essential to alleviate hippocampal neuronal death in CA1 region following global cerebral ischemia/reperfusion injury.

  6. Successful treatment of refractory cerebral oedema in ecstasy/cocaine-induced fulminant hepatic failure using a new high-efficacy liver detoxification device (FPSA-Prometheus).

    PubMed

    Kramer, Ludwig; Bauer, Edith; Schenk, Peter; Steininger, Rudolf; Vigl, Marion; Mallek, Reinhold

    2003-09-15

    Ecstasy-induced fulminant hepatic failure is associated with high mortality. If complicated by cerebral oedema, orthotopic liver transplantation is the only established treatment. We report a case of combined ecstasy/cocaine-induced fulminant hepatic failure presenting with severe rhabdomyolysis, myocardial infarction and multiorgan failure. Transplantation was declined by the transplant surgeons because of a history of intravenous drug abuse. As excessive hyperammonaemia (318 mumol/l) and refractory transtentorial herniation developed, treatment with a new liver detoxification device combining high-flux haemodialysis and adsorption (FPSA-Prometheus) was initiated. Within a few hours of treatment, ammonia levels normalised. Cerebral oedema was greatly reduced by day 4 and hepatic function gradually recovered. Following neurologic rehabilitation for ischaemic sequelae of herniation, the patient was discharged from hospital with only minimal deficits. In conclusion, efficient extracorporeal detoxification may be an option for reversal of hyperammonaemia and refractory cerebral oedema in ecstasy/cocaine-induced acute liver failure.

  7. Intracerebral Glycine Administration Impairs Energy and Redox Homeostasis and Induces Glial Reactivity in Cerebral Cortex of Newborn Rats.

    PubMed

    Moura, Alana Pimentel; Parmeggiani, Belisa; Grings, Mateus; Alvorcem, Leonardo de Moura; Boldrini, Rafael Mello; Bumbel, Anna Paula; Motta, Marcela Moreira; Seminotti, Bianca; Wajner, Moacir; Leipnitz, Guilhian

    2016-11-01

    Accumulation of glycine (GLY) is the biochemical hallmark of glycine encephalopathy (GE), an aminoacidopathy characterized by severe neurological dysfunction that may lead to early death. In the present study, we evaluated the effect of a single intracerebroventricular administration of GLY on bioenergetics, redox homeostasis, and histopathology in brain of neonatal rats. Our results demonstrated that GLY decreased the activities of the respiratory chain complex IV and creatine kinase, induced reactive species generation, and diminished glutathione (GSH) levels 1, 5, and 10 days after GLY injection in cerebral cortex of 1-day-old rats. GLY also increased malondialdehyde (MDA) levels 5 days after GLY infusion in this brain region. Furthermore, GLY differentially modulated the activities of superoxide dismutase, catalase, and glutathione peroxidase depending on the period tested after GLY administration. In contrast, bioenergetics and redox parameters were not altered in brain of 5-day-old rats. Regarding the histopathological analysis, GLY increased S100β staining in cerebral cortex and striatum, and GFAP in corpus callosum of 1-day-old rats 5 days after injection. Finally, we verified that melatonin prevented the decrease of complex IV and CK activities and GSH concentrations, and the increase of MDA levels and S100β staining caused by GLY. Based on our findings, it may be presumed that impairment of redox and energy homeostasis and glial reactivity induced by GLY may contribute to the neurological dysfunction observed in GE.

  8. FNIRS-based evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy

    NASA Astrophysics Data System (ADS)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-03-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2 ± 2.1 years old) with hemiplegic cerebral palsy (CP) was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger tapping task were quantified before, immediately after, and six months after CIMT. Five age-matched healthy children (9.8 ± 1.3 years old) were also imaged at the same time points to provide comparative activation metrics for normal controls. In children with CP the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted six months later. In contrast to this longer term improvement in localized activation response, the laterality index that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed six months later.

  9. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    PubMed

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  10. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia

    PubMed Central

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8–24 h, whereas the late phase of BBB disruption begins 48–58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in

  11. Insulin-like growth factor 1 deficiency exacerbates hypertension-induced cerebral microhemorrhages in mice, mimicking the aging phenotype.

    PubMed

    Tarantini, Stefano; Valcarcel-Ares, Noa M; Yabluchanskiy, Andriy; Springo, Zsolt; Fulop, Gabor A; Ashpole, Nicole; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-03-14

    Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1(f/f)  + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment. In IGF-1-deficient mice, the same level of hypertension led to significantly earlier onset and increased incidence and neurological consequences of CMHs, as compared to control mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Previous studies showed that in aging, increased oxidative stress-mediated matrix metalloprotease (MMP) activation importantly contributes to the pathogenesis of CMHs. Thus, it is significant that hypertension-induced cerebrovascular oxidative stress and MMP activation were increased in IGF-1-deficient mice. We found that IGF-1 deficiency impaired hypertension-induced adaptive media hypertrophy and extracellular matrix remodeling, which together with the increased MMP activation likely also contributes to increased fragility of intracerebral arterioles. Collectively, IGF-1 deficiency promotes the pathogenesis of CMHs, mimicking the aging phenotype, which likely contribute to its deleterious effect on cognitive function. Therapeutic strategies that upregulate IGF-1 signaling in the cerebral vessels and/or reduce microvascular oxidative stress, and MMP activation may be useful for the prevention of CMHs, protecting cognitive function in high-risk elderly patients.

  12. Pilot Study of the Efficacy of Constraint-Induced Movement Therapy for Infants and Toddlers with Cerebral Palsy

    PubMed Central

    Lowes, Linda Pax; Mayhan, Marianne; Orr, Teresa; Batterson, Nancy; Tonneman, Jill Alyce; Meyer, Angela; Alfano, Lindsay; Wang, Wei; Whalen, Cara N; Nelin, Mary Ann; Lo, Warren David; Case-Smith, Jane

    2014-01-01

    The evidence for Constraint-Induced Movement Therapy (CIMT) effectiveness for infants and toddlers with unilateral cerebral palsy is minimal. We performed a pilot study of CIMT using one-month usual care, one-month intervention, and one-month maintenance (return to usual care) phases on five infants (7- to 18-month old). For the CIMT phase, the infants received 2 hr of occupational therapy and 1 hr of parent-implemented home program for five days/week. The infants were casted for the rst 23 days, and bimanual therapy was provided for the last three days. Fine motor skills for the more affected arm and gross motor skills improved significantly during the CIMT; these gains were maintained at one-month follow-up. Individual infant data show mixed effects. This pilot study provides initial evidence that CIMT is feasible for infants with unilateral cerebral palsy, and presents preliminary data for CIMT on fine and gross motor performance. PMID:23848499

  13. Cadmium-Induced Apoptosis in Primary Rat Cerebral Cortical Neurons Culture Is Mediated by a Calcium Signaling Pathway

    PubMed Central

    Xu, Hui; Sun, Ya; Hu, Fei-fei; Bian, Jian-chun; Liu, Xue-zhong; Gu, Jian-hong; Liu, Zong-ping

    2013-01-01

    Cadmium (Cd) is an extremely toxic metal, capable of severely damaging several organs, including the brain. Studies have shown that Cd disrupts intracellular free calcium ([Ca2+]i) homeostasis, leading to apoptosis in a variety of cells including primary murine neurons. Calcium is a ubiquitous intracellular ion which acts as a signaling mediator in numerous cellular processes including cell proliferation, differentiation, and survival/death. However, little is known about the role of calcium signaling in Cd-induced apoptosis in neuronal cells. Thus we investigated the role of calcium signaling in Cd-induced apoptosis in primary rat cerebral cortical neurons. Consistent with known toxic properties of Cd, exposure of cerebral cortical neurons to Cd caused morphological changes indicative of apoptosis and cell death. It also induced elevation of [Ca2+]i and inhibition of Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities. This Cd-induced elevation of [Ca2+]i was suppressed by an IP3R inhibitor, 2-APB, suggesting that ER-regulated Ca2+ is involved. In addition, we observed elevation of reactive oxygen species (ROS) levels, dysfunction of cytochrome oxidase subunits (COX-I/II/III), depletion of mitochondrial membrane potential (ΔΨm), and cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) during Cd exposure. Z-VAD-fmk, a pan caspase inhibitor, partially prevented Cd-induced apoptosis and cell death. Interestingly, apoptosis, cell death and these cellular events induced by Cd were blocked by BAPTA-AM, a specific intracellular Ca2+ chelator. Furthermore, western blot analysis revealed an up-regulated expression of Bcl-2 and down-regulated expression of Bax. However, these were not blocked by BAPTA-AM. Thus Cd toxicity is in part due to its disruption of intracellular Ca2+ homeostasis, by compromising ATPases activities and ER-regulated Ca2+, and this elevation in Ca2+ triggers the activation of the Ca2+-mitochondria apoptotic signaling pathway. This

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  15. Ethanol induces rapid lipid peroxidation and activation of nuclear factor-kappa B in cerebral vascular smooth muscle: relation to alcohol-induced brain injury in rats.

    PubMed

    Altura, Burton M; Gebrewold, Asefa; Zhang, Aimin; Altura, Bella T

    2002-06-07

    The present study was designed to test the hypothesis that acute administration of alcohol (ethanol) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, inhibition of IkappaB phosphorylation, and inhibition of nuclear transcription factor-kappa B (NF-kappaB). Ethanol (10, 25, 100 mM) resulted in concentration-dependent rises in malondialdehyde in as little as 30-45 min after exposure to the alcohol, rising to levels 2.5-10x normal after 18-24 h. Using EMSA assays and specific antibodies, ethanol caused three DNA-binding proteins (p50, p65, c-Rel) to rise in nuclear extracts in a concentration-dependent manner. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by ethanol (in a concentration-dependent manner) and inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These new biochemical and molecular data indicate that ethanol, even in physiologic concentrations, can elicit rapid lipid peroxidation and activation of NF-kappaB in cerebral vascular muscle cells. The present results when viewed in light of other recently published data suggest that ethanol-induced lipid peroxidation and activation of nuclear transcription factors probably play important roles in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

  16. Effects of Home-Based Constraint-Induced Therapy versus Dose-Matched Control Intervention on Functional Outcomes and Caregiver Well-Being in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

    2011-01-01

    This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21…

  17. Logistic Regression Analyses for Predicting Clinically Important Differences in Motor Capacity, Motor Performance, and Functional Independence after Constraint-Induced Therapy in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Shieh, Jeng-yi; Lu, Lu; Lin, Keh-chung

    2013-01-01

    Given the growing evidence for the effects of constraint-induced therapy (CIT) in children with cerebral palsy (CP), there is a need for investigating the characteristics of potential participants who may benefit most from this intervention. This study aimed to establish predictive models for the effects of pediatric CIT on motor and functional…

  18. Motor Learning Curve and Long-Term Effectiveness of Modified Constraint-Induced Movement Therapy in Children with Unilateral Cerebral Palsy: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Geerdink, Yvonne; Aarts, Pauline; Geurts, Alexander C.

    2013-01-01

    The goal of this study was to determine the progression of manual dexterity during 6 weeks (54 h) (modified) constraint-induced movement therapy ((m)CIMT) followed by 2 weeks (18 h) bimanual training (BiT) in children with unilateral spastic cerebral palsy (CP), to establish whether and when a maximal training effect was reached and which factors…

  19. Chromaffin cell grafts to rat cerebral cortex reverse lesion-induced memory deficits.

    PubMed

    Welner, S A; Koty, Z C; Boksa, P

    1990-09-10

    Adrenal chromaffin cells were isolated from donor adult rats and transplanted to the cerebral cortex of bilaterally nucleus basalis magnocellularis-lesioned rats. Chromaffin cell grafts to lesioned animals completely reversed the spatial memory deficit seen in lesioned alone animals on a T-maze alternation task. Although chromaffin cell grafts have been used previously to reverse motor abnormalities arising from defective nigro-striatal aminergic transmission, the present report is the first evidence that chromaffin cell transplants can reverse deficits in memory function. Grafts also enhanced cortical acetylcholinesterase staining.

  20. Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol

    PubMed Central

    Chen, Shih-Cheng; Yang, Ming-Hui; Chung, Tze-Wen; Jhuang, Ting-Syuan; Yang, Jean-Dean; Chen, Ko-Chin; Chen, Wan-Jou; Huang, Ying-Fong; Jong, Shiang-Bin; Tsai, Wan-Chi; Lin, Po-Chiao

    2017-01-01

    Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells. PMID:28127555

  1. Effects of Nigella sativa on apoptosis and GABAA receptor density in cerebral cortical and hippocampal neurons in pentylenetetrazol induced kindling in rats.

    PubMed

    Meral, I; Esrefoglu, M; Dar, K A; Ustunova, S; Aydin, M S; Demirtas, M; Arifoglu, Y

    2016-11-01

    We investigated the effects of Nigella sativa on apoptosis and gamma-aminobutyric acid (GABAA) receptor density in cerebral cortical and hippocampal neurons in a pentylenetetrazol (PTZ)-induced kindling model in rats. The PTZ kindling model was produced by injecting PTZ in subconvulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22 and 24 of the study into animals of PTZ treated (PTZ) and PTZ + N. sativa treated (PTZ + NS) groups. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the PTZ + NS group were treated also with a 10 mg/kg methanolic extract of N. sativa 2 h before each PTZ injection. Rats in the control group were treated with 4 ml/kg saline. The number of neurons that expressed GABAA receptors in the hippocampus and cerebral cortex of rats in the PTZ and PTZ + NS groups increased significantly. There was no significant difference in the number of GABAA receptors between the PTZ and PTZ + NS groups. GABAA receptor density of the neurons in the cerebral cortex, but not hippocampus, was increased in PTZ group compared to controls. We observed a significant increase in the number of apoptotic neurons in the cerebral cortex of rats of both the PTZ and PTZ + NS groups compared to controls. We observed a significant decrease in the number of the apoptotic neurons in the cerebral cortex of rats in the PTZ + NS group compared to the PTZ group. N. sativa treatment ameliorated the PTZ induced neurodegeneration in the cerebral cortex as reflected by neuronal apoptosis and neuronal GABAA receptor frequency.

  2. Cerebral venous sinus thrombosis with cerebral hemorrhage during early pregnancy

    PubMed Central

    Nie, Quanmin; Guo, Pin; Ge, Jianwei; Qiu, Yongming

    2015-01-01

    Cerebral venous sinus thrombosis (CVST) rarely induces cerebral hemorrhage, and CVST with cerebral hemorrhage during early pregnancy is extremely rare. Upon literature review, we are able to find only one case of CVST with cerebral hemorrhage in early pregnancy. In this paper, we report another case of a 27-year-old patient who developed CVST with cerebral hemorrhage in her fifth week of pregnancy. Although the optimal treatment for this infrequent condition remains controversial, we adopted anticoagulation as the first choice of treatment and obtained favorable results. PMID:25630781

  3. Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

    SciTech Connect

    Gozukirmizi, E.; Meyer, J.S.; Okabe, T.; Amano, T.; Mortel, K.; Karacan, I.

    1982-01-01

    Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significance was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements.

  4. Dexmedetomidine Protects against Transient Global Cerebral Ischemia/Reperfusion Induced Oxidative Stress and Inflammation in Diabetic Rats

    PubMed Central

    Xing, Xichun; Wang, Qi; Li, Wenzhi

    2016-01-01

    Background Transient global cerebral ischemia/reperfusion (I/R) is a major perioperative complication, and diabetes increases the response of oxidative stress and inflammation induced by I/R. The objective of this study was to determine the protective effect of dexmedetomidine against transient global cerebral ischemia/reperfusion induced oxidative stress and inflammation in diabetic rats. Methods Sixty-four rats were assigned into four experimental groups: normoglycemia, normoglycemia + dexmedetomidine, hyperglycemia, and hyperglycemia + dexmedetomidine and all subsequent neurological examinations were evaluated by a blinded observer. Damage to the brain was histologically assessed using the TUNEL staining method while western blotting was used to investigate changes in the expression levels of apoptosis-related proteins as well as the microglia marker, ionized calcium-binding adapter molecule 1 (Iba1). Water content in the brain was also analyzed. In addition, hippocampal concentrations of malondialdehyde (MDA) and Nox2 (a member of the Nox family of NADPH oxidases), and the activity of superoxide dismutase and catalase were analyzed. Finally, changes in serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were detected. Results Results showed that diabetes increased brain water content, the number of apoptotic neurons, early neurological deficit scores, oxidative stress (MDA and Nox2) and inflammation (pro-inflammatory cytokines including TNF-α and IL-6) levels following transient global I/R injury, but that these symptoms were attenuated following administration of dexmedetomidine. Conclusions These findings suggest that dexmedetomidine can significantly alleviate damage resulting from I/R, and this mechanism may be related to a reduction in both oxidative stress and inflammation which is normally associated with I/R. PMID:26982373

  5. Medium- and long-term effects of repeated bicuculline-induced seizures in developing rats on local cerebral energy metabolism.

    PubMed

    Doriat, J F; Koziel, V; Humbert, A C; Daval, J L

    1998-07-27

    To assess long-term metabolic consequences of recurrent ictal events arising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i.p. injections of bicuculline for three consecutive days, starting from postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cerebral metabolic rates for glucose were measured in 74 structures at P15, P25 and in adults (P60), by the autoradiographic method using 2-D-[14C]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reduction (16-34%) of glucose consumption at P15, mainly significant in sensory, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%). Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced metabolic rates for glucose (by 7-27%) at P25, significant in 23 structures, and depicting pronounced changes in limbic, hypothalamic, sensory and white matter areas, whereas brain functional activity finally returned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older animals, the reverse was true for long-term metabolic effects, and the more immature the brain when seizures arise, the more persistent the functional consequences.

  6. Reversible short-term and delayed long-term cognitive impairment induced by chronic mild cerebral hypoperfusion in rats.

    PubMed

    Thong-asa, Khwanjai; Chompoopong, Supin; Tantisira, Mayuree H; Tilokskulchai, Kanokwan

    2013-08-01

    Chronic cerebral hypoperfusion induced by aging in combination with vascular disorder potentially contributes to the development of vascular dementia. This study aimed to investigate the age-related changes in spatial performances in chronic mild cerebral hypoperfusion induced by permanent right common carotid artery occlusion (rCCAO) in rats. Four-month-old male Sprague-Dawley rats (n = 20) were randomly assigned into sham and rCCAO groups. Spatial performances of young adult rats (age 4-8 months) were evaluated repeatedly by the radial arm water maze at 6 days, and 1, 2 and 4 months after surgery. The spatial performance was re-assessed by the Morris water maze when the rats were 18 months old. The present results revealed that the rCCAO rats developed progressive deficit in spatial learning and memory, starting from day 6 and significant deficit was found at 2 months after rCCAO (p < 0.05). However, the spatial performance of the rCCAO rats was recovered at 4 months after surgery. Testing of the cognitive flexibility of the aged rCCAO rats (18 months old), indicated that the learning flexibility of the aged rCCAO rats was significantly impaired. This deficit was found in parallel with pronounced white matter damage in the corpus callosum and internal capsule and significant cell death in the dorsal hippocampus. Our results suggested that vascular risk insult in young adult rats resulted in spatial learning deficit which could be completely compensated later on. However, such previous vascular risk could be exacerbated by advancing age and subsequently lead to a deficit in cognitive flexibility with white matter damage and significant neuronal death in the dorsal hippocampus.

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

    PubMed

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

    2015-10-01

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

  8. Cognitive Improvement Induced by Environment Enrichment in Chronic Cerebral Hypoperfusion Rats: a Result of Upregulated Endogenous Neuroprotection?

    PubMed

    Yang, Ying; Zhang, Junjian; Xiong, Li; Deng, Min; Wang, Jing; Xin, Jiawei; Liu, Hui

    2015-06-01

    Environment enrichment (EE) has been demonstrated to improve the cognitive impairment that is induced by chronic cerebral hypoperfusion (CCH), but the underlying mechanism has not yet been elucidated. This study aimed to investigate the role of endogenous neuroprotection in EE-induced cognitive improvement in rats with CCH. Permanent bilateral common carotid artery occlusions (2-vessel occlusions (2VOs)) were performed to induce CCH in male adult Wistar rats. Four weeks after the surgeries, the rats were exposed to enriched environments for 4 weeks (6 h/day). Subsequently, we assessed the effects of EE on cognitive function, brain histone acetylation levels, neuroprotection-related transcription factors (i.e., cAMP response element-binding protein (CREB), phospho-CREB (p-CREB), hypoxia-inducible factor 1 (HIF-1) α, and nuclear regulatory factor 2 (Nrf2)), and oxidative stress and histological changes in the brain. After 2VO, the rats exposed to the EE treatment exhibited increased acetylation of histone 4 and increased p-CREB and Nrf2 protein levels in the brain. HIF-1α levels were increased after 2VO and reduced after EE treatment. The oxidative damage, histopathological changes in the brain, and spatial learning and memory impairments induced by 2VO were subsequently restored after EE treatment. These data indicate that EE promotes the acetylation of histone 4, regulates some neuroprotection-related transcription factors, attenuates oxidative damage, and protects against the histopathological damage to the brain induced by CCH. Together, the effects of EE in CCH rats might contribute to the recovery of spatial learning and memory.

  9. cPKCγ membrane translocation is involved in herkinorin-induced neuroprotection against cerebral ischemia/reperfusion injury in mice

    PubMed Central

    Gui, Xiaochen; Cui, Xu; Wei, Haiping; Feng, Guang; Zhang, Xuezheng; He, Yongjin; Li, Junfa; Li, Tianzuo

    2016-01-01

    Herkinorin is an opiate analgesic with limited adverse effects, functioning as a primary selective atypical opioid µ agonist. The present study aimed to identify whether herkinorin has a positive effect on ischemic/reperfusion (I/R) injury. Adult male C57BL/6 mice were randomly divided into five groups: i) Naïve, ii) sham, iii) I/R, iv) I/R with dimethyl sulfoxide (I/R+D) and v) I/R with herkinorin (I/R+H). The I/R injury model was induced by occluding the middle cerebral artery for 1 h followed by 24 h or 7 days of reperfusion. Neurobehavioral scores and sensorimotor functions were examined 24 h and 7 days following reperfusion. In addition, infarct volumes were examined at these time points using a 2,3,5-triphenyltetrazolium chloride assay. Herkinorin treatment improved neurobehavioral and sensorimotor functional recovery from I/R-induced brain injury. There was a significant decrease in infarct volume in the I/R+H group at 24 h or 7 days following reperfusion compared with the I/R and I/R+D groups. Western blotting suggested that the decrease in conventional protein kinase C γ (cPKCγ) membrane translocation in the peri-infarct region may be attenuated by herkinorin pretreatment. These results indicated that herkinorin may be beneficial in I/R-induced mouse brain injury, and this may be attributed to the membrane translocation of cPKCγ following activation. PMID:27922694

  10. PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window

    PubMed Central

    Shen, Zhe; Zheng, Yanrong; Wu, Jiaying; Chen, Ying; Wu, Xiaoli; Zhou, Yiting; Yuan, Yang; Lu, Shousheng; Jiang, Lei; Qin, Zhenghong; Chen, Zhong; Hu, Weiwei; Zhang, Xiangnan

    2017-01-01

    ABSTRACT Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons. Inhibition of mitophagy compromises neuroprotection conferred by APC. Furthermore, mitophagy and neuroprotection are abolished in Park2 knockout mice, indicating that APC-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria. Importantly, in MCAO mice, APC treatment extended the effective reperfusion window from 2 to 4 h, and this window was further extended to 6 h by exogenously expressing PARK2. Taken together, we found that PARK2-dependent APC-induced mitophagy renders the brain resistant to ischemic injury. APC treatment could be a favorable strategy to extend the thrombolytic time window for stroke therapy. PMID:28103118

  11. Effect of ST36 Acupuncture on Hyperventilation-Induced CO2 Reactivity of the Basilar and Middle Cerebral Arteries and Heart Rate Variability in Normal Subjects

    PubMed Central

    Jung, Woo-Sang; Cho, Ki-Ho; Kim, Young-Suk; Ko, Chang-Nam; Park, Jung-Mi; Moon, Sang-Kwan

    2014-01-01

    This study was conducted to verify the effect of acupuncture on cerebral haemodynamics to provide evidence for the use of acupuncture treatment as a complementary therapy for the high-risk stroke population. The effect of ST36 acupuncture treatment on the hyperventilation-induced CO2 reactivity of the basilar and middle cerebral arteries was studied in 10 healthy male volunteers (mean age, 25.2 ± 1.5 years) using a transcranial Doppler sonography with an interval of 1 week between measurements, and a portable ECG monitoring system was used to obtain ECG data simultaneously. The CO2 reactivity of the basilar and middle cerebral arteries increased significantly after ST36 acupuncture treatment, whereas the mean arterial blood pressure and pulse rate did not change significantly. The high-frequency power significantly increased after ST36 acupuncture treatment, and the percentage increase of high-frequency power correlated significantly with the percentage increase in the CO2 reactivity of the contralateral middle cerebral artery. These data suggest that ST36 acupuncture treatment increases CO2 reactivity, indicating improvement of vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions. The increase in parasympathetic tone by ST36 acupuncture treatment is responsible for this therapeutic effect. PMID:25132861

  12. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6.

    PubMed Central

    Campbell, I L; Abraham, C R; Masliah, E; Kemper, P; Inglis, J D; Oldstone, M B; Mucke, L

    1993-01-01

    Cytokines are thought to be important mediators in physiologic and pathophysiologic processes affecting the central nervous system (CNS). To explore this hypothesis, transgenic mice were generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS. A number of transgenic founder mice and their offspring exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression. Transgenic mice with high levels of IL-6 expression developed severe neurologic disease characterized by runting, tremor, ataxia, and seizure. Neuropathologic manifestations included neuro-degeneration, astrocytosis, angiogenesis, and induction of acute-phase-protein production. These findings indicate that cytokines such as IL-6 can have a direct pathogenic role in inflammatory, infectious, and neurodegenerative CNS diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7694279

  13. Network and external perturbation induce burst synchronisation in cat cerebral cortex

    NASA Astrophysics Data System (ADS)

    Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Batista, Antonio M.; Baptista, Murilo S.; Viana, Ricardo L.

    2016-05-01

    The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that burst synchronisation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.

  14. Cerebral haemodynamic response to acute intracranial hypertension induced by head-down tilt.

    PubMed

    Bosone, Daniele; Ozturk, Vesile; Roatta, Silvestro; Cavallini, Anna; Tosi, Piera; Micieli, Giuseppe

    2004-01-01

    The aim of this study was to evaluate, in a context of general inhibition of the sympathetic nervous system, the cerebral haemodynamic response to -30 degrees head-down tilt (HDT), a manoeuvre that produces an increase in intracranial arterial pressure. Nineteen healthy subjects were studied according to the following protocol: 10 min lying in supine position, 10 min HDT, 10 min recovery. Inhibition of the sympathetic system was confirmed by the decrease in heart rate (-3.6 bpm) and arterial blood pressure (-5.9 mmHg, p<0.05) in the late phase of the test. Blood velocity and blood pusatility index initially increased (+3.2 cm s(-1) and +9% respectively, p<0.01) then returned towards baseline before the end of HDT, while the cerebrovascular resistance index (=arterial blood pressure/blood velocity) dropped significantly and remained below control level (-7%, p<0.01) throughout the test. The changes in both these indices were opposite to those reported in several sympathetic activation tests, such as the handgrip and cold pressor tests. Conversely, arterial pressure at cranial level increased during HDT (as it also does during sympathetic activation tests), due to the development of a hydrostatic pressure gradient between heart and brain levels. Therefore, the effects observed on the pulsatility and resistance indices are not secondary to the increase in intracranial arterial pressure. It is suggested that the changes in these cerebrovascular indices are mediated by a reduction of sympathetic tone that presumably involves the cerebral as well as the peripheral vascular bed.

  15. Subfailure Overstretch Induces Persistent Changes in the Passive Mechanical Response of Cerebral Arteries

    PubMed Central

    Bell, E. David; Sullivan, Jacob W.; Monson, Kenneth L.

    2015-01-01

    Cerebral blood vessels are critical in maintaining the health of the brain, but their function can be disrupted by traumatic brain injury (TBI). Even in cases without hemorrhage, vessels are deformed with the surrounding brain tissue. This subfailure deformation could result in altered mechanical behavior. This study investigates the effect of overstretch on the passive behavior of isolated middle cerebral arteries (MCAs), with the hypothesis that axial stretch beyond the in vivo length alters this response. Twenty nine MCA sections from 11 ewes were tested. Vessels were subjected to a baseline test consisting of an axial stretch from a buckled state to 1.05* in vivo stretch (λIV) while pressurized at 13.3 kPa. Specimens were then subjected to a target level of axial overstretch between 1.05*λIV (λz = 1.15) and 1.52*λIV (λz = 1.63). Following overstretch, baseline tests were repeated immediately and then every 10 min, for 60 min, to investigate viscoelastic recovery. Injury was defined as an unrecoverable change in the passive mechanical response following overstretch. Finally, pressurized MCAs were pulled axially to failure. Post-overstretch response exhibited softening such that stress values at a given level of stretch were lower after injury. The observed softening also generally resulted in increased non-linearity of the stress-stretch curve, with toe region slope decreasing and large deformation slope increasing. There was no detectable change in reference configuration or failure values. As hypothesized, the magnitude of these alterations increased with overstretch severity, but only once overstretch exceeded 1.2*λIV (p < 0.001). These changes were persistent over 60 min. These changes may have significant implications in repeated TBI events and in increased susceptibility to stroke post-TBI. PMID:25674561

  16. Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats.

    PubMed

    Morel, Jean-Luc; Dabertrand, Fabrice; Porte, Yves; Prevot, Anne; Macrez, Nathalie

    2014-08-01

    Microgravity induces a redistribution of blood volume. Consequently, astronauts' body pressure is modified so that the upright blood pressure gradient is abolished, thereby inducing a modification in cerebral blood pressure. This effect is mimicked in the hindlimb unloaded rat model. After a duration of 8 days of unloading, Ca2+ signals activated by depolarization and inositol-1,4,5-trisphosphate intracellular release were increased in cerebral arteries. In the presence of ryanodine and thapsigargin, the depolarization-induced Ca2+ signals remained increased in hindlimb suspended animals, indicating that Ca2+ influx and Ca2+-induced Ca2+ release mechanism were both increased. Spontaneous Ca2+ waves and localized Ca2+ events were also investigated. Increases in both amplitude and frequency of spontaneous Ca2+ waves were measured in hindlimb suspension conditions. After pharmacological segregation of Ca2+ sparks and Ca2+ sparklets, their kinetic parameters were characterized. Hindlimb suspension induced an increase in the frequencies of both Ca2+ localized events, suggesting an increase of excitability. Labeling with bodipy compounds suggested that voltage-dependent Ca2+ channels and ryanodine receptor expressions were increased. Finally, the expression of the ryanodine receptor subtype 1 (RyR1) was increased in hindlimb unloading conditions. Taken together, these results suggest that RyR1 expression and voltage-dependent Ca2+ channels activity are the focal points of the regulation of Ca2+ signals activated by vasoconstriction in rat cerebral arteries with an increase of the voltage-dependent Ca2+ influx.

  17. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    PubMed

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E

    2014-07-01

    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P < 0.01), and VSM calcium was 200 ± 20 nmol/l in PAs vs. 104 ± 15 nmol/l in MCAs (P < 0.01). In vessels permeabilized with Staphylococcus aureus α-toxin, PAs were not more sensitive to calcium, suggesting calcium sensitization was not at the level of the contractile apparatus. PAs were 30-fold more sensitive to the voltage-dependent calcium channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P < 0.01); however, electrophysiological properties of the VDCC were not different in VSM. PAs had little to no response to the calcium-activated potassium channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  18. Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia

    PubMed Central

    Pérez-Mato, M; Ramos-Cabrer, P; Sobrino, T; Blanco, M; Ruban, A; Mirelman, D; Menendez, P; Castillo, J; Campos, F

    2014-01-01

    Blood glutamate scavenging is a novel and attractive protecting strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. Glutamate oxaloacetate transaminase 1 (GOT1) activation by means of oxaloacetate administration has been used to reduce the glutamate concentration in the blood. However, the protective effect of the administration of the recombinant GOT1 (rGOT1) enzyme has not been yet addressed in cerebral ischemia. The aim of this study was to analyze the protective effect of an effective dose of oxaloacetate and the human rGOT1 alone and in combination with a non-effective dose of oxaloacetate in an animal model of ischemic stroke. Sixty rats were subjected to a transient middle cerebral artery occlusion (MCAO). Infarct volumes were assessed by magnetic resonance imaging (MRI) before treatment administration, and 24 h and 7 days after MCAO. Brain glutamate levels were determined by in vivo MR spectroscopy (MRS) during artery occlusion (80 min) and reperfusion (180 min). GOT activity and serum glutamate concentration were analyzed during the occlusion and reperfusion period. Somatosensory test was performed at baseline and 7 days after MCAO. The three treatments tested induced a reduction in serum and brain glutamate levels, resulting in a reduction in infarct volume and sensorimotor deficit. Protective effect of rGOT1 supplemented with oxaloacetate at 7 days persists even when treatment was delayed until at least 2 h after onset of ischemia. In conclusion, our findings indicate that the combination of human rGOT1 with low doses of oxaloacetate seems to be a successful approach for stroke treatment PMID:24407245

  19. Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

    PubMed Central

    Hu, Yue; Xiong, Liu-Lin; Zhang, Piao; Wang, Ting-Hua

    2017-01-01

    Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores. We demonstrated that the transplantation of BMSCs (passage 3) via the tail vein into the lung tissues attenuated lung injury. In order to elucidate the underlying molecular mechanisms, we analyzed the gene expression profiles in lung tissues from the rats with focal cerebral ischemia and transplanted with BMSCs using a Gene microarray. Moreover, the Gene Ontology database was employed to determine gene function. We found that the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) were downregulated in the BMSC transplantation groups, compared with the control group. These results suggested that BMSC transplantation may attenuate lung injury following focal cerebral ischemia and that this effect is associated with the downregulation of TGF-β, PDGF and the PI3K-AKT pathway. PMID:27922691

  20. Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation.

    PubMed

    Hu, Yue; Xiong, Liu-Lin; Zhang, Piao; Wang, Ting-Hua

    2017-01-01

    Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores. We demonstrated that the transplantation of BMSCs (passage 3) via the tail vein into the lung tissues attenuated lung injury. In order to elucidate the underlying molecular mechanisms, we analyzed the gene expression profiles in lung tissues from the rats with focal cerebral ischemia and transplanted with BMSCs using a Gene microarray. Moreover, the Gene Ontology database was employed to determine gene function. We found that the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) were downregulated in the BMSC transplantation groups, compared with the control group. These results suggested that BMSC transplantation may attenuate lung injury following focal cerebral ischemia and that this effect is associated with the downregulation of TGF-β, PDGF and the PI3K-AKT pathway.

  1. Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions.

    PubMed

    Sun, Cheng; Yin, Nuoya; Wen, Ruoxi; Liu, Wei; Jia, Yanxia; Hu, Ligang; Zhou, Qunfang; Jiang, Guibin

    2016-01-01

    The rapid development of silver nanoparticles (AgNPs) based products has raised increasing concerns in view of their potential hazardous risks to the environment and human health. The roles of the released silver ions in AgNPs induced cytotoxicities are being hotly debated. Using rat cerebral astrocytes, the neurotoxicological effects of AgNPs and silver ions were investigated. Acute toxicity based on Alamar Blue assay showed that silver ions were considerably more toxic than AgNPs. Comparative studies indicated that AgNPs increased caspase activities and induced cell apoptosis under cytotoxic level of exposures, while silver ions compromised cell membrane integrity and dominantly caused cell necrosis. Cellular internalization of silver provided the basis for the cytotoxicities of these two silver species. In contrast to silver ions, intracellular reactive oxygen species (ROS) generation occurred in time- and concentration-dependent manners in astrocytes upon AgNPs stimulation, which caused subsequent c-Jun N-terminal kinases (JNK) phosphorylation and promoted the programmed cell death. Non-cytotoxic level of AgNPs exposure increased multiple cytokines secretion from the astrocytes, indicating that AgNPs were potentially involved in neuroinflammation. This effect was independent of silver ions as well. The distinct toxicological effects caused by AgNPs and silver ions provided the solid proofs for the particle-specific effects which should be concerned regarding the accurate assessment of AgNPs exposure risks.

  2. Gallium nitride induces neuronal differentiation markers in neural stem/precursor cells derived from rat cerebral cortex.

    PubMed

    Chen, Chi-Ruei; Li, Yi-Chen; Young, Tai-Horng

    2009-09-01

    In the present study, gallium nitride (GaN) was used as a substrate to culture neural stem/precursor cells (NSPCs), isolated from embryonic rat cerebral cortex, to examine the effect of GaN on the behavior of NSPCs in the presence of basic fibroblast growth factor (bFGF) in serum-free medium. Morphological studies showed that neurospheres maintained their initial shape and formed many long and thick processes with the fasciculate feature on GaN. Immunocytochemical characterization showed that GaN could induce the differentiation of NSPCs into neurons and astrocytes. Compared to poly-d-lysine (PDL), the most common substrate used for culturing neurons, there was considerable expression of synapsin I for differentiated neurons on GaN, suggesting GaN could induce the differentiation of NSPCs towards the mature differentiated neurons. Western blot analysis showed that the suppression of glycogen synthase kinase-3beta (GSK-3beta) activity was one of the effects of GaN-promoted NSPC differentiation into neurons. Finally, compared to PDL, GaN could significantly improve cell survival to reduce cell death after long-term culture. These results suggest that GaN potentially has a combination of electric characteristics suitable for developing neuron and/or NSPC chip systems.

  3. Cerebral Palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  4. An experimental study on laser-induced suturing of venous grafts in cerebral revascularization surgery

    NASA Astrophysics Data System (ADS)

    Puca, Alfredo; Albanese, Alessio; Esposito, Giuseppe; Maira, Giulio; Rossi, Giacomo; Pini, Roberto

    2005-04-01

    To test laser-assisted high flow bypass in cerebral revascularization procedures, we set up an experimental model on rabbits which included harvesting a jugular vein graft and its implantation on the common carotid artery through a double end-to-side anastomosis. The study was carried out on 25 New Zealand rabbits by performing on each animal the proximal anastomosis using conventional suturing, while the distal one was obtained by means of low-power diode laser welding in association with the topical application of Indocyanine Green (ICG) solution to enhance local absorption of the laser light. After the procedure, the animals were subjected to a follow-up from 2 to 9 days. Bypass patency was evaluated by means of Doppler study. The vascular segments were excised and evaluated by histological and immunohistochemical examinations. Utilization of the diode laser was associated with a substantial shortening of the operative time, as well as with a more active endothelial regeneration process at the anastomotic site.

  5. Local cerebral hyperthermia induces spontaneous thrombosis and arteriolar constriction in the pia mater of the mouse

    NASA Astrophysics Data System (ADS)

    El-Sabban, Farouk; Fahim, Mohamed A.

    1995-06-01

    The effect of local cerebral hyperthermia on responses of pial microvessels of the mouse was investigated. A set protocol was followed, involving the performance of a craniotomy on anaesthetized animals and using intravital microscope-television closed circuitry. Controlled hyperthermic exposure was applied regionally by heating the brain surface with irrigating artificial cerebrospinal fluid. Microvascular responses such as changes in diameter, thrombosis and embolism were monitored and video-taped observations were further viewed and analysed. When both brain surface and core body temperatures were kept at 37° C, no changes in pial microvessels were noted. With core body temperature kept at 37° C and at a brain surface temperature of 43.1° C, passing emboli and arteriolar constriction were observed. A few minutes later, visible thrombosis was prevalent. Further spontaneous thrombo-embolic activity continued and at the end of a 50-min hyperthermic exposure, arterioles attained a constriction of 37%. Thrombus formation was sometimes massive enough to occlude fully the microvessel. The protocol followed in this study can be adopted to other small animal species and for a variety of experimental procedures involving hyperthermia and the pial microcirculation.

  6. Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion.

    PubMed

    Kirisattayakul, Woranan; Wattanathorn, Jintanaporn; Tong-Un, Terdthai; Muchimapura, Supaporn; Wannanon, Panakaporn; Jittiwat, Jinatta

    2013-01-01

    The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg(-1) was orally given to male Wistar rats (300-350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  7. Ventricular fibrillation-induced cardiac arrest in the rat as a model of global cerebral ischemia

    PubMed Central

    Dave, Kunjan R.; Della-Morte, David; Saul, Isabel; Prado, Ricardo; Perez-Pinzon, Miguel A.

    2013-01-01

    Cardiopulmonary arrest remains one of the leading causes of death and disability in Western countries. Although ventricular fibrillation (VF) models in rodents mimic the “square wave” type of insult (rapid loss of pulse and pressure) commonly observed in adult humans at the onset of cardiac arrest (CA), they are not popular because of the complicated animal procedure, poor animal survival and thermal injury. Here we present a modified, simple, reliable, ventricular fibrillation-induced rat model of CA that will be useful in studying mechanisms of CA-induced delayed neuronal death as well as the efficacy of neuroprotective drugs. CA was induced in male Sprague Dawley rats using a modified method of von Planta et al. In brief, VF was induced in anesthetized, paralyzed, mechanically ventilated rats by an alternating current delivered to the entrance of the superior vena cava into the heart. Resuscitation was initiated by administering a bolus injection of epinephrine and sodium bicarbonate followed by mechanical ventilation and manual chest compressions and countershock with a 10-J DC current. Neurologic deficit score was higher in the CA group compared to the sham group during early reperfusion periods, suggesting brain damage. Significant damage in CA1 hippocampus (21% normal neurons compared to control animals) was observed following histopathological assessment at seven days of reperfusion. We propose that this method of VF-induced CA in rat provides a tool to study the mechanism of CA-induced neuronal death without compromising heart functions. PMID:24187598

  8. Evaluation of near infrared spectroscopy for detecting the β blocker-induced decrease in cerebral oxygenation during hemodilution in a swine model.

    PubMed

    Kurita, Tadayoshi; Morita, Koji; Sato, Shigehito

    2015-12-01

    β blockers reduce cerebral oxygenation after acute hemodilution and may contribute to the incidence of stroke when used perioperatively. The goal of the study was to investigate whether cerebral tissue oxygenation using near infrared spectroscopy can detect the β blocker-induced decrease in cerebral oxygenation depending on the severity of hemodilution and/or the dose of β blockers. Animals were anesthetized with 2% isoflurane and randomly assigned to a landiolol or esmolol group. After baseline measurement, landiolol or esmolol was administered at 40 µg/kg/min for 20 min, increased to 200 µg/kg/min for 20 min, and then stopped. Hemodynamic and arterial variables and the tissue oxygenation index (TOI) were recorded at each β blocker dose. Two stages of hemodilution were sequentially induced by repeated hemorrhage of 600 ml (33% of estimated blood volume) and infusion of the same volume of hydroxyethylstarch. During each stage, landiolol or esmolol was similarly administered and measurements were made. Landiolol and esmolol both dose-dependently decreased heart rate, mean arterial pressure and cardiac output, depending on the severity of hemodilution. Landiolol at 40 µg/kg/min was almost equivalent in potency to 200 µg/kg/min esmolol for decreasing HR before hemodilution. Based on the TOI, short-acting β blockers reduced cerebral oxygenation in a dose-dependent manner during hemodilution, and oxygenation returned to the baseline level after drug infusion was stopped. TOI may be useful for identification of a decrease in cerebral oxygenation for patients receiving β blockade during surgery associated with major bleeding.

  9. cPKCγ membrane translocation is involved in herkinorin‑induced neuroprotection against cerebral ischemia/reperfusion injury in mice.

    PubMed

    Gui, Xiaochen; Cui, Xu; Wei, Haiping; Feng, Guang; Zhang, Xuezheng; He, Yongjin; Li, Junfa; Li, Tianzuo

    2017-01-01

    Herkinorin is an opiate analgesic with limited adverse effects, functioning as a primary selective atypical opioid µ agonist. The present study aimed to identify whether herkinorin has a positive effect on ischemic/reperfusion (I/R) injury. Adult male C57BL/6 mice were randomly divided into five groups: i) Naïve, ii) sham, iii) I/R, iv) I/R with dimethyl sulfoxide (I/R+D) and v) I/R with herkinorin (I/R+H). The I/R injury model was induced by occluding the middle cerebral artery for 1 h followed by 24 h or 7 days of reperfusion. Neurobehavioral scores and sensorimotor functions were examined 24 h and 7 days following reperfusion. In addition, infarct volumes were examined at these time points using a 2,3,5‑triphenyltetrazolium chloride assay. Herkinorin treatment improved neurobehavioral and sensorimotor functional recovery from I/R‑induced brain injury. There was a significant decrease in infarct volume in the I/R+H group at 24 h or 7 days following reperfusion compared with the I/R and I/R+D groups. Western blotting suggested that the decrease in conventional protein kinase C γ (cPKCγ) membrane translocation in the peri‑infarct region may be attenuated by herkinorin pretreatment. These results indicated that herkinorin may be beneficial in I/R‑induced mouse brain injury, and this may be attributed to the membrane translocation of cPKCγ following activation.

  10. Facilitation handlings induce increase in electromyographic activity of muscles involved in head control of cerebral palsy children.

    PubMed

    Simon, Anelise de Saldanha; do Pinho, Alexandre Severo; Grazziotin Dos Santos, Camila; Pagnussat, Aline de Souza

    2014-10-01

    This study aimed to investigate the electromyographic (EMG) activation of the main cervical muscles involved in the head control during two postures widely used for the facilitation of head control in children with Cerebral Palsy (CP). A crossover trial involving 31 children with clinical diagnosis of CP and spastic quadriplegia was conducted. Electromyography was used to measure muscular activity in randomized postures. Three positions were at rest: (a) lateral decubitus, (b) ventral decubitus on the floor and (c) ventral decubitus on the wedge. Handlings for facilitating the head control were performed using the hip joint as key point of control in two postures: (a) lateral decubitus and (b) ventral decubitus on wedge. All children underwent standardized handlings, performed by the same researcher with experience in the neurodevelopmental treatment. EMG signal was recorded from muscles involved in the head control (paraspinal and sternocleidomastoid muscles) in sagittal, frontal and transverse planes, at the fourth cervical vertebra (C4), tenth thoracic vertebra (T10) and sternocleidomastoid muscle (SCM) levels. The results showed a significant increase in muscle activation when handling was performed in the lateral decubitus at C4 (P<0.001), T10 (P<0.001) and SCM (P=0.02) levels. A significant higher muscle activation was observed when handling was performed in lateral decubitus when compared to ventral decubitus at C4 level (P<0.001). Handling in ventral decubitus also induced an increase in EMG activation at T10 (P=0.018) and SCM (P=0.004) levels but not at C4 level (P=0.38). In conclusion, handlings performed in both positions may induce the facilitation of head control, as evaluated by the activity of cervical and upper trunk muscles. Handling performed in lateral decubitus may induce a slightly better facilitation of head control. These findings contribute to evidence-based physiotherapy practice for the rehabilitation of severely spastic quadriplegic CP

  11. Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats.

    PubMed

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Duan, Dan; Du, Guo; Wang, Qingsong

    2016-03-15

    Synaptic dysfunction underlies cognitive deficits induced by chronic cerebral hypoperfusion (CCH). There are silent synapses in neural circuits, but the effect of CCH on silent synapses is unknown. The present study was designed to explore learning and memory deficits and dynamic changes in silent synapses by direct visualization in a rat model of CCH. Adult male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to reproduce CCH. Learning and memory effects were examined at 1, 4, 12, and 24 weeks after BCCAO. In addition, immunofluorescent confocal microscopy was used to detect AMPA and N-methyl-d-aspartate receptors colocalized with synaptophysin, and Golgi-Cox staining was used to observe dendritic spine density. We found that BCCAO rats exhibited recognition memory deficits from 4 weeks; spatial learning and memory, as well as working memory impairment began at 1 week and persistent to 24 weeks after surgery. Following BCCAO, the percentage of silent synapses increased by 29.81-55.08% compared with the controls at different time points (P<0.001). Compared with control groups, dendritic spine density in the CA1 region of BCCAO groups significantly decreased (P<0.001). Thus, the present study suggests that CCH can induce long-lasting cognitive deficits and long-term increase in the number of silent synapses. Furthermore, the decrease in dendritic spine density was correlated with the decrease in the number of functional synapses. The results suggest a potential mechanism by which CCH can induce learning and memory deficits.

  12. Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat

    PubMed Central

    Nejad, Khojasteh Hoseiny; Gharib-Naseri, Mohammad Kazem; Sarkaki, Alireza; Dianat, Mahin; Badavi, Mohammad; Farbood, Yaghoub

    2017-01-01

    Objective(s): Global cerebral ischemia-reperfusion (GCIR) causes disturbances in brain functions as well as other organs such as kidney. Our aim was to evaluate the protective effects of ellagic acid (EA) on certain renal disfunction after GCIR. Materials and Methods: Adult male Wistar rats (n=32, 250-300 g) were used. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). Animal groups were: 1) received DMSO/saline (10%) as solvent of EA, 2) solvent + GCIR, 3) EA + GCIR, and 4) EA. Under anesthesia with ketamine/xylazine, GCIR was induced (20 and 30 min respectively) in related groups. EA (100 mg/kg, dissolved in DMSO/saline (10%) or solvent was administered (1.5 ml/kg) orally for 10 consecutive days to the related groups. EEG was recorded from NTS in GCIR treated groups. Results: Our data showed that: a) EEG in GCIR treated groups was flattened. b) GCIR reduced GFR (P<0.01) and pretreatment with EA attenuated this reduction. c) BUN was increased by GCIR (P<0.001) and pretreatment with EA improved the BUN to normal level. d) Serum creatinine concentration was elevated by GCIR but not significantly, however, in EA+GCIR group serum creatinine was reduced (P<0.05). e) GCIR induced proteinuria (P<0.05) but, EA was unable to reduced proteinuria. Conclusion: Results indicate that GCIR impairs certain renal functions and EA as an antioxidant can improve these functions. Our results suggest the possible usefulness of ellagic acid in patients with brain stroke. PMID:28133528

  13. Radiation-Induced Changes in Normal-Appearing White Matter in Patients With Cerebral Tumors: A Diffusion Tensor Imaging Study

    SciTech Connect

    Nagesh, Vijaya Tsien, Christina I.; Chenevert, Thomas L.; Ross, Brian D.; Lawrence, Theodore S.; Junick, Larry; Cao Yue

    2008-03-15

    Purpose: To quantify the radiation-induced changes in normal-appearing white matter before, during, and after radiotherapy (RT) in cerebral tumor patients. Methods and Materials: Twenty-five patients with low-grade glioma, high-grade glioma, or benign tumor treated with RT were studied using diffusion tensor magnetic resonance imaging. The biologically corrected doses ranged from 50 to 81 Gy. The temporal changes were assessed before, during, and to 45 weeks after the start of RT. The mean diffusivity of water (), fractional anisotropy of diffusion, diffusivity perpendicular ({lambda}{sub perpendicular}) and parallel ({lambda}{sub parallel}) to white matter fibers were calculated in normal-appearing genu and splenium of the corpus callosum. Results: In the genu and splenium, fractional anisotropy decreased and , {lambda}{sub parallel}, {lambda}{sub -perpendicular} increased linearly and significantly with time (p < 0.01). At 45 weeks after the start of RT, {lambda}{sub -perpendicular} had increased {approx}30% in the genu and splenium, and {lambda}{sub parallel} had increased 5% in the genu and 9% in the splenium, suggesting that demyelination is predominant. The increases in {lambda}{sub perpendicular} and {lambda}{sub parallel} were dose dependent, starting at 3 weeks and continuing to 32 weeks from the start of RT. The dose-dependent increase in {lambda}{sub perpendicular} and {lambda}{sub parallel} was not sustained after 32 weeks, indicating the transition from focal to diffuse effects. Conclusion: The acute and subacute changes in normal-appearing white matter fibers indicate radiation-induced demyelination and mild structural degradation of axonal fibers. The structural changes after RT are progressive, with early dose-dependent demyelination and subsequent diffuse dose-independent demyelination and mild axonal degradation. Diffusion tensor magnetic resonance imaging is potentially a biomarker for the assessment of radiation-induced white matter injury.

  14. Simultaneous Imaging of Radiation-Induced Cerebral Microbleeds, Arteries and Veins, Using a Multiple Gradient Echo Sequence at 7 Tesla

    PubMed Central

    Bian, Wei; Banerjee, Suchandrima; Kelly, Douglas A.C.; Hess, Christopher P.; Larson, Peder E.Z.; Chang, Susan M.; Nelson, Sarah J.; Lupo, Janine M.

    2016-01-01

    Background The purpose of this study was to implement and evaluate the utility of a multi-echo sequence at 7 Tesla (T) for simultaneous time-of-flight (TOF) MR-angiography (MRA) and susceptibility-weighted imaging (SWI) of radiation-induced cerebral microbleeds (CMBs), intracranial arteries, and veins. Methods A four-echo gradient-echo sequence was implemented on a 7T scanner. The first echo was used to create TOF-MRA images, while the remaining echoes were combined to visualize CMBs and veins on SWI images. The sequence was evaluated on eight brain tumor patients with known radiation-induced CMBs. Single-echo images were also acquired to visually and quantitatively compare the contrast-to-noise ratio (CNR) of small- and intermediate-vessels between acquisitions. The number of CMBs detected with each acquisition was also quantified. Statistical significance was determined using a Wilcoxon signed-rank test. Results Compared with the single-echo sequences, the CNR of small and intermediate arteries increased 7.6% (P < 0.03) and 9.5% (P = 0.06), respectively, while the CNR of small and intermediate veins were not statistically different between sequences (P = 0.95 and P = 0.46, respectively). However, these differences were not discernible by visual inspection. Also the multi-echo sequence detected 18.3% more CMBs (P < 0.008) due to higher slice resolution. Conclusion The proposed 7T multi-echo sequence depicts arteries, veins, and CMBs on a single image to facilitate quantitative evaluation of radiation-induced vascular injury. PMID:25471321

  15. Repeated edaravone treatment reduces oxidative cell damage in rat brain induced by middle cerebral artery occlusion.

    PubMed

    Yamamoto, Yorihiro; Yanagisawa, Makoto; Tak, Nyou Wei; Watanabe, Kazutoshi; Takahashi, Chizuko; Fujisawa, Akio; Kashiba, Misato; Tanaka, Masahiko

    2009-01-01

    The free radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) has been used to treat acute brain infarction in Japan since 2001. To obtain direct evidence that edaravone serves as an antioxidant in vivo, four groups of rats were prepared: (i) an ischemia/reperfusion (I/R) group receiving 2 h occlusion-reperfusion of the middle cerebral artery; (ii) a single administration group treated by intravenous infusion of edaravone (3 mg/kg) immediately after I/R; (iii) a repeated treatment group receiving twice daily edaravone administration for 14 days; and (iv) a sham operation group without occlusion. Repeated treatment with edaravone significantly improved the neurological symptoms and impairment of motor function as compared to the I/R group, while single administration demonstrated limited efficacy. No significant differences in plasma antioxidants such as ascorbate, urate, and vitamin E, or in redox status of coenzyme Q(9) were observed among the four groups. In contrast, the plasma content of oleic acid in the total free fatty acids (percentage 18:1) was significantly increased in the I/R group for 7 days as compared to the sham operation group. Oleic acid was produced from stearic acid by the action of stearoyl-CoA desaturase to compensate for the oxidative loss of polyunsaturated fatty acids. The above results suggest that cellular oxidative damage in the rat brain is evident for at least 7 days after I/R. Repeated treatment suppressed the percentage 18:1 increment, while the single administration did not, which is consistent with the limited efficacy of single administration.

  16. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.

    PubMed

    Kim, D H; Lee, H E; Kwon, K J; Park, S J; Heo, H; Lee, Y; Choi, J W; Shin, C Y; Ryu, J H

    2015-01-22

    Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. We found that early apoptotic cell death of the immature neurons occurred in the DG region following transient forebrain ischemia/reperfusion in mice. Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3β/β-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice.

  17. N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway.

    PubMed

    Zhang, Ping; Guo, Zhen-Fang; Xu, Yu-Ming; Li, Yu-Sheng; Song, Jing-Gui

    2016-10-01

    N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer's disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1β, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF.

  18. The use of EEG to measure cerebral changes during computer-based motion-sickness-inducing tasks

    NASA Astrophysics Data System (ADS)

    Strychacz, Christopher; Viirre, Erik; Wing, Shawn

    2005-05-01

    Motion sickness (MS) is a stressor commonly attributed with causing serious navigational and performance errors. The distinct nature of MS suggests this state may have distinct neural markers distinguishable from other states known to affect performance (e.g., stress, fatigue, sleep deprivation, high workload). This pilot study used new high-resolution electro-encephalograph (EEG) technologies to identify distinct neuronal activation changes that occur during MS. Brain EEG activity was monitored while subjects performed a ball-tracking task and viewed stimuli on a projection screen intended to induce motion sickness/spatial disorientation. Results show the presence of EEG spectral changes in all subjects who developed motion sickness when compared to baseline levels. These changes included: 1) low frequency (1 to 10 Hz) changes that may reflect oculomotor movements rather than intra-cerebral sources; 2) increased spectral power across all frequencies (attributable to increased scalp conductivity related to sweating), 3) local increases of power spectra in the 20-50 Hz range (likely attributable to external muscles on the skull) and; 4) a central posterior (occipital) independent component that shows suppression of a 20 Hz peak in the MS condition when compared to baseline. Further research is necessary to refine neural markers, characterize their origin and physiology, to distinguish between motion sickness and other states and to enable markers to be used for operator state monitoring and the designing of interventions for motion sickness.

  19. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  20. Astrocytic adaptation during cerebral angiogenesis follows the new vessel formation induced through chronic hypoxia in adult mouse cortex

    NASA Astrophysics Data System (ADS)

    Masamoto, Kazuto; Kanno, Iwao

    2014-03-01

    We examined longitudinal changes of the neuro-glia-vascular unit during cerebral angiogenesis induced through chronic hypoxia in the adult mouse cortex. Tie2-GFP mice in which the vascular endothelial cells expressed green fluorescent proteins (GFP) were exposed to chronic hypoxia, while the spatiotemporal developments of the cortical capillary sprouts and the neighboring astrocytic remodeling were characterized with repeated two-photon microscopy. The capillary sprouts appeared at early phases of the hypoxia adaptation (1-2 weeks), while the morphological changes of the astrocytic soma and processes were not detected in this phase. In the later phases of the hypoxia adaptation (> 2 weeks), the capillary sprouts created a new connection with existing capillaries, and its neighboring astrocytes extended their processes to the newly-formed vessels. The findings show that morphological adaptation of the astrocytes follow the capillary development during the hypoxia adaptation, which indicate that the newly-formed vessels provoke cellular interactions with the neighboring astrocytes to strengthen the functional blood-brain barrier.

  1. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    PubMed

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  2. High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes.

    PubMed

    Shah, Gul N; Morofuji, Yoichi; Banks, William A; Price, Tulin O

    2013-10-18

    Hyperglycemia-induced oxidative stress leads to diabetes-associated damage to the microvasculature of the brain. Pericytes in close proximity to endothelial cells in the brain microvessels are vital to the integrity of the blood-brain barrier and are especially susceptible to oxidative stress. According to our recently published results, streptozotocin-diabetic mouse brain exhibits oxidative stress and loose pericytes by twelve weeks of diabetes, and cerebral pericytes cultured in high glucose media suffer intracellular oxidative stress and apoptosis. Oxidative stress in diabetes is hypothesized to be caused by reactive oxygen species (ROS) produced during hyperglycemia-induced enhanced oxidative metabolism of glucose (respiration). To test this hypothesis, we investigated the effect of high glucose on respiration rate and ROS production in mouse cerebral pericytes. Previously, we showed that pharmacological inhibition of mitochondrial carbonic anhydrases protects the brain from oxidative stress and pericyte loss. The high glucose-induced intracellular oxidative stress and apoptosis of pericytes in culture were also reversed by inhibition of mitochondrial carbonic anhydrases. Therefore, we extended our current study to determine the effect of these inhibitors on high glucose-induced increases in pericyte respiration and ROS. We now report that both the respiration and ROS are significantly increased in pericytes challenged with high glucose. Furthermore, inhibition of mitochondrial carbonic anhydrases significantly slowed down both the rate of respiration and ROS production. These data provide new evidence that pharmacological inhibitors of mitochondrial carbonic anhydrases, already in clinical use, may prove beneficial in protecting the brain from oxidative stress caused by ROS produced as a consequence of hyperglycemia-induced enhanced respiration.

  3. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats.

    PubMed

    Awwad, Hibah O; Gonzalez, Larry P; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J; Awasthi, Vibhudutta; Standifer, Kelly M

    2015-01-01

    Physiological alterations, anxiety, and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI), and are common symptoms in service personnel exposed to blasts. Since 2006, 25,000-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined, following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p < 0.05; n = 8-11). Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using (18)F-fluorodeoxyglucose ((18)F-FDG). Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p < 0.05; n = 4-6) and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p < 0.05; n = 5-6).

  4. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury

    PubMed Central

    Andrews, Allison M.; Lutton, Evan M.; Merkel, Steven F.; Razmpour, Roshanak; Ramirez, Servio H.

    2016-01-01

    It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

  5. Biphasic Functional Regulation in Hippocampus of Rat with Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Common Carotid Artery

    PubMed Central

    Lee, In Sun; Han, Jung-Soo; Kim, Bu-Yeo

    2013-01-01

    Background Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO) in rats has been commonly used for the study of Alzheimer’s disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified. Methods Temporal changes (sham, 21, 35, 45, 55 and 70 days) in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO) and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO. Results Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01). Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01). In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis. Conclusions The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia. PMID:23936146

  6. Reduction of β-radiation exposure during preparation of 188Re-labelled Lipiodol for hepatocellular carcinoma treatment.

    PubMed

    Lepareur, Nicolas; Laffont, Sophie; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-02-01

    Rhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic.

  7. Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia.

    PubMed

    Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

    2016-01-01

    Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain.

  8. Neuroprotective effects of Salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro.

    PubMed

    Shi, Tian-yao; Feng, Shu-fang; Xing, Jiang-hao; Wu, Yu-mei; Li, Xiao-qiang; Zhang, Nan; Tian, Zhen; Liu, Shui-bing; Zhao, Ming-gao

    2012-05-01

    Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H(2)O(2)-induced neurotoxicity in vitro. Sal and Tyr significantly prevented a cerebral ischemic injury induced by a 2 h middle cerebral artery occlusion and a 24 h reperfusion in rats in vivo. Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after a 30 min exposure to 50 μM of H(2)O(2). Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and restored the balance of pro- and anti-apoptotic proteins. The neuroprotective effects of these two analogues show that Tyr has a better antioxidative action compared with Sal both in vivo and in vitro, and suggest that the antioxidant activity of Sal and Tyr may be partly due to their different substituents in their glycosyl groups. This gives a new insight into the development of therapeutic natural antioxidants against oxidative stress.

  9. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage.

    PubMed

    Sun, Kai; Fan, Jingyu; Han, Jingyan

    2015-01-01

    Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.

  10. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

    PubMed Central

    Sun, Kai; Fan, Jingyu; Han, Jingyan

    2015-01-01

    Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

  11. Morphine-induced changes in cerebral and cerebellar nitric oxide synthase activity.

    PubMed

    Leza, J C; Lizasoain, I; San-Martín-Clark, O; Lorenzo, P

    1995-10-04

    The effect of acute and chronic morphine treatment on nitric oxide (NO) synthase activity (determined by the rate of conversion of [14C]arginine into [14C]citrulline) on mouse brain was studied. Acute morphine treatment induced an increased in Ca2+ -dependent NO synthase in cerebellum. This effect was blocked by coadministration with naloxone. Chronic morphine treatment (by s.c. pellet) also produced an increase in cerebellar NO synthase, with a maximum on the second day of implantation. No significant changes were found in frontal cortex and forebrain during acute or chronic morphine treatment. The relationship between opiate effects and the L-arginine: NO pathway is discussed.

  12. The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

    PubMed Central

    Akpınar, Hatice; Nazıroğlu, Mustafa; Övey, İshak Suat; Çiğ, Bilal; Akpınar, Orhan

    2016-01-01

    Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 μg/kg) 3, 24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic calcium ion accumulation in the neurons, respectively. In addition, DEX completely reduced ISC-induced oxidative toxicity and apoptosis through intracellular reactive oxygen species production and depolarization of mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in the hippocampus and DRG. In conclusion, the current results are the first to demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation. Therefore, DEX can have remarkable neuroprotective impairment effects in the hippocampus and DRG of ISC-induced rats. PMID:27872485

  13. Role of thalamic nuclei in the modulation of Fos expression within the cerebral cortex during hypertonic saline-induced muscle nociception.

    PubMed

    Xiao, Y; Lei, J; Ye, G; Xu, H; You, H-J

    2015-09-24

    It has been proposed that thalamic mediodorsal (MD) and ventromedial (VM) nuclei form thalamic 'nociceptive discriminators' in discrimination of nociceptive afferents, and specifically govern endogenous descending facilitation and inhibition. The present study conducted in rats was to explore the role of thalamic MD and VM nuclei in modulation of cerebral neuronal activities by means of detection of spatiotemporal variations of Fos expression within the cerebral cortex. Following a unilateral intramuscular injection of 5.8% saline into the gastrocnemius muscle, Fos expression within the bilateral, different areas of the cerebral cortex except S2 was significantly increased (P<0.05). Particularly, the increases in Fos expression within the cingulate cortex and the insular cortex occurred at 0.5h, 4h and reached the peak level at 4h, 16h, respectively. Electrolytic lesion of the contralateral thalamic MD and VM nuclei significantly blocked the 5.8% saline intramuscularly induced increases in Fos expression within the bilateral cingulate and insular cortices, respectively. Additionally, the 5.8% saline-induced Fos expression in the cingulate cortex and the insular cortex were dose-dependently attenuated by microinjection of μ-opioid antagonist β-funaltrexamine hydrochloride into the thalamic MD and VM nuclei. It is suggested that (1) the neural circuits of 'thalamic MD nucleus - cingulate cortex' and 'thalamic VM nucleus - insular cortex' form two distinct pathways in the endogenous control of nociception, (2) mirror or contralateral pain is hypothesized to be related to cross-talk of neuronal activities within the bilateral cerebral cortices modulated by μ-opioid receptors within the thalamic MD and VM nuclei.

  14. Traumatic Brain Injury-Induced Ependymal Ciliary Loss Decreases Cerebral Spinal Fluid Flow

    PubMed Central

    Xiong, Guoxiang; Elkind, Jaclynn A.; Kundu, Suhali; Smith, Colin J.; Antunes, Marcelo B.; Tamashiro, Edwin; Kofonow, Jennifer M.; Mitala, Christina. M.; Stein, Sherman C.; Grady, M. Sean; Einhorn, Eugene; Cohen, Noam A.

    2014-01-01

    Abstract Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. In the present study, we investigated anatomical and functional alterations to mouse ventricular cilia that result from mild TBI. We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle. PMID:24749541

  15. Preparation of the core-shell structure adriamycin lipiodol microemulsions and their synergistic anti-tumor effects with diethyldithiocarbamate in vivo.

    PubMed

    Daocheng, Wu; Mingxi, Wan

    2010-11-01

    We prepared the core-shell structure adriamycin lipiodol microemulsions (ADM-CSLMs) and evaluated their in vivo antitumor effects in combination with Diethyldithiocarbamate (DDC). Two types of ADM-CSLMs, adriamycin liposome-lipiodol microemulsion(ADM-LLM) and adriamycin microsphere lipiodol microemulsion (ADM-MLM), were prepared through the emulsification method. The drug loading and encapsulation efficiency of ADM-CSLMs were measured by the high-performance liquid chromatograph (HPLC). The size and shape of the ADM-CSLMs were determined by an atom force microscopy (AFM), a transmission electron microscopy (TEM), and a particle size analyzer, respectively. The synergistic effects of DDC and ADM-CSLMs for cancer treatment of carcinoma drug-resistance cell was evaluated by the MTT method, the activation of superoxide dismutase (SOD) was detected by chemiluminescence, and the ADM accumulation in cells was measured by flow cytometry. Walker-256 carcinoma was transplanted to the livers of the male SD rats, ADM-CSLMs were administrated to the livers of the rats by intervention hepatic artery embolization through microsurgery. The tumor growth and animal survival were evaluated. The results show that the average diameter of ADM-LLM and ADM-MLM were 4.23 ± 1.2 μm and 4.67 ± 1.4 μm, respectively, and their ADM encapsulation efficiency were 83.7% and 87.2% with respect to loading efficiency of 82 μg/ml and 91 μg/ml. The tumor growth and animal survival in two of the ADM-CSLMs combined with DDC groups were significantly higher than that of ADM only treatment, ADM liposome combined with DDC (P < 0.01), as well as the ADM microsphere combined with DDC (P < 0.01). Therefore, ADM-CSLMs are useful carriers for the treatment of carcinoma and their anti-tumor effect can be enhanced by DDC in a suitable concentration.

  16. Intra-Arterial Rhenium-188 Lipiodol in the Treatment of Inoperable Hepatocellular Carcinoma: Results of an IAEA-Sponsored Multination Study

    SciTech Connect

    Bernal, Patricia; Raoul, Jean-Luc Vidmar, Gaj; Sereegotov, Erdenechimeg; Sundram, Felix X.; Kumar, Ajay; Jeong, Jae Min; Pusuwan, Pawana; Divgi, Chaitanya; Zanzonico, Pat; Stare, Janez; Buscombe, John; Chau Trinh Thi Minh; Saw, Maung Maung; Chen Shaoliang; Ogbac, Ruben; Padhy, Ajit K.

    2007-12-01

    Purpose: Intra-arterial injections (IAI) of 131I-lipiodol is effective in treating hepatocellular carcinoma patients, but is expensive and requires a 7-day hospitalization in a radioprotection room. 188Re is inexpensive, requires no patient isolation, and can be used with lipiodol. Methods and Materials: This International Atomic Energy Agency-sponsored phase II trial aimed to assess the safety and the efficacy of a radioconjugate 188Re + lipiodol (188Re-Lip) in a large cohort of hepatocellular carcinoma patients from developing countries. A scout dose is used to determine the maximal tolerated dose (lungs <12 Gy, normal liver <30 Gy, bone marrow <1.5 Gy) and then the delivery of the calculated activity. Efficacy was assessed using response evaluation criteria in solid tumor (RECIST) and alpha-feto-protein ({alpha}FP) levels and severe adverse events were graded using the Common Toxicity Criteria of the National Cancer Institute scale v2.0. Results: The trial included 185 patients from eight countries. The procedure was feasible in all participating centers. One treatment was given to 134 patients; 42, 8, and 1 received two, three, and four injections, respectively. The injected activity during the first treatment was 100 mCi. Tolerance was excellent. We observed three complete responses and 19 partial responses (22% of evaluable patients, 95% confidence interval 16-35%); 1- and 2-year survivals were 46% and 23%. Some factors affected survival: country of origin, existence of a cirrhosis, Cancer of the Liver Italian Program score, tumor dose, absence of progression, and posttreatment decrease in {alpha}FP level. Conclusions: IAI of 188Re-Lip in developing countries is feasible, safe, cost-effective, and deserves a phase III trial.

  17. [Viruses and the neuroendocrine system: model of murine obesity induced by cerebral infection by canine distemper virus].

    PubMed

    Bernard, A; Akaoka, H; Giraudon, P; Belin, M

    1999-05-01

    It is currently well established that the nervous, endocrine and immune systems inter-communicate using biologically active soluble factors, synthesised and produced by these three systems themselves (e.g. immunomodulator effect of hormones, effect of substances secreted by immune cells on endocrine function.). In addition, these systems jointly express receptors for hormones, peptides, growth factors and cytokines. Immuno-neuroendocrine interactions therefore underlie physiological processes and their deregulation can result in various pathological states. By entering into complex relationships with the specialized and differentiated cells of these three systems viruses can alter inter-cellular communication and result in the appearance of pathological processes directly linked to these disturbances. In order to understand the role of viruses in the genesis of neuroimmunoendocrine pathologies, we have developed a cerebral infection model using canine distemper virus (CDV). In infected mice, this paramyxovirus, closely related to the human measles virus, induces early neurological pathologies (encephalitis) which are associated with active viral replication. Mice surviving the acute phase of infection exhibit motor deficits (paralysis and turning behaviour) or obesity during the viral persistence phase, despite the fact that the virus is no longer detectable. The obesity is characterised by hyperinsulinaemia, hyperleptinaemia and hyperplasia of the adipocytes, associated with decreased expression of the OB-Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides. These results support the viral "hit and run" theory, since the initial viral impact in the hypothalamus may be the origin of the changes in later immunoneuroendocrine communication. Thus, certain human neurodegenerative or neuroendocrine diseases may have a previous viral infection aetiology without it being possible to clearly identify the agent responsible.

  18. Toward a theory of the general-anesthetic-induced phase transition of the cerebral cortex. I. A thermodynamics analogy.

    PubMed

    Steyn-Ross, M L; Steyn-Ross, D A; Sleigh, J W; Wilcocks, L C

    2001-07-01

    In a recent paper the authors developed a stochastic model for the response of the cerebral cortex to a general anesthetic agent. The model predicted that there would be an anesthetic-induced phase change at the point of transition into unconsciousness, manifested as a divergence in the electroencephalogram spectral power, and a change in spectral energy distribution from being relatively broadband in the conscious state to being strongly biased towards much lower frequencies in the unconscious state. Both predictions have been verified in recent clinical measurements. In the present paper we extend the model by calculating the equilibrium distribution function for the cortex, allowing us to establish a correspondence between the cortical phase transition and the more familiar thermodynamic phase transitions. This correspondence is achieved by first identifying a cortical free energy function, then by postulating that there exists an inverse relationship between an anesthetic effect and a quantity we define as cortical excitability, which plays a role analogous to temperature in thermodynamic phase transitions. We follow standard thermodynamic theory to compute a cortical entropy and a cortical "heat capacity," and we investigate how these will vary with anesthetic concentration. The significant result is the prediction that the entropy will decrease discontinuously at the moment of induction into unconsciousness, concomitant with a release of "latent heat" which should manifest as a divergence in the analogous heat capacity. There is clear clinical evidence of heat capacity divergence in historical anesthetic-effect measurements performed in 1977 by Stullken et al. [Anesthesiology 46, 28 (1977)]. The discontinuous step change in cortical entropy suggests that the cortical phase transition is analogous to a first-order thermodynamic transition in which the comatose-quiescent state is strongly ordered, while the active cortical state is relatively disordered.

  19. Toward a theory of the general-anesthetic-induced phase transition of the cerebral cortex. I. A thermodynamics analogy

    NASA Astrophysics Data System (ADS)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Sleigh, J. W.; Wilcocks, Lara C.

    2001-07-01

    In a recent paper the authors developed a stochastic model for the response of the cerebral cortex to a general anesthetic agent. The model predicted that there would be an anesthetic-induced phase change at the point of transition into unconsciousness, manifested as a divergence in the electroencephalogram spectral power, and a change in spectral energy distribution from being relatively broadband in the conscious state to being strongly biased towards much lower frequencies in the unconscious state. Both predictions have been verified in recent clinical measurements. In the present paper we extend the model by calculating the equilibrium distribution function for the cortex, allowing us to establish a correspondence between the cortical phase transition and the more familiar thermodynamic phase transitions. This correspondence is achieved by first identifying a cortical free energy function, then by postulating that there exists an inverse relationship between an anesthetic effect and a quantity we define as cortical excitability, which plays a role analogous to temperature in thermodynamic phase transitions. We follow standard thermodynamic theory to compute a cortical entropy and a cortical ``heat capacity,'' and we investigate how these will vary with anesthetic concentration. The significant result is the prediction that the entropy will decrease discontinuously at the moment of induction into unconsciousness, concomitant with a release of ``latent heat'' which should manifest as a divergence in the analogous heat capacity. There is clear clinical evidence of heat capacity divergence in historical anesthetic-effect measurements performed in 1977 by Stullken et al. [Anesthesiology 46, 28 (1977)]. The discontinuous step change in cortical entropy suggests that the cortical phase transition is analogous to a first-order thermodynamic transition in which the comatose-quiescent state is strongly ordered, while the active cortical state is relatively disordered.

  20. Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans

    PubMed Central

    Farmer, Adam D; Ban, Vin F; Coen, Steven J; Sanger, Gareth J; Barker, Gareth J; Gresty, Michael A; Giampietro, Vincent P; Williams, Steven C; Webb, Dominic L; Hellström, Per M; Andrews, Paul L R; Aziz, Qasim

    2015-01-01

    Abstract An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions. Key points Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although

  1. Flight-induced inhibition of the cerebral median peptidergic neurosecretory system in Locusta migratoria

    SciTech Connect

    Diederen, J.H.; van Etten, E.W.; Biegstraaten, A.I.; Terlou, M.; Vullings, H.G.; Jansen, W.F.

    1988-08-01

    This study discusses the effects of a 1-hr period of flight on the peptidergic pars intercerebralis (PI)-corpus cardiacum storage part (CCS) system in male Locusta migratoria, particularly the effect on material in this system stained by a histochemical method for peptidergic neurosecretory material (NSM) or labeled by in vivo incorporation of radioactive amino acid molecules. By use of an automatic image analysis system a number of parameters of the stained or radioactively labeled substances were measured to quantify the flight-induced effects and to get information on the manner in which the neurosecretory cell bodies in the PI and their axonal endings in the CCS accommodate changing amounts of NSM. The CCS of flown locusts contained distinctly more stained and radioactively labeled substances than the CCS of unflown locusts. A tendency to similar differences was observed in the cluster of neurosecretory cell bodies in the PI. The results indicate that 1 hr flight inhibited the release of NSM by the PI-CCS system. After the onset of reduced release activity by flight, some NSM continued to be synthesized and transported from the PI to the CCS, gradually filling up and expanding the entire PI-CCS system, the NSM at the same time becoming more and more densely packed. It is concluded that the peptidergic PI-CCS system is not actively involved in the control of flight metabolism or flight behavior.

  2. Muscle Recruitment and Coordination following Constraint-Induced Movement Therapy with Electrical Stimulation on Children with Hemiplegic Cerebral Palsy: A Randomized Controlled Trial

    PubMed Central

    Xu, Kaishou; He, Lu; Mai, Jianning; Yan, Xiaohua; Chen, Ying

    2015-01-01

    Objective To investigate changes of muscle recruitment and coordination following constraint-induced movement therapy, constraint-induced movement therapy plus electrical stimulation, and traditional occupational therapy in treating hand dysfunction. Methods In a randomized, single-blind, controlled trial, children with hemiplegic cerebral palsy were randomly assigned to receive constraint-induced movement therapy (n = 22), constraint-induced movement therapy plus electrical stimulation (n = 23), or traditional occupational therapy (n = 23). Three groups received a 2-week hospital-based intervention and a 6-month home-based exercise program following hospital-based intervention. Constraint-induced movement therapy involved intensive functional training of the involved hand during which the uninvolved hand was constrained. Electrical stimulation was applied on wrist extensors of the involved hand. Traditional occupational therapy involved functional unimanual and bimanual training. All children underwent clinical assessments and surface electromyography (EMG) at baseline, 2 weeks, 3 and 6 months after treatment. Surface myoelectric signals were integrated EMG, root mean square and cocontraction ratio. Clinical measures were grip strength and upper extremity functional test. Results Constraint-induced movement therapy plus electrical stimulation group showed both a greater rate of improvement in integrated EMG of the involved wrist extensors and cocontraction ratio compared to the other two groups at 3 and 6 months, as well as improving in root mean square of the involved wrist extensors than traditional occupational therapy group (p<0.05). Positive correlations were found between both upper extremity functional test scores and integrated EMG of the involved wrist as well as grip strength and integrated EMG of the involved wrist extensors (p<0.05). Conclusions Constraint-induced movement therapy plus electrical stimulation is likely to produce the best outcome in

  3. Warming Effect on Miriplatin-Lipiodol Suspension as a Chemotherapeutic Agent for Transarterial Chemoembolization for Hepatocellular Carcinoma: Preliminary Clinical Experience

    SciTech Connect

    Kora, Shinn-ichi; Urakawa, Hiroshi; Mitsufuji, Toshimichi; Osame, Akinobu; Higashihara, Hideyuki; Yoshimitsu, Kengo

    2013-08-01

    PurposeTo retrospectively elucidate the preliminary clinical impact of warmed miriplatin-lipiodol suspension (MPT-LPD) when used as a chemotherapeutic agent for transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Materials and MethodsBetween June and December 2010, TACE was performed with MPT-LPD at room temperature (RT group), and after January 2011, TACE with MPT-LPD warmed to 40 Degree-Sign C was performed (W group). The intraarterial appearance of MPT-LPD immediately after injection through microcatheters at the second-order branches was compared between the two groups with a 5-point grading system. Local therapeutic effects of HCCs as assessed by follow-up computed tomography (CT) obtained 1-3 months after TACE were compared between the groups with a 4-point grading system (TE1-TE4). After April 2011, angiography-assisted CT was routinely performed at TACE, and HCCs that revealed apparent corona enhancement (CE) were retrospectively selected. The degree of concordance between CE and MPT-LPD accumulation as assessed by CT immediately after TACE was assessed with a 3-point grading scale.ResultsMPT-LPD therapy resulted in a smooth and continuous appearance in the W group (grades 1, 2, 3, 4, and 5 were, respectively, 1, 2, 11, 18, and 4) compared to the RT group (4, 0, 1, 2, and 0). The W group (TE1, TE2, TE3, and TE4 were 1, 9, 11, and 12) revealed better local therapeutic effects than the RT group (6, 3, 9, and 0) (p < 0.05). CE was found in 26 HCC nodules, and concordance between CE and MPT-LPD accumulation was observed in 66 % (grades 1, 2, and 3 were, respectively, 2, 8, and 19).ConclusionWarmed MPT-LPD flowed more smoothly within vascular lumen, passed through tumor sinusoid of HCC, and had better local therapeutic effects at short-term observation than MPT-LPD at room temperature.

  4. Hemodynamic changes in a rat parietal cortex after endothelin-1-induced middle cerebral artery occlusion monitored by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Ma, Yushu; Dou, Shidan; Wang, Yi; La, Dongsheng; Liu, Jianghong; Ma, Zhenhe

    2016-07-01

    A blockage of the middle cerebral artery (MCA) on the cortical branch will seriously affect the blood supply of the cerebral cortex. Real-time monitoring of MCA hemodynamic parameters is critical for therapy and rehabilitation. Optical coherence tomography (OCT) is a powerful imaging modality that can produce not only structural images but also functional information on the tissue. We use OCT to detect hemodynamic changes after MCA branch occlusion. We injected a selected dose of endothelin-1 (ET-1) at a depth of 1 mm near the MCA and let the blood vessels follow a process first of occlusion and then of slow reperfusion as realistically as possible to simulate local cerebral ischemia. During this period, we used optical microangiography and Doppler OCT to obtain multiple hemodynamic MCA parameters. The change trend of these parameters from before to after ET-1 injection clearly reflects the dynamic regularity of the MCA. These results show the mechanism of the cerebral ischemia-reperfusion process after a transient middle cerebral artery occlusion and confirm that OCT can be used to monitor hemodynamic parameters.

  5. Cerebral blood flow and metabolism during cardiopulmonary bypass with special reference to effects of hypotension induced by prostacyclin

    SciTech Connect

    Feddersen, K.; Aren, C.; Nilsson, N.J.; Radegran, K.

    1986-04-01

    Cerebral blood flow and metabolism of oxygen, glucose, and lactate were studied in 43 patients undergoing aortocoronary bypass. Twenty-five patients received prostacyclin infusion, 50 ng per kilogram of body weight per minute, during cardiopulmonary bypass (CPB), and 18 patients served as a control group. Regional cerebral blood flow (CBF) was studied by intraarterially injected xenon 133 and a single scintillation detector. Oxygen tension, carbon dioxide tension, oxygen saturation, glucose, and lactate were measured in arterial and cerebral venous blood. Mean arterial blood pressure decreased during hypothermia and prostacyclin infusion to less than 30 mm Hg. The regional CBF was, on average, 22 (standard deviation (SD) 4) ml/100 gm/min before CPB. It increased in the control group during hypothermia to 34 (SD 12) ml/100 gm/min, but decreased in the prostacyclin group to 15 (SD 5) ml/100 gm/min. It increased during rewarming in the prostacyclin group. After CPB, regional CBF was about 40 ml/100 gm/min in both groups. The cerebral arteriovenous oxygen pressure difference decreased more in the control group than in the prostacyclin group during hypothermia. The cerebral metabolic rate of oxygen decreased in both groups from approximately 2 ml/100 gm/min to about 1 ml/100 gm/min during hypothermia, increased again during rewarming, and after CPB was at the levels measured before bypass in both groups. There was no difference between the groups in regard to glucose and lactate metabolism.

  6. Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression.

    PubMed

    Yan, Xiao-Jin; Chai, Yu-Shuang; Yuan, Zhi-Yi; Wang, Xin-Pei; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; DU, Li-Jun

    2016-05-01

    Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.

  7. Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: a microdialysis study.

    PubMed

    Shearman, E; Rossi, S; Szasz, B; Juranyi, Z; Fallon, S; Pomara, N; Sershen, H; Lajtha, A

    2006-03-31

    ventral tegmental area. Our results suggest both region and drug specific neurotransmitter effects of these agents as well as some similarities. We conclude that drugs influencing cognitive mechanisms induce changes in a number of neurotransmitters with the changes being both region and drug specific. Release and metabolism are altered and extracellular neurotransmitter levels can be increased or decreased by the drugs. Other studies are in progress to determine the pharmacological effects associated with chronic treatment with these compounds, which may be more pertinent to the clinical situation in which patients take these medications for months or years.

  8. Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle cell KCa channels

    PubMed Central

    Li, Anlong; Xi, Qi; Umstot, Edward S.; Bellner, Lars; Schwartzman, Michal L.; Jaggar, Jonathan H.; Leffler, Charles W.

    2012-01-01

    Astrocyte signals can modulate arteriolar tone, contributing to regulation of cerebral blood flow, but specific intercellular communication mechanisms are unclear. Here we used isolated cerebral arteriole myocytes, astrocytes, and brain slices to investigate whether carbon monoxide (CO) generated by the enzyme heme oxygenase (HO) acts as an astrocyte-to-myocyte gasotransmitter in the brain. Glutamate stimulated CO production by astrocytes with intact HO-2, but not those genetically deficient in HO-2. Glutamate activated transient KCa currents and single KCa channels in myocytes that were in contact with astrocytes, but did not affect KCa channel activity in myocytes that were alone. Pre-treatment of astrocytes with chromium mesoporphyrin (CrMP), a HO inhibitor, or genetic ablation of HO-2 prevented glutamate-induced activation of myocyte transient KCa currents and KCa channels. Glutamate decreased arteriole myocyte intracellular Ca2+ concentration and dilated brain slice arterioles and this decrease and dilation were blocked by CrMP. Brain slice arteriole dilation to glutamate was also blocked by L-2-alpha aminoadipic acid, a selective astrocyte toxin, and paxilline, a KCa channel blocker. These data indicate that an astrocytic signal, notably HO-2 derived CO, is employed by glutamate to stimulate arteriole myocyte KCa channels and dilate cerebral arterioles. Our study explains the astrocyte and HO dependence of glutamatergic functional hyperemia observed in the newborn cerebrovascular circulation in vivo. PMID:17991880

  9. Possible involvement of NO/NOS signaling in hippocampal amyloid-beta production induced by transient focal cerebral ischemia in aged rats.

    PubMed

    Li, Song; Wang, Wei; Wang, Che; Tang, Yi-Yuan

    2010-02-12

    In the present study, to define the roles of nitric oxide (NO) signaling in amyloid-beta (A beta) production after transient cerebral ischemia, extracellular levels of NO and A beta were monitored by intracerebral microdialysis in the hippocampus of aged rats exposed to transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results indicated that 1-h MCAO significantly upregulated hippocampal NO and A beta levels. In addition, the NO elevation preceded the A beta changes. The Western blotting suggested that acute hypoperfusion could increase the expression of beta-secretase 1 (BACE1) but not BACE2. The enhanced NO concentration in acute stage of MCAO/R was coincident with increased eNOS expression, while in subacute stage was coincident with increased iNOS and nNOS. Our results also indicated that pretreatment of L-NAME, one non-selective NOS inhibitor could decrease the BACE1 expression, reverse both NO and A beta changes and rescue the delayed neuronal death. These preliminary findings indicated that activation of NOS/NO signaling system could trigger A beta production through BACE1 pathway during acute ischemic episode. The present data may be important in understanding, at least in part, the pathological role of NO/NOS system involved in hippocampal A beta production and neuronal damage induced by transient cerebral ischemia.

  10. Electrical stimulation of cerebellar fastigial nucleus promotes the expression of growth arrest and DNA damage inducible gene β and motor function recovery in cerebral ischemia/reperfusion rats.

    PubMed

    Liu, Bin; Li, Jianrui; Li, Longling; Yu, Lehua; Li, Changqing

    2012-06-27

    This study focused on the effects of electrical stimulation of cerebellar fastigial nucleus on the expression of growth arrest and DNA damage inducible gene β (Gadd45β) and on motor function recovery after focal cerebral ischemia/reperfusion (I/R) in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham I/R (control group), I/R (I/R group), I/R with sham stimulation and I/R with electrical stimulation at 6h, 12h, 24h, 2d and 3d after I/R. Cerebral ischemia and reperfusion was established by nylon monofilament occlusion method. Fastigial nucleus (FN) electrical stimulation was applied at 2h after ischemia for 1h. The changes in the expression of Gadd45β were analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and Western-blot respectively. Another group of rats were divided into the same 4 groups. Montoya staircase test score was used to test the motor function of affected forelimb. The levels of Gadd45β were significantly elevated after I/R injury. FN electrical stimulation treatment elevated the expression of Gadd45β further and improved motor function recovery. These results suggest that FN electrical stimulation can promote the expression of Gadd45β and motor function recovery after focal cerebral ischemia.

  11. Diffusion Tensor Imaging Detects Early Cerebral Cortex Abnormalities in Neuronal Architecture Induced by Bilateral Neonatal Enucleation: An Experimental Model in the Ferret

    PubMed Central

    Bock, Andrew S.; Olavarria, Jaime F.; Leigland, Lindsey A.; Taber, Erin N.; Jespersen, Sune N.; Kroenke, Christopher D.

    2010-01-01

    Diffusion tensor imaging (DTI) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7) in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi-staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy. PMID:21048904

  12. Chotosan, a kampo formula, ameliorates chronic cerebral hypoperfusion-induced deficits in object recognition behaviors and central cholinergic systems in mice.

    PubMed

    Zhao, Qi; Murakami, Yukihisa; Tohda, Michihisa; Obi, Ryosuke; Shimada, Yutaka; Matsumoto, Kinzo

    2007-04-01

    We previously demonstrated that the Kampo formula chotosan (CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampo formula saikokeishito (SKT) were used as controls. P2VO impaired object discrimination performance in the object recognition, location, and context tests. Daily administration of CTS (750 mg/kg, p.o.) and THA (2.5 mg/kg, i.p.) improved the object discrimination deficits, whereas SKT (750 mg/kg, p.o.) did not. In ex vivo assays, tacrine but not CTS or SKT inhibited cortical cholinesterase activity. P2VO reduced the mRNA expression of m(3) and m(5) muscarinic receptors and choline acetyltransferase but not that of other muscarinic receptor subtypes in the cerebral cortex. Daily administration of CTS and THA but not SKT reversed these expression changes. These results suggest that CTS and THA improve P2VO-induced cognitive impairment by normalizing the deficit of central cholinergic systems and that the beneficial effect on P2VO-induced cognitive deficits is a distinctive pharmacological characteristic of CTS.

  13. Improved targeting of 5-[125I/131I]iodo-2‧-deoxyuridine to rat hepatoma by using lipiodol emulsion

    NASA Astrophysics Data System (ADS)

    Yu, Hung-Man; Yeh, Hsin-Pei; Chang, Tien-Kui; Huang, Kuang-Liang; Chuang, Kuo-Tang; Liu, Ren-Shen; Wang, Shyh-Jen; Hwang, Jeng-Jong; Chi, Kwan-Hwa; Chen, Fu-Du; Lin, Wuu-Jyh; Chen, Chin-Hsiung; Wang, Hsin-Ell

    2006-12-01

    This study aims to assess whether emulsion of [ 125/131I]IUdR and lipiodol (IUdR/LP) can improve delivery of IUdR into hepatoma. MethodsIn vitro release profile of IUdR from IUdR/LP to serum was performed. IUdR/LP was injected into N1-S1 hepatoma-bearing SD rat via hepatic artery and IUdR/normal saline (IUdR/NS) was used for comparison. Biodistribution, autoradiography, imaging and tumor DNA incorporation assay were performed. The radioactive metabolites in plasma and urine were analyzed. Radiation doses to tumor and organs were estimated. ResultsIUdR released from lipiodol into serum was fast. There were longer retention, more DNA incorporation and higher radiation dose of IUdR in the tumor by using IUdR/LP. IUdR/LP deposited deep in the hepatomas. Only free iodide was found in the plasma and urine after injection of IUdR/LP. ConclusionsHepatic artery injection of IUdR/LP emulsion could definitely enhance the tumor cell uptake and incorporation to DNA of *IUdR, prolong the tumor retention time and increase radiation dose to tumor. IUdR/LP may be an effective therapeutic agent for the treatment of hepatic tumors.

  14. [Cerebral ischemia and histamine].

    PubMed

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  15. Facilitating Mitochondrial Calcium Uptake Improves Activation-Induced Cerebral Blood Flow and Behavior after mTBI

    PubMed Central

    Murugan, Madhuvika; Santhakumar, Vijayalakshmi; Kannurpatti, Sridhar S.

    2016-01-01

    Mild to moderate traumatic brain injury (mTBI) leads to secondary neuronal loss via excitotoxic mechanisms, including mitochondrial Ca2+ overload. However, in the surviving cellular population, mitochondrial Ca2+ influx, and oxidative metabolism are diminished leading to suboptimal neuronal circuit activity and poor prognosis. Hence we tested the impact of boosting neuronal electrical activity and oxidative metabolism by facilitating mitochondrial Ca2+ uptake in a rat model of mTBI. In developing rats (P25-P26) sustaining an mTBI, we demonstrate post-traumatic changes in cerebral blood flow (CBF) in the sensorimotor cortex in response to whisker stimulation compared to sham using functional Laser Doppler Imaging (fLDI) at adulthood (P67-P73). Compared to sham, whisker stimulation-evoked positive CBF responses decreased while negative CBF responses increased in the mTBI animals. The spatiotemporal CBF changes representing underlying neuronal activity suggested profound changes to neurovascular activity after mTBI. Behavioral assessment of the same cohort of animals prior to fLDI showed that mTBI resulted in persistent contralateral sensorimotor behavioral deficit along with ipsilateral neuronal loss compared to sham. Treating mTBI rats with Kaempferol, a dietary flavonol compound that enhanced mitochondrial Ca2+ uptake, eliminated the inter-hemispheric asymmetry in the whisker stimulation-induced positive CBF responses and the ipsilateral negative CBF responses otherwise observed in the untreated and vehicle-treated mTBI animals in adulthood. Kaempferol also improved somatosensory behavioral measures compared to untreated and vehicle treated mTBI animals without augmenting post-injury neuronal loss. The results indicate that reduced mitochondrial Ca2+ uptake in the surviving populations affect post-traumatic neural activation leading to persistent behavioral deficits. Improvement in sensorimotor behavior and spatiotemporal neurovascular activity following kaempferol

  16. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.

    PubMed

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2013-03-01

    The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. Associative tuning plasticity in the primary auditory cortex (A1) constitutes a well-characterized candidate specific memory substrate that is ubiquitous across species, tasks and motivational states. When tone predicts reinforcement, the tuning of cells in A1 shifts toward or to the signal frequency within its tonotopic map, producing an over-representation of behaviorally important sounds. Tuning shifts have the cardinal attributes of forms of memory, including associativity, specificity, rapid induction, consolidation and long-term retention and are therefore likely memory representations. We hypothesized that the BLA strengthens memories by increasing their cortical representations. We recorded multiple unit activity from A1 of rats that received a single discrimination training session in which two tones (2.0 s) separated by 1.25 octaves were either paired with brief electrical stimulation (400 ms) of the BLA (CS+) or not (CS-). Frequency response areas generated by presenting a matrix of test tones (0.5-53.82 kHz, 0-70 dB) were obtained before training and daily for 3 weeks post-training. Tuning both at threshold and above threshold shifted predominantly toward the CS+ beginning on day 1. Tuning shifts were maintained for the entire 3 weeks. Absolute threshold and bandwidth decreased, producing less enduring increases in sensitivity and selectivity. BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the

  17. Sympathetically-induced changes in microvascular cerebral blood flow and in the morphology of its low-frequency waves.

    PubMed

    Deriu, F; Roatta, S; Grassi, C; Urciuoli, R; Micieli, G; Passatore, M

    1996-06-10

    The effect of bilateral cervical sympathetic nerve stimulation on microvascular cerebral blood flow, recorded at various depths in the parietal lobe and in ponto-mesencephalic areas, was investigated by laser-Doppler flowmetry in normotensive rabbits. These areas were chosen as representative of the vascular beds supplied by the carotid and vertebro-basilar systems, which exhibit different degrees of sympathetic innervation, the former being richer than the latter. Sympathetic stimulation at 30 imp/s affects cerebral blood flow in 77% of the parietal lobe and in 43% of the ponto-mesencephalic tested areas. In both cases the predominant effect was a reduction in blood flow (14.7 +/- 5.1% and 4.1 +/- 2.4%, respectively). The extent of the reduction in both areas was less if the stimulation frequency was decreased. Sometimes mean cerebral blood flow showed a small and transient increase, mainly in response to low-frequency stimulation. The morphology was analysed of low-frequency spontaneous oscillations in cerebral blood flow, attributed to vasomotion. Present in 41% of the tested areas (frequency 4-12 cycles/min, peak-to-peak amplitude 10-40% of mean value), these waves decreased in amplitude and increased in frequency during sympathetic stimulation, irrespective of changes in mean flow. The possibility has been proposed that the sympathetic action on low-frequency spontaneous oscillations may contribute to the protective influence that this system is known to exert on the blood-brain barrier in hypertension.

  18. Characterization of Cerebral Damage in a Monkey Model of Alzheimer's Disease Induced by Intracerebroventricular Injection of Streptozotocin.

    PubMed

    Yeo, Hyeon-Gu; Lee, Youngjeon; Jeon, Chang-Yeop; Jeong, Kang-Jin; Jin, Yeung Bae; Kang, Philyong; Kim, Sun-Uk; Kim, Ji-Su; Huh, Jae-Won; Kim, Young-Hyun; Sim, Bo-Woong; Song, Bong-Seok; Park, Young-Ho; Hong, Yonggeun; Lee, Sang-Rae; Chang, Kyu-Tae

    2015-01-01

    In line with recent findings showing Alzheimer's disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-human primate models are very limited. In this study, we aimed to characterize the cerebral damage caused by icv-STZ in non-human primates; to achieve this, three cynomolgus monkeys (Macaca fascicularis) were administered four dosages of STZ (2 mg/kg) dissolved in artificial cerebrospinal fluid and another three controls were injected with only artificial cerebrospinal fluid at the cerebellomedullary cistern. In vivo neuroimaging was performed with clinical 3.0 T MRI, followed by quantitative analysis with FSL for evaluation of structural changes of the brain. Immunohistochemistry was performed to evaluate cerebral histopathology. We showed that icv-STZ caused severe ventricular enlargement and parenchymal atrophy, accompanying amyloid-β deposition, hippocampal cell loss, tauopathy, ependymal cell loss, astrogliosis, and microglial activation, which are observed in human aged or AD brain. The findings suggest that the icv-STZ monkey model would be a valuable resource to study the mechanisms and consequences of a variety of cerebral pathologies including major pathological hallmarks of AD. Furthermore, the study of icv-STZ monkeys could contribute to the development of treatments for age- or AD-associated cerebral changes.

  19. The Comparisons of Cerebral Hemodynamics Induced by Obstructive Sleep Apnea with Arousal and Periodic Limb Movement with Arousal: A Pilot NIRS Study

    PubMed Central

    Zhang, Zhongxing; Schneider, Maja; Laures, Marco; Qi, Ming; Khatami, Ramin

    2016-01-01

    Obstructive sleep apnea syndrome (OSA) and restless legs syndrome (RLS) with periodic limb movement during sleep (PLMS) are two sleep disorders characterized by repetitive respiratory or movement events associated with cortical arousals. We compared the cerebral hemodynamic changes linked to periodic apneas/hypopneas with arousals (AHA) in four OSA-patients with periodic limb movements (PLMA) with arousals in four patients with RLS-PLMS using near-infrared spectroscopy (NIRS). AHA induced homogenous pattern of periodic fluctuations in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin, i.e., the decrease of HbO2 was accompanied by an increase of HHb during the respiratory event and resolved to reverse pattern when cortical arousal started. Blood volume (BV) showed the same pattern as HHb but with relative smaller amplitude in most of the AHA events.These changing patterns were significant as Wilcoxon signed-rank tests gave p < 0.001 when comparing the area under the curve of these hemodynamic parameters to zero. By contrast, in PLMA limb movements induced periodic increments in HbO2 and BV (Wilcoxon signed-rank tests, p < 0.001), but HHb changed more heterogeneously even during the events coming from the same patient. Heart rate (HR) also showed different patterns between AHA and PLMA. It significantly decreased during the respiratory event (Wilcoxon signed-rank test, p < 0.001) and then increased after the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001); while in PLMA HR first increased preceding the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001) and then decreased. The results of this preliminary study show that both AHA and PLMA induce changes in cerebral hemodynamics. The occurrence of cortical arousal is accompanied by increased HR in both events, but by different BV changes (i.e., decreased/increased BV in AHA/PLMA, respectively). HR changes may partially account for the increased cerebral hemodynamics during PLMA

  20. Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression.

    PubMed

    Zhai, Xiao; Chen, Xiao; Shi, Jiazi; Shi, Duo; Ye, Zhouheng; Liu, Wenwu; Li, Ming; Wang, Qijin; Kang, Zhimin; Bi, Hongda; Sun, Xuejun

    2013-12-01

    Molecular hydrogen has been proven effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce a considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced in Sprague-Dawley rats through middle cerebral artery occlusion. Intragastric administration of lactulose substantially increased breath hydrogen concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in the lactulose administration group won higher neurological scores and showed shorter escape latency time in the Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine concentration and increased superoxide dismutase activity. The effects of lactulose were superior to those of edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2 (Nrf2) in the brain as verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose by reducing hydrogen production. Our study for the first time demonstrates a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.

  1. Cerebral Paragonimiasis.

    PubMed

    Miyazaki, I

    1975-01-01

    The first case of cerebral paragonimiasis was reported by Otani in Japan in 1887. This was nine years after Kerbert's discovery of the fluke in the lungs of Bengal tigers and seven years after a human pulmonary infection by the fluke was demonstrated by Baelz and Manson. The first case was a 26-year-old man who had been suffering from cough and hemosputum for one year. The patient developed convulsive seizures with subsequent coma and died. The postmortem examination showed cystic lesions in the right frontal and occipital lobes. An adult fluke was found in the occipital lesion and another was seen in a gross specimen of normal brain tissue around the affected occipital lobe. Two years after Otani's discovery, at autopsy a 29-year-old man with a history of Jacksonian seizure was reported as having cerebral paragonimiasis. Some time later, however, it was confirmed that the case was actually cerebral schistosomiasis japonica. Subsequently, cases of cerebral paragonimiasis were reported. However, the majority of these cases were not confirmed histologically. It was pointed out that some of these early cases were probably not Paragonimus infection. After World War II, reviews as well as case reports were published. Recently, investigations have been reported from Korea, with a clinicla study on 62 cases of cerebral paragonimiasis seen at the Neurology Department of the National Medical Center, Seoul, between 1958 and 1964. In 1971 Higashi described a statistical study on 105 cases of cerebral paragonimiasis that had been treated surgically in Japan.

  2. MicroRNA-25 Negatively Regulates Cerebral Ischemia/Reperfusion Injury-Induced Cell Apoptosis Through Fas/FasL Pathway.

    PubMed

    Zhang, Jun-Feng; Shi, Li-Li; Zhang, Li; Zhao, Zhao-Hua; Liang, Fei; Xu, Xi; Zhao, Ling-Yu; Yang, Peng-Bo; Zhang, Jian-Shui; Tian, Ying-Fang

    2016-04-01

    MicroRNA-25 (miR-25) has been reported to be a major miRNA marker in neural cells and is strongly expressed in ischemic brain tissues. However, the precise mechanism and effect of miR-25 in cerebral ischemia/reperfusion (I/R) injury needs further investigations. In the present study, the oxygen-glucose deprivation (OGD) model was constructed in human SH-SY5Y and IMR-32 cells to mimic I/R injury and to evaluate the role of miR-25 in regulating OGD/reperfusion (OGDR)-induced cell apoptosis. We found that miR-25 was downregulated in the OGDR model. Overexpression of miR-25 via miRNA-mimics transfection remarkably inhibited OGDR-induced cell apoptosis. Moreover, Fas was predicted as a target gene of miR-25 through bioinformatic analysis. The interaction between miR-25 and 3'-untranslated region (UTR) of Fas mRNA was confirmed by dual-luciferase reporter assay. Fas protein expression was downregulated by miR-25 overexpression in OGDR model. Subsequently, the small interfering RNA (siRNA)-mediated knockdown of Fas expression also inhibited cell apoptosis induced by OGDR model; in contrast, Fas overexpression abrogated the protective effects of miR-25 on OGDR-induced cells. Taken together, our results indicate that the upregulation of miR-25 inhibits cerebral I/R injury-induced apoptosis through downregulating Fas/FasL, which will provide a promising therapeutic target.

  3. CoCl2-induced biochemical hypoxia down regulates activities and expression of super oxide dismutase and catalase in cerebral cortex of mice.

    PubMed

    Rani, Anupama; Prasad, S

    2014-09-01

    Hypoxia-induced oxidative stress is one of the major hallmark reasons underlying brain dysfunction. In the present manuscript, we have used CoCl2-induced hypoxic mice to investigate alterations in the activities of chief antioxidative stress enzymes- superoxide dismutase (SOD) and catalase (CAT) and expression of their genes Sod1 and Cat in the cerebral cortex as this model has not been routinely used for carrying out such study. Hypoxia mimetic mice model was accordingly developed by oral CoCl2 administration to mice and validated by analyzing alterations in the expression of the hypoxia inducible factor gene Hif-1α and its immediate responsive genes. Our Western blot data demonstrated that a dose of 40 mg/kg BW of CoCl2 was able to generate hypoxia like condition in mice in which Hif-1α and its immediate responsive genes-glutamate transporter-1 (Slc2a1) and erythropoietin (Epo) expression were up regulated. Our in-gel assay data indicated that SOD and CAT activities significantly declined and it was associated with significant down regulation of Sod1 and Epo expression as evident from our semi quantitative RT-PCR and Western blot data, which might be correlated with up regulation of Hif-1α expression in the cerebral cortex of the CoCl2-treated hypoxic mice. Our findings suggest that CoCl2-induced hypoxic mouse model is useful for studying alterations in the anti oxidative enzymes and biochemical/molecular/neurobiological analysis of hypoxia-induced alterations in brain function.

  4. The Degree of Lipiodol Accumulation Can Be an Indicator of Successful Treatment for Unresectable Hepatocellular Carcinoma (HCC) Patients - in the Case of Transcatheter Arterial Chemoembolization (TACE) and External Beam Radiotherapy (EBRT)

    PubMed Central

    Yang, Ping; Zeng, Zhao-Chong; Wang, Bin-Liang; Zhang, Jian-Ying; Fan, Jia; Zhou, Jian; Hu, Yong

    2016-01-01

    Purpose: Transcatheter arterial chemoembolization (TACE) in combination with external beam radiotherapy (EBRT) results in improved survival due to better local control in patients with unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate lipiodol accumulation, as it reflects tumor burden and is a potential prognostic factor, in HCC patients treated with TACE/EBRT. Methods and Materials: We retrospectively studied 147 patients with unresectable HCC treated with TACE and EBRT. Clinical features, adverse reactions, and prognostic factors were analyzed. All patients were treated with TACE 1-6 times in combination with EBRT (44-66 Gy) in dose of 2 Gy/fraction given once a day five times a week. Tumor status and laboratory findings were followed. The degree of lipiodol accumulation was assessed by computed tomography before EBRT, and was categorized as either complete/intense or low/moderate. Results: The response rate of tumor size after EBRT was 68.2%, median survival was 23.1 months, and overall survival rates were 86.6%, 49.2%, and 28.2% at 1, 2, and 3 years, respectively. Univariate analysis showed that lower hemoglobin levels, higher alkaline phosphatase levels, Child-Pugh B, negative alpha-fetoprotein (AFP) response after EBRT, poor treatment response after EBRT, tumor diameter >10 cm, and poor lipiodol accumulation were unfavorable prognostic factors. On multivariate analysis, higher hemoglobin levels, Child-Pugh A, decreased AFP levels after treatment, Helical Tomotherapy (HT) and intense lipiodol accumulation after TACE were significant favorable predictors. Conclusions: The degree of lipiodol accumulation before EBRT is a prognostic factor in patients with unresectable HCC. Increased AFP levels after EBRT are always associated with poor survival. HT is recommended as a potentially better EBRT modality than three-dimensional conformal radiation therapy (3D-CRT). PMID:27471557

  5. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

    PubMed

    Kokubu, Yasuhiro; Yamaguchi, Tomoko; Kawabata, Kenji

    2017-04-29

    Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study. In the recent study, an induction method of BMECs from PSCs has been established, making it possible to more precisely study the in vitro human BBB function. Here, using induced pluripotent stem (iPS) cell-derived BMECs, we examined the effects of oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) on BBB permeability. OGD disrupted the barrier function, and the dysfunction was rapidly restored by re-supply of the oxygen and glucose. Interestingly, TNF-α, which is known to be secreted from astrocytes and microglia in the cerebral ischemia, prevented the restoration of OGD-induced barrier dysfunction in an apoptosis-independent manner. Thus, we could establish the in vitro BBB disease model that mimics the cerebral ischemia by using iPS cell-derived BMECs.

  6. The effect of long-term supplementation of vitamin C on leukocyte adhesion to the cerebral endothelium in STZ-induced diabetic rats.

    PubMed

    Jariyapongskul, Amporn; Patumraj, Suthiluk; Yamaguchi, Saburo; Niimi, Hideyuki

    2002-01-01

    The effect of long-term supplementation of vitamin C on leukocyte adhesion to the cerebral endothelium was investigated in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar Furth rats by intravenous injection of STZ. The vitamin C, ascorbic acid, was supplemented with drinking water (1 g/l). The rats were divided into control and diabetic groups without or with supplementation of vitamin C. The cerebral microcirculation was directly observed through a cranial window after different periods (12, 24 and 36 weeks) of vitamin C supplementation, using fluorescence videomicroscopy. Leukocyte adhesion to the venular endothelium was examined by labeling leukocytes with rhodamin 6G. The number density of adherent leukocytes in STZ-diabetic rats was increased significantly, compared with control rats. This increase in leukocyte adhesion was prevented by the long-term supplemented vitamin C. It was suggested that the antioxidant effect of vitamin C might be responsible for the prevention of leukocyte adhesion in diabetes mellitus.

  7. Hyperthermia-induced seizures alter adenosine A1 and A2A receptors and 5'-nucleotidase activity in rat cerebral cortex.

    PubMed

    León-Navarro, David Agustín; Albasanz, José L; Martín, Mairena

    2015-08-01

    Febrile seizure is one of the most common convulsive disorders in children. The neuromodulator adenosine exerts anticonvulsant actions through binding adenosine receptors. Here, the impact of hyperthermia-induced seizures on adenosine A1 and A2A receptors and 5'-nucleotidase activity has been studied at different periods in the cerebral cortical area by using radioligand binding, real-time PCR, and 5'-nucleotidase activity assays. Hyperthermic seizures were induced in 13-day-old rats using a warmed air stream from a hair dryer. Neonates exhibited rearing and falling over associated with hindlimb clonus seizures (stage 5 on Racine scale criteria) after hyperthermic induction. A significant increase in A1 receptor density was observed using [(3) H]DPCPX as radioligand, and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density was detected, using [(3) H]ZM241385 as radioligand, 48 h after hyperthermia-evoked convulsions. These short-term changes in A1 and A2A receptors were also accompanied by a loss of 5'-nucleotidase activity. No significant variations either in A1 or A2A receptor density or 5'-nucleotidase were observed 5 and 20 days after hyperthermic seizures. Taken together, both regulation of A1 and A2A receptors and loss of 5'-nucleotidase in the cerebral cortex suggest the existence of a neuroprotective mechanism against seizures. Febrile seizure is one of the most common convulsive disorders in children. The consequences of hyperthermia-induced seizures (animal model of febrile seizures) on adenosine A1 and A2A receptors and 5'-nucleotidase activity have been studied at different periods in cerebral cortical area. A significant increase in A1 receptor density and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density and 5'-nucleotidase activity was detected 48 h after convulsions evoked by hyperthermia

  8. Cerebral Palsy (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Cerebral Palsy KidsHealth > For Parents > Cerebral Palsy A A A ... kids who are living with the condition. About Cerebral Palsy Cerebral palsy is one of the most common ...

  9. Cerebral palsy - resources

    MedlinePlus

    Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/cerebral_palsy/cerebral_palsy. ...

  10. The ameliorative effects of exercise on cognitive impairment and white matter injury from blood-brain barrier disruption induced by chronic cerebral hypoperfusion in adolescent rats.

    PubMed

    Lee, Jae-Min; Park, Jong-Min; Song, Min Kyung; Oh, Yoo Joung; Kim, Chang-Ju; Kim, Youn-Jung

    2017-01-18

    Vascular dementia is the progressive change in blood vessels that leads to neuronal injuries in vulnerable areas induced by chronic cerebral hypoperfusion (CCH). CCH induces disruption of blood-brain barrier (BBB), and this BBB disruption can initiate the cognitive impairment and white matter injury. In the present study, we evaluated the effect of treadmill exercise on the cognitive impairment, white matter injury, and BBB disruption induced by CCH. Vascular dementia was induced by permanent bilateral common carotid arteries occlusion (BCCAO) in rats. The rats in the exercise group were made to run on a treadmill for 30min once a day for 14 weeks, starting 4 weeks after birth. Our results revealed that treadmill exercise group was alleviated the cognitive impairment and myelin degradation induced by CCH. The disruption of BBB after CCH indicates degradation of occludin, zonula occluden-1 (ZO-1), and up-regulation of matrix metalloproteinases (MMPs). Treadmill exercise may provide protective effects on BBB disruption from degradation of occludin, ZO-1, and overexpression of MMP-9 after CCH. These findings suggest that treadmill exercise ameliorates cognitive impairment and white matter injury from BBB disruption induced by CCH in rats. The present study will be valuable for means of prophylactic and therapeutic intervention for patients with CCH.

  11. Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.

    PubMed

    Hoiland, Ryan L; Bain, Anthony R; Tymko, Michael M; Rieger, Mathew G; Howe, Connor A; Willie, Christopher K; Hansen, Alex B; Flück, Daniela; Wildfong, Kevin W; Stembridge, Mike; Subedi, Prajan; Anholm, James; Ainslie, Philip N

    2017-04-01

    Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% [Formula: see text]). Ventilation, [Formula: see text] and [Formula: see text], blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (P < 0.01), a finding explained by a lower [Formula: see text] (P < 0.01). Upon mathematical correction for [Formula: see text], the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of [Formula: see text] At high altitude, theophylline (n = 6) had no effect on CBF compared with placebo (n = 6) when end-tidal gases were comparable (P > 0.05). We conclude that adenosine receptor-dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans.NEW & NOTEWORTHY The signaling pathways that regulate human cerebral blood flow in hypoxia remain poorly understood. Using a randomized, double-blinded, and placebo-controlled study design, we determined that adenosine receptor-dependent signaling is not obligatory for the

  12. Sesamin attenuates behavioral, biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats.

    PubMed

    Khan, Mohd Moshahid; Ishrat, Tauheed; Ahmad, Ajmal; Hoda, Md Nasrul; Khan, M Badruzzaman; Khuwaja, Gulrana; Srivastava, Pallavi; Raza, Syed Shadab; Islam, Fakhrul; Ahmad, Saif

    2010-01-05

    Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species (ROS) with consequent reperfusion injury. ROS cause lipid peroxidation, protein oxidation, and DNA damage, all of which are deleterious to cells. So diminishing the production of free radicals and scavenging them may be a successful therapeutic strategy for the protection of brain tissue in cerebral stroke. The present study investigated the neuroprotective effect of sesamin (Sn) to reduce brain injury after middle cerebral artery occlusion (MCAO). The middle cerebral artery (MCA) of adult male Wistar rat was occluded for 2h and reperfused for 22h. Sesamin is the most abundant lignan in sesame seed oil is a potent antioxidant. Sesamin (30 mg/kg) was given orally twice, 30 min before the onset of ischemia and 12h after reperfusion. The initial investigations revealed that sesamin reduced the neurological deficits in terms of behavior and reduced the level of thiobarbituric acid reactive species (TBARS), and protein carbonyl (PC) in the different areas of the brain when compared with the MCAO group. A significantly depleted level of glutathione and its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) in MCAO group were protected significantly in MCAO group treated with sesamin. The present study suggests that sesamin may be able to attenuate the ischemic cell death and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the rat brain. Thus, sesamin may be a potential compound in stroke therapy.

  13. Time course of cerebral hypoperfusion-induced neurodegenerative changes in the cortex of male and female rats.

    PubMed

    Stanojlović, M; Horvat, A; Guševac, I; Grković, I; Mitrović, N; Buzadžić, I; Drakulić, D

    2014-01-01

    To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups - controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated downregulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.

  14. Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils.

    PubMed

    Dekanski, Dragana; Selaković, Vesna; Piperski, Vesna; Radulović, Zeljka; Korenić, Andrej; Radenović, Lidija

    2011-10-15

    The beneficial effects of antioxidant nutrients, as well as complex plant extracts, in cerebral ischemia/reperfusion brain injury are well known. Mediterranean diet, rich in olive products, is associated with lower incidence of cardiovascular disease, cancer, inflammation and stroke. In this study, the possible neuroprotective effect of standardized dry olive leaf extract (OLE) is investigated for the first time. Transient global cerebral ischemia in Mongolian gerbils was used to investigate the OLE effects on different parameters of oxidative stress and neuronal damage in hippocampus. The biochemical measurements took place at different time points (80min, 2, 4 and 24h) after reperfusion. The effects of applied OLE were compared with effects of quercetin, a known neuroprotective plant flavonoid. Pretreatment with OLE (100mg/kg, per os) significantly inhibited production of superoxide and nitric oxide, decreased lipid peroxidation, and increased superoxide dismutase activity in all time points examined. Furthermore, OLE offered histological improvement as seen by decreasing neuronal damage in CA1 region of hippocampus. The effects of applied OLE were significantly higher than effects of quercetin (100mg/kg, per os). Our results indicate that OLE exerts a potent neuroprotective activity against neuronal damage in hippocampus after transient global cerebral ischemia, which could be attributed to its antioxidative properties.

  15. Cerebral palsy.

    PubMed

    Colver, Allan; Fairhurst, Charles; Pharoah, Peter O D

    2014-04-05

    The syndrome of cerebral palsy encompasses a large group of childhood movement and posture disorders. Severity, patterns of motor involvement, and associated impairments such as those of communication, intellectual ability, and epilepsy vary widely. Overall prevalence has remained stable in the past 40 years at 2-3·5 cases per 1000 livebirths, despite changes in antenatal and perinatal care. The few studies available from developing countries suggest prevalence of comparable magnitude. Cerebral palsy is a lifelong disorder; approaches to intervention, whether at an individual or environmental level, should recognise that quality of life and social participation throughout life are what individuals with cerebral palsy seek, not improved physical function for its own sake. In the past few years, the cerebral palsy community has learned that the evidence of benefit for the numerous drugs, surgery, and therapies used over previous decades is weak. Improved understanding of the role of multiple gestation in pathogenesis, of gene environment interaction, and how to influence brain plasticity could yield significant advances in treatment of the disorder. Reduction in the prevalence of post-neonatal cerebral palsy, especially in developing countries, should be possible through improved nutrition, infection control, and accident prevention.

  16. Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia.

    PubMed

    Kim, Dong Won; Lee, Jae-Chul; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Seo, Jeong Yeol; Cho, Jun Hwi; Kang, Il Jun; Hong, Seongkweon; Kim, Young-Myeong; Won, Moo-Ho; Kim, In Hye

    2015-09-01

    Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia could reduce neuronal damage/death following a subsequent lethal transient cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2 and tumor necrosis factor (TNF)-α as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between animals with lethal ischemia and ones with IPC followed by lethal ischemia. In the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however, IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions of all cytokines were significantly decreased in the SP after lethal ischemia and hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4 and IL-13) in the stratum pyramidale of the CA1 region following no lethal ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC were continuously maintained is the SP of the CA1 region after lethal ischemia. However, pro-inflammatory cytokines (IL-2 and TNF-α) in the SP of the CA1 region were similar those in the sham-operated animals with IPC, and the IL-4 and IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion, this study shows that anti-inflammatory cytokines significantly increased and longer maintained by IPC and this might be closely associated with neuroprotection after lethal transient cerebral ischemia.

  17. Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex.

    PubMed

    Alonso, David; Serrano, Julia; Rodríguez, Ignacio; Ruíz-Cabello, Jesús; Fernández, Ana Patricia; Encinas, Juan Manuel; Castro-Blanco, Susana; Bentura, María Luisa; Santacana, María; Richart, Ana; Fernández-Vizarra, Paula; Uttenthal, Lars Otto; Rodrigo, José

    2002-02-04

    Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS-immunoreactive band and calcium-dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV-V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium-independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham-perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L-NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia-reperfusion contributes to cerebral injury.

  18. Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

    PubMed

    Zheng, Li; Ding, Junli; Wang, Jianwei; Zhou, Changman; Zhang, Weiguang

    2016-02-01

    Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with S-methylisothiourea sulfate (SMT), a high-selective inhibitor of iNOS. Seventy-two male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) + vehicle, and MCAO + SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5-triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post-reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia-reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase-3-positive), and increased phospho (p)-AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia-reperfusion injury by inhibiting neuronal apoptosis via maintaining p-AKT activity.

  19. Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats.

    PubMed

    Kumar, Peeyush T; Antony, Sherin; Nandhu, Mohan S; Sadanandan, Jayanarayanan; Naijil, George; Paulose, Chiramadathikudiyil S

    2011-05-01

    Nutritional therapy is a challenging but necessary dimension in the management of diabetes and neurodegenerative changes associated with it. The study evaluates the effect of vitamin D(3) in preventing the altered function of cholinergic, insulin receptors and GLUT3 in the cerebral cortex of diabetic rats. Muscarinic M3 acetylcholine receptors in pancreas control insulin secretion. Vitamin D(3) treatment in M3 receptor regulation in the pancreatic islets was also studied. Radioreceptor binding assays and gene expression was done in the cerebral cortex of male Wistar rats. Immunocytochemistry of muscarinic M3 receptor was studied in the pancreatic islets using specific antibodies. Y-maze was used to evaluate the exploratory and spatial memory. Diabetes induced a decrease in muscarinic M1, insulin and vitamin D receptor expression and an increase in muscarinic M3, α7 nicotinic acetylcholine receptor, acetylcholine esterase and GLUT3 expression. Vitamin D(3) and insulin treatment reversed diabetes-induced alterations to near control. Diabetic rats showed a decreased Y-maze performance while vitamin D(3) supplementation improved the behavioural deficit. In conclusion, vitamin D(3) shows a potential therapeutic effect in normalizing diabetes-induced alterations in cholinergic, insulin and vitamin D receptor and maintains a normal glucose transport and utilisation in the cortex. In addition vitamin D(3) modulated muscarinic M3 receptors activity in pancreas and plays a pivotal role in controlling insulin secretion. Hence our findings proved, vitamin D(3) supplementation as a potential nutritional therapy in ameliorating diabetes mediated cortical dysfunctions and suggest an interaction between vitamin D(3) and muscarinic M3 receptors in regulating insulin secretion from pancreas.

  20. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.

    PubMed

    Paredes, Sergio D; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A F

    2015-01-01

    Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

  1. Transient middle cerebral artery occlusion and reperfusion alters inducible NOS expression within the ventrolateral medulla and modulates cardiovascular function during static exercise.

    PubMed

    Ally, Ahmmed; Maher, Timothy J

    2011-09-01

    A major cause of stroke is cerebral ischemia in regions supplied by the middle cerebral artery (MCA). In this study, we hypothesized that compromised cardiovascular function during static exercise may involve altered expression of inducible NOS (iNOS) protein within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). We compared cardiovascular responses and iNOS protein expression within the left and right sides of both RVLM and CVLM in sham-operated rats and in rats with a 90 min left-sided MCA occlusion (MCAO) followed by 24 h of reperfusion. Increases in blood pressure during a static muscle contraction were attenuated in MCAO rats compared with sham-operated rats. Also, iNOS expression within the left RVLM was augmented compared with the right RVLM in MCAO rats and compared with both RVLM quadrants in sham-operated rats. In contrast, compared with sham-operated rats and the right CVLM of MCAO rats, iNOS expression was attenuated in the left CVLM in left-sided MCAO rats. These data suggest that the attenuation of pressor responses during static exercise in MCAO rats involves overexpression of iNOS within the ipsilateral RVLM and attenuation in iNOS within the ipsilateral CVLM. Differential expression of iNOS within the medulla plays a role in mediating cardiovascular responses during static exercise following stroke.

  2. Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress: possible involvement of oxygen free radicals.

    PubMed

    Bates, Brian; Hirt, Lorenz; Thomas, Sunu S; Akbarian, Schahram; Le, Dean; Amin-Hanjani, Sepideh; Whalen, Michael; Jaenisch, Rudolf; Moskowitz, Michael A

    2002-02-01

    To explore the role of neurotrophin-3 (NT-3) during cerebral ischemia, NT-3-deficient brains were subjected to transient focal ischemia. Conditional mutant brains produced undetectable amounts of NT-3 mRNA, whereas the expression of the neurotrophin, BDNF, the NT-3 receptor, TrkC, and the nonselective, low-affinity neurotrophin receptor p75NTR, were comparable to wild-type. Baseline absolute blood flow, vascular and neuroanatomical features, as well as physiological measurements were also indistinguishable from wild-type. Interestingly, the absence of NT-3 led to a significantly decreased infarct volume 23 h after middle cerebral artery occlusion. Consistent with this, the addition of NT-3 to primary cortical cell cultures exacerbated neuronal death caused by oxygen-glucose deprivation. Coincubation with the oxygen free radical chelator, trolox, diminished potentiation of neuronal death. NT-3 also enhanced neuronal cell death and the production of reactive oxygen species caused by oxidative damage inducing agents. We conclude that endogenous NT-3 enhanced neuronal injury during acute stroke, possible by increasing oxygen-radical mediated cell death.

  3. Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area in rats.

    PubMed

    Luo, Pan; Zhang, Xiaoxue; Lu, Yun; Chen, Cheng; Li, Changjun; Zhou, Mei; Lu, Qing; Xu, Xulin; Shen, Guanxin; Guo, Lianjun

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Two weeks later, rats were treated with 30 mg/kg fluoxetine (intragastric injection, i.g.) for 6 weeks. Cognitive function was evaluated by Morris water maze (MWM) and novel objects recognition (NOR) test. Long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Western blotting was used to quantify the protein levels. Our results showed that fluoxetine treatment significantly improved the cognitive impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, 2VO caused an up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) surface expressions in the hippocampal CA1 area and fluoxetine also effectively recovered the disorder of HCN2 surface expressions, which may be a possible mechanism that fluoxetine treatment ameliorates cognitive impairments in rats with CCH.

  4. Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats.

    PubMed

    Sahin, S; Alkan, T; Temel, S G; Tureyen, K; Tolunay, S; Korfali, E

    2010-02-01

    The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83; p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/-0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group 3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/-0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.

  5. Modified Constraint-Induced Movement Therapy Combined with Bimanual Training (mCIMT-BiT) in Children with Unilateral Spastic Cerebral Palsy: How Are Improvements in Arm-Hand Use Established?

    ERIC Educational Resources Information Center

    Aarts, Pauline B.; Jongerius, Peter H.; Geerdink, Yvonne A.; van Limbeek, Jacques; Geurts, Alexander C.

    2011-01-01

    A recent randomized controlled trial indicated that modified Constraint-Induced Movement Therapy followed by Bimanual Training (mCIMT-BiT) is an effective intervention to improve spontaneous use of the affected upper limb in children with unilateral spastic cerebral palsy (CP). The present study aimed to investigate how the above-mentioned…

  6. Cerebral embolic stroke after disappearing takotsubo cardiomyopathy.

    PubMed

    Matsuzono, Kosuke; Ikeda, Yoshio; Deguchi, Shoko; Yamashita, Toru; Kurata, Tomoko; Deguchi, Kentaro; Abe, Koji

    2013-11-01

    Takotsubo cardiomyopathy can induce cerebral embolic stroke because of intracardiac thrombosis, but the timing of cardiogenic embolism relating to takotsubo cardiomyopathy has not been well described. We evaluated a 71-year-old woman with takotsubo cardiomyopathy, who developed cardiogenic cerebral embolism after recovery of cardiac wall motion. Nevertheless, we treated her with anticoagulation therapy. The present clinical observation suggests that attention should be paid to the timing when takotsubo cardiomyopathy resolves against risk of cardiogenic cerebral embolism.

  7. Cerebral Malaria.

    PubMed

    Marsden, P D; Bruce-Chwatt, L J

    1975-01-01

    Cerebral malaria is an acute diffuse encephalopathy associated only with Plasmodium falciparum. It is probably a consequence of the rapid proliferation of the parasites in the body of man in relation to red cell invasion, and results in stagnation of blood flow in cerebralcapillaries with thromobotic occlusion of large numbers of cerebral capillaries. The subsequent cerebral pathology is cerebral infarction with haemorrhage and cerebral oedema. The wide prevalence of P. falciparum in highly endemic areas results in daily challenges to patients from several infected mosquitoes. It is thus important to understand the characteristics of P. falciparum, since this is one of the most important protozoan parasites of man and severe infection from it constitutes one of the few real clinical emergencies in tropical medicine. One of the more important aspects of the practice of medicine in the tropics is to establish a good understanding of the pattern of medical practice in that area. This applies to malaria as well as to other diseases. The neophyte might be somewhat surprised to learn, for example that an experienced colleague who lives in a holoendemic malarious area such as West Africa, sees no cerebral malaria. But the explanation is simple when the doctor concerned has a practice which involves treating adults only. Cerebral malaria is rare in adults, because in highly endemic areas, by the age of 1 year most of the infants in a group under study have already experienced their first falciparum infection. By the time they reach adult life, they have a solid immunity against severe falciparum infections. In fact, "clinical malaria" could occur in such a group under only two circumstances: 1) in pregnancy, a patent infection with P. falciparum might develop, probably due to an IgG drain across the placenta to the foetus;2) in an individual who has constantly taken antimalarials and who may have an immunity at such a low level that when antimalarial therapy is interrupted

  8. Resting State and Diffusion Neuroimaging Predictors of Clinical Improvements Following Constraint-Induced Movement Therapy in Children With Hemiplegic Cerebral Palsy.

    PubMed

    Manning, Kathryn Y; Fehlings, Darcy; Mesterman, Ronit; Gorter, Jan Willem; Switzer, Lauren; Campbell, Craig; Menon, Ravi S

    2015-10-01

    The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = -0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy.

  9. Effects of Buprenorphine and Meloxicam Analgesia on Induced Cerebral Ischemia in C57BL/6 Male Mice

    PubMed Central

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas SP

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice. PMID:23582417

  10. Neuroprotection by Methylene Blue in Cerebral Global Ischemic Injury Induced Blood-Brain Barrier Disruption and Brain Pathology: A Review.

    PubMed

    Wiklund, Lars; Sharma, Aruna; Sharma, Hari Shanker

    2016-01-01

    Transient global ischemic cerebral injury is a consequence of cardiac arrest and accounts for approximately 450,000 annual deaths with a mortality of approximately 90%. Serious morbidity follows for many of the survivors and up to 16% of patients achieving restoration of spontaneous circulation develop brain death. Other survivors are left with persistent cognitive impairment such as memory and sensimotor deficits, reducing quality of life and resulting in heavy costs on society. Many studies over the years have been devoted to improving outcome after cardiac arrest and have, to a certain degree succeeded, especially locally in areas where improvement of ambulance organizations have been effective. In spite of this serious problems remain and the chances of cerebral survival need to increase if over-all results, i.e. survival as well as cognitive function, are to improve. Methylene blue, a textile dye synthesized in the late 19th century has also been used in medicine for different purposes. One of its effects is to increase systemic blood pressure, but other effects have been documented, among which are its neuroprotective effects well-noted during the last few years. In this review we have appraised these findings in relation to global ischemic injury.

  11. A novel embolic middle cerebral artery occlusion model induced by thrombus formed in common carotid artery in rat.

    PubMed

    Ma, Yin-Zhong; Li, Li; Song, Jun-Ke; Niu, Zi-Ran; Liu, Hai-Feng; Zhou, Xiang-Shan; Xie, Fu-Sheng; Du, Guan-Hua

    2015-12-15

    Stroke is a major cause of death and disability worldwide. However, treatment options to date are very limited. To meet the need for validating the novel therapeutic approaches and understanding the physiopathology of the ischemic brain injury, experimental stroke models were critical for preclinical research. However, commonly used embolic stroke models are reluctant to mimic the clinical situation and not suitable for thrombolytic timing studies. In this paper, we established a standard method for producing a rat embolic stroke model with autologous thrombus formed within the common carotid artery (CCA) by constant galvanic stimulation. Then the thrombus was shattered and channeled into the origin of the MCA and small (lacunar) artery. To identify the success of MCA occlusion, regional cerebral blood flow was monitored, neurological deficits and infarct volumes were measured at 2, 4 and 6h postischemia. This model developed a predictable infarct volume (38.37 ± 2.88%) and gradually reduced blood flow (20% of preischemic baselines) within the middle cerebral artery (MCA) territory. The thrombus occluded in the MCA was able to be lysed by a tissue-type plasminogen activator (t-PA) within 4h postischemia. The techniques presented in this paper would help investigators to overcome technical problems for stroke research.

  12. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    PubMed

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  13. GPER1/GPR30 activation improves neuronal survival following global cerebral ischemia induced by cardiac arrest in mice

    PubMed Central

    Kosaka, Y; Quillinan, N; Bond, CT; Traystman, RJ; Hurn, PD; Herson, PS

    2012-01-01

    Female sex steroids, particularly estrogens, contribute to the sexually dimorphic response observed in cerebral ischemic outcome, with females being relatively protected compared to males. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR), we previously demonstrated that estrogen neuroprotection is mediated in part by the estrogen receptor β, with no involvement of estrogen receptor α. In this study we examined the neuroprotective effect of the novel estrogen receptor, G-protein coupled estrogen receptor 1 (GPER1/GPR30). Male mice administered the GPR30 agonist G1 exhibited significantly reduced neuronal injury in the hippocampal CA1 region and striatum. The magnitude of neuroprotection observed in G1 treated mice was indistinguishable from estrogen treated mice, implicating GPR30 in estrogen neuroprotection. Real-time quantitative RT-PCR indicates that G1 treatment increases expression of the neuroprotective ion channel, small conductance calcium-activated potassium channel 2. We conclude that GPR30 agonists show promise in reducing brain injury following global cerebral ischemia. PMID:23483801

  14. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  15. Multiple brain abscesses from isolated cerebral mucormycosis.

    PubMed Central

    Escobar, A; Del Brutto, O H

    1990-01-01

    A report is presented of a patient with cerebral mucormycosis without rhinosinusal or systemic evidence of the disease. The predisposing condition was drug-induced immunosuppression. Computed tomography (CT) showed focal areas of abnormal enhancement which correlated with necropsy findings of localised parenchymal brain damage; this represented encapsulated brain abscesses, a rare form of presentation of cerebral mucormycosis. Images PMID:2351973

  16. Inhibition of central angiotensin converting enzyme ameliorates scopolamine induced memory impairment in mice: role of cholinergic neurotransmission, cerebral blood flow and brain energy metabolism.

    PubMed

    Tota, Santoshkumar; Nath, Chandishwar; Najmi, Abul Kalam; Shukla, Rakesh; Hanif, Kashif

    2012-06-15

    Evidences indicate that inhibition of central Renin angiotensin system (RAS) ameliorates memory impairment in animals and humans. Earlier we have reported involvement of central angiotensin converting enzyme (ACE) in streptozotocin induced neurodegeneration and memory impairment. The present study investigated the role of central ACE in cholinergic neurotransmission, brain energy metabolism and cerebral blood flow (CBF) in model of memory impairment induced by injection of scopolamine in mice. Perindopril (0.05 and 0.1 mg/kg, PO) was given orally for one week before administration of scopolamine (3mg/kg, IP). Then, memory function was evaluated by Morris water maze and passive avoidance tests. CBF was measured by laser Doppler flowmetry. Biochemical and molecular parameters were estimated after the completion of behavioral studies. Scopolamine caused impairment in memory which was associated with reduced CBF, acetylcholine (ACh) level and elevated acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level. Perindopril ameliorated scopolamine induced amnesia in both the behavioral paradigms. Further, perindopril prevented elevation of AChE and MDA level in mice brain. There was a significant increase in CBF and ACh level in perindopril treated mice. However, scopolamine had no significant effect on ATP level and mRNA expression of angiotensin receptors and ACE in cortex and hippocampus. But, perindopril significantly decreased ACE activity in brain without affecting its mRNA expression. The study clearly showed the interaction between ACE and cholinergic neurotransmission and beneficial effect of perindopril can be attributed to improvement in central cholinergic neurotransmission and CBF.

  17. Long-term neuroprotection with 2-iminobiotin, an inhibitor of neuronal and inducible nitric oxide synthase, after cerebral hypoxia-ischemia in neonatal rats.

    PubMed

    van den Tweel, Evelyn R W; van Bel, Frank; Kavelaars, Annemieke; Peeters-Scholte, Cacha M P C D; Haumann, Johan; Nijboer, Cora H A; Heijnen, Cobi J; Groenendaal, Floris

    2005-01-01

    The short- and long-term neuroprotective effects of 2-iminobiotin, a selective inhibitor of neuronal and inducible nitric oxide synthase, were studied in 12-day-old rats following hypoxia-ischemia. Hypoxia-ischemia was induced by occlusion of the right carotid artery followed by 90 minutes of hypoxia (FiO2 0.08). Immediately on reoxygenation, 12 and 24 hours later the rats were treated with vehicle or 2-iminobiotin at a dose of 5.5, 10, 30, or 60 mg/kg per day. Histologic analysis of brain damage was performed at 6 weeks after hypoxia-ischemia. To assess early changes of cerebral tissue, levels of HSP70, nitrotyrosine, and cytochrome c were determined 24 hours after reoxygenation. Significant neuroprotection was obtained using a dose of 30 mg/kg per day of 2-iminobiotin. Levels of HSP70 were increased in the ipsilateral hemisphere in both groups (P<0.05), but the increase was significantly (P<0.05) less in the rats receiving the optimal dose of 2-iminobiotin (30 mg/kg per day). Hypoxia-ischemia did not lead to increased levels of nitrotyrosine, nor did 2-iminobiotin influence levels of nitrotyrosine. In contrast, hypoxia-ischemia induced an increase in cytochrome c level that was prevented by 2-iminobiotin. In conclusion, 2-iminobiotin administered after hypoxia-ischemia provides long-term neuroprotection. This neuroprotection is obtained by mechanisms other than a reduction of nitrotyrosine formation in proteins.

  18. Effects of cinnamaldehyde on PGE2 release and TRPV4 expression in mouse cerebral microvascular endothelial cells induced by interleukin-1beta.

    PubMed

    Ma, Yue-Ying; Huo, Hai-Ru; Li, Cang-Hai; Zhao, Bao-Sheng; Li, Lan-Fang; Sui, Feng; Guo, Shu-Ying; Jiang, Ting-Liang

    2008-03-01

    Cinnamaldehyde is a principle compound isolated from Guizhi-Tang (GZT), which is a famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions. Transient receptor potential vanilloid subtype 4 (TRPV4) is expressed in the anterior hypothalamus and may act as thermosensor. The purpose of the present study was to investigate the effects of cinnamaldehyde on the production of prostaglandin E2 (PGE2) and the expression of TRPV4 in mouse cerebral microvascular endothelial cell strain (b.End3). In the research work, the b.End3 cells were cultured in DMEM medium containing interleukin-1beta (IL-1beta) in the presence or absence of ruthenium red (RR), a kind of known TRPV4 inhibitor, or different concentrations of cinnamaldehyde. The results suggested that IL-1beta significantly increase production of PGE2 and cinnamaldehyde evidently decrease IL-1beta-induced PGE2 production, while RR showed no inhibitory effect on PGE2 production. Moreover, it was identified that TRPV4 was expressed at the mRNA and protein levels in b.End3 cells. IL-1beta could up-regulate the expression of TRPV4, RR and cinnamaldehyde could down-regulate the high expression of mRNA and protein of TRPV4 by IL-1beta induced in b.End3 cells. In conclusion, cinnamaldehyde decreased the production of PGE2 and the expression of TRPV4 in b.End3 cells induced by IL-1beta.

  19. Pentylenetetrazol-induced seizures are associated with Na⁺,K⁺-ATPase activity decrease and alpha subunit phosphorylation state in the mice cerebral cortex.

    PubMed

    Marquezan, Bárbara P; Funck, Vinícius R; Oliveira, Clarissa V; Pereira, Letícia M; Araújo, Stífani M; Zarzecki, Micheli S; Royes, Luiz Fernando F; Furian, Ana Flávia; Oliveira, Mauro S

    2013-08-01

    The present study aimed to investigate whether Na(+),K(+)-ATPase activity and phosphorylation state of the catalytic α subunit are altered by pentylenetetrazol (PTZ)-induced seizures. PTZ (30, 45 or 60 g/kg, i.p.) was administered to adult male Swiss mice, and Na(+),K(+)-ATPase activity and phosphorylation state were measured in the cerebral cortex 15 min after PTZ administration. Na(+),K(+)-ATPase activity significantly decreased after PTZ-induced seizures (60 mg/kg). Immunoreactivity of phosphorylated Ser943 at α subunit was increased after PTZ-induced seizures. A significant positive correlation between Na(+),K(+)-ATPase activity and latency to myoclonic jerks and generalized seizures was found. Conversely, a strong negative correlation between Ser943 phosphorylation and latency to generalized seizures was detected. Given the role of Na(+),K(+)-ATPase as a major regulator of brain excitability, Ser943 at Na(+),K(+)-ATPase α subunit may represent a potentially valuable new target for drug development for seizure disorders.

  20. Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

    PubMed

    Kawai, S; Tani, M; Okamura, J; Ogawa, M; Ohashi, Y; Monden, M; Hayashi, S; Inoue, J; Kawarada, Y; Kusano, M; Kubo, Y; Kuroda, C; Sakata, Y; Shimamura, Y; Jinno, K; Takahashi, A; Takayasu, K; Tamura, K; Nagasue, N; Nakanishi, Y; Makino, M; Masuzawa, M; Yumoto, Y; Mori, T; Oda, T

    1997-04-01

    A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

  1. Cerebral malaria

    PubMed Central

    Newton, C.; Hien, T. T.; White, N.

    2000-01-01

    Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogenous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications—for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.

 PMID:10990500

  2. Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study.

    PubMed

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2008-03-01

    Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.

  3. Caffeine induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated-BOLD fMRI study

    PubMed Central

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2009-01-01

    Although functional MRI (fMRI) based on blood oxygenation-level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia calibrated-BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). In this study, we implemented a quantitative R2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated-BOLD method, to examine the CBF and CMRO2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200mg caffeine dose. A dual echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, ±11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, ±2.9) and CMRO2 (+20.7%, ±1.4), and caffeine decreased CBF (-34.5%, ±2.6) with a non-significant change in CMRO2 (+5.2%, ±6.4). The coupling between CBF and CMRO2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated-BOLD methodology using R2* is a promising approach for evaluating CBF and CMRO2 changes in response to pharmacological interventions. PMID:18191583

  4. Acute Multi-modal Neuroimaging in a Porcine Model of Endothelin-1-Induced Cerebral Ischemia: Defining the Acute Infarct Core.

    PubMed

    d'Esterre, Christopher D; Aviv, Richard I; Morrison, Laura; Fainardi, Enrico; Lee, Ting Yim

    2015-06-01

    In a porcine ischemic stroke model, we sought to compare the acute predicted infarct core volume (PIV) defined by CT perfusion (CTP)-hemodynamic parameters and MR-diffusion-weighted imaging (MR-DWI)/apparent diffusion coefficient (ADC), with the true infarct core volume (TIV) as defined by histology. Ten Duroc-cross pigs had a CTP scan prior to injection of endothelin-1 (ET-1) into the left striatum. CTP scans were used to monitor ischemic progression. A second dose of ET-1 was injected 2 h from the first injection. The animal was moved to a 3-T MRI scanner where DWI was performed. CTP imaging was acquired immediately after the MR imaging. Next, the brain was removed and stained with tetrazolium chloride (TTC). Linear regression and Bland-Altman plots were used to correlate the PIV measured by each imaging modality to that of the TIV from the histological gold standard. The CTP-cerebral blood flow (CBF) parameter had the highest R (2) value and slope closest to unity, while the CTP-cerebral blood volume (CBV) had the lowest R(2) value and slope furthest away from unity. The CTP-CBF • CBV product parameter had a higher R(2) value but lower slope than both MR parameers. The best Bland-Altman agreement was observed with the CTP-CBF parameter. PIV from MR-DWI, ADC, and CTP-CBF overestimated the TIV defined with histology. We show that the PIV defined with absolute gray and white matter CT-CBF thresholds correlates best with the TIV and is similar to both MR-DWI and ADC-defined PIVs. Further, the acute CBF • CBV mismatch may not indicate penumbral tissue in the acute stroke setting.

  5. Voluntary suppression of hyperthermia-induced hyperventilation mitigates the reduction in cerebral blood flow velocity during exercise in the heat.

    PubMed

    Tsuji, Bun; Honda, Yasushi; Ikebe, Yusuke; Fujii, Naoto; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-04-15

    Hyperthermia during prolonged exercise leads to hyperventilation, which can reduce arterial CO2 pressure (PaCO2 ) and, in turn, cerebral blood flow (CBF) and thermoregulatory response. We investigated 1) whether humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise and 2) the effects of voluntary breathing control on PaCO2 , CBF, sweating, and skin blood flow. Twelve male subjects performed two exercise trials at 50% of peak oxygen uptake in the heat (37°C, 50% relative humidity) for up to 60 min. Throughout the exercise, subjects breathed normally (normal-breathing trial) or they tried to control their minute ventilation (respiratory frequency was timed with a metronome, and target tidal volumes were displayed on a monitor) to the level reached after 5 min of exercise (controlled-breathing trial). Plotting ventilatory and cerebrovascular responses against esophageal temperature (Tes) showed that minute ventilation increased linearly with rising Tes during normal breathing, whereas controlled breathing attenuated the increased ventilation (increase in minute ventilation from the onset of controlled breathing: 7.4 vs. 1.6 l/min at +1.1°C Tes; P < 0.001). Normal breathing led to decreases in estimated PaCO2 and middle cerebral artery blood flow velocity (MCAV) with rising Tes, but controlled breathing attenuated those reductions (estimated PaCO2 -3.4 vs. -0.8 mmHg; MCAV -10.4 vs. -3.9 cm/s at +1.1°C Tes; P = 0.002 and 0.011, respectively). Controlled breathing had no significant effect on chest sweating or forearm vascular conductance (P = 0.67 and 0.91, respectively). Our results indicate that humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise, and this suppression mitigates changes in PaCO2 and CBF.

  6. 4(α-L-RHAMNOSYLOXY)-BENZYL ISOTHIOCYANATE, A BIOACTIVE PHYTOCHEMICAL THAT DEFENDS CEREBRAL TISSUE AND PREVENTS SEVERE DAMAGE INDUCED BY FOCAL ISCHEMIA/REPERFUSION.

    PubMed

    Galuppo, M; Giacoppo, S; Iori, R; De Nicola, G R; Milardi, D; Bramanti, P; Mazzon, E

    2015-01-01

    Natural compounds are a promising source to treat several pathologies. The present study shows the in vivo pharmacological beneficial effect of 4(α-L-rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) obtained from glucomoringin (GMG; 4(α;-L-rhamnosyloxy)- benzyl glucosinolate), purified from Moringa oleifera seeds and hydrolyzed by myrosinase enzyme (β-thioglucoside glucohydrolase; E.C. 3.2.1.147). Cerebral ischemia/reperfusion (CIR) was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. GMG-ITC (3.5 mg GMG/ml plus 30 μl enzyme/rat; one ml i.p./rat) was administered 15 min after the beginning of ischemia and daily. The results clearly show that GMG-ITC possesses the capability to counteract the CIR-induced damage reducing TNF-alpha release, IκB-alpha cytosolic degradation/NFκBp65 nuclear translocation, as well as several other direct or indirect markers of inflammation (phospho-ERK p42/44, p-selectin) and oxidative stress (inducible Nitric Oxide Synthase (iNOS), MMP-9). GMG-ITC was shown to exert neuroprotective properties in preventing CIR-induced damage and the related cascade of inflammatory and oxidative mediators that exacerbate the progression of this disease in an experimental rat model. Our results clearly show that the tested phytochemical GMG-ITC possesses the capability to counteract CIR-induced damage.

  7. Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma: efficacy and safety results from a large mono-institutional analysis

    PubMed Central

    2010-01-01

    More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting microspheres in terms of response rate (RR), time to progression (TTP), overall survival (OS) and toxicity in HCC. Patients with HCC undergoing traditional TACE or pTACE (either alone or in combination with other treatment options) were eligible One hundred and fifty patients were analyzed. In the global patient population median OS was 46 months for lipiodol TACE and 19 months for pTACE (p < 0.0001), TTP was 30 months versus 16 months for patients receiving TACE or pTACE respectively (p = 0.003). These results were confirmed also among the group of patients who received exclusive TACE or pTACE. Neither RR nor toxicity was different between TACE or pTACE. At multivariate analysis, age, the Okuda stage, type of TACE and number of TACE proved to be independent prognostic factors influencing overall survival. In our experience, lipiodol TACE showed a better OS and TTP over pTACE, without difference in toxicity profile and RR. Among the staging systems analyzed only the Okuda stage seemed able to reliably predict patients outcome. PMID:21159184

  8. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats

    PubMed Central

    Paredes, Sergio D.; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A.F.

    2015-01-01

    Abstract Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription–polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury. PMID:26594596

  9. Impact of hyperthermia before and during ischemia-reperfusion on neuronal damage and gliosis in the gerbil hippocampus induced by transient cerebral ischemia.

    PubMed

    Kim, Min Joung; Cho, Jun Hwi; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Tae, Hyun-Jin; Cho, Geum-Sil; Yan, Bing Chun; Hwang, In Koo; Lee, Choong Hyun; Bae, Eun Joo; Won, Moo-Ho; Lee, Jae-Chul

    2015-01-15

    Hyperthermia can exacerbate the brain damage produced by ischemia. In the present study, we investigated the effects of hyperthermia before and during ischemia-reperfusion on neuronal damage and glial changes in the gerbil hippocampus following transient cerebral ischemia using cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining. The animals were randomly assigned to 4 groups: (1) sham-operated animals with normothermia (normothermia + sham group); (2) ischemia-operated animals with normothermia (normothermia + ischemia group); (3) sham-operated animals with hyperthermia (hyperthermia + sham group); and (4) ischemia-operated animals with hyperthermia (hyperthermia + ischemia group). Hyperthermia (39.5 ± 0.2°C) was induced by exposing the gerbils to a heating pad connected to a rectal thermistor for 30 min before and during ischemia-reperfusion. In the normothermia+ischemia groups, a significant delayed neuronal death was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) 5 days after ischemia-reperfusion. In the hyperthermia+ischemia groups, neuronal death in the SP of the CA1 occurred at 1 day post-ischemia, and neuronal death was observed in the SP of the CA2/3 region at 2 days post-ischemia. In addition, we examined activations of astrocytes and microglia using immunohistochemistry for anti-glial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1). GFAP-positive astrocytes and Iba-1-positive microglia in the ischemic hippocampus were activated much earlier and much more accelerated in the hyperthermia+ischemia groups than those in the normothermia+ischemia groups. Based on our findings, we suggest that an experimentally hyperthermic pre-condition before cerebral ischemic insult produces more extensive neuronal damage and glial activation in the ischemic hippocampus.

  10. Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis

    PubMed Central

    Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

    2016-01-01

    Background and Purpose Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Methods Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger’s test were obtained to detect publication bias. Results We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. Conclusions This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA. PMID:27387385

  11. Dietary Sutherlandia and Elderberry Mitigate Cerebral Ischemia-Induced Neuronal Damage and Attenuate p47phox and Phospho-ERK1/2 Expression in Microglial Cells

    PubMed Central

    Chuang, Dennis Y.; Cui, Jiankun; Simonyi, Agnes; Engel, Victoria A.; Chen, Shanyan; Fritsche, Kevin L.; Thomas, Andrew L.; Applequist, Wendy L.; Folk, William R.; Lubahn, Dennis B.; Sun, Albert Y.; Sun, Grace Y.

    2014-01-01

    Sutherlandia (Sutherlandia frutescens) and elderberry (Sambucus spp.) are used to promote health and for treatment of a number of ailments. Although studies with cultured cells have demonstrated antioxidative and anti-inflammatory properties of these botanicals, little is known about their ability to mitigate brain injury. In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion (I/R) revealed significant reduction in neuronal cell death in both dietary groups. Immunohistochemical staining for ionized calcium-binding adapter molecule-1 demonstrated pronounced activation of microglia in the hippocampus and striatum in the ischemic brains 3 days after I/R, and microglial activation was significantly reduced in animals fed supplemented diets. Mitigation of microglial activation by the supplements was further supported by the decrease in expression of p47phox, a cytosolic subunit of NADPH oxidase, and phospho-ERK1/2, a mitogen-activated protein kinase known to mediate a number of cytoplasmic processes including oxidative stress and neuroinflammatory responses. These results demonstrate neuroprotective effect of Sutherlandia and American elderberry botanicals against oxidative and inflammatory responses to cerebral I/R. PMID:25324465

  12. Maturation and long-term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility.

    PubMed

    Goyal, Ravi; Mittal, Ashwani; Chu, Nina; Arthur, Rebecca Afiba; Zhang, Lubo; Longo, Lawrence D

    2010-11-01

    In the developing fetus, cerebral arteries (CA) show striking differences in signal transduction mechanisms compared with the adult, and these differences are magnified in response to high-altitude long-term hypoxia (LTH). In addition, in the mature organism, cerebrovascular acclimatization to LTH may be associated with several clinical problems, the mechanisms of which are unknown. Because PKC plays a key role in regulating CA contractility, in fetal and adult cerebral arteries, we tested the hypothesis that LTH differentially regulates the PKC-mediated Ca(2+) sensitization pathways and contractility. In four groups of sheep [fetal normoxic (FN), fetal hypoxic (FH), adult normoxic (AN), and adult hypoxic (AH)], we examined, simultaneously, responses of CA tension and intracellular Ca(2+) concentration and measured CA levels of PKC, ERK1/2, RhoA, 20-kDa myosin light chain, and the 17-kDa PKC-potentiated myosin phosphatase inhibitor CPI-17. The PKC activator phorbol 12,13-dibutyrate (PDBu) produced robust contractions in all four groups. However, PDBu-induced contractions were significantly greater in AH CA than in the other groups. In all CA groups except AH, in the presence of MEK inhibitor (U-0126), the PDBu-induced contractions were increased a further 20-30%. Furthermore, in adult CA, PDBu led to increased phosphorylation of ERK1, but not ERK2; in fetal CA, the reverse was the case. PDBu-stimulated ERK2 phosphorylation also was significantly greater in FH than FN CA. Also, although RhoA/Rho kinase played a significant role in PDBu-mediated contractions of FN CA, this was not the case in FH or either adult group. Also, whereas CPI-17 had a significant role in adult CA contractility, this was not the case for the fetus. Overall, in ovine CA, the present study demonstrates several important maturational and LTH acclimatization changes in PKC-induced contractile responses and downstream pathways. The latter may play a key role in the pathophysiologic disorders

  13. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-04-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

  14. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

    PubMed Central

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-01-01

    Abstract. Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity. PMID:25900145

  15. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Thangarajeswari, Mohan; Usha, Ramakrishnan

    2015-01-01

    L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

  16. Cerebral Area Differential Redox Response of Neonatal Rats to Selenite-Induced Oxidative Stress and to Concurrent Administration of Highbush Blueberry Leaf Polyphenols.

    PubMed

    Ferlemi, Anastasia-Varvara; Mermigki, Penelope G; Makri, Olga E; Anagnostopoulos, Dimitrios; Koulakiotis, Nikolaos S; Margarity, Marigoula; Tsarbopoulos, Anthony; Georgakopoulos, Constantinos D; Lamari, Fotini N

    2015-11-01

    Our goal was to delineate the mechanisms of selenite-induced oxidative stress in neonatal rats and investigate the potential of blueberry leaf polyphenols to counteract the induced stress. Vaccinium corymbosum leaf decoction (BLD) was analyzed by UPLC-MS and LC-DAD, along with its in vitro antioxidant activity (DPPH radical scavenging, FRAP, ferrous chelation). Newborn suckling Wistar rats were randomly divided into three groups: 'Se' and 'SeBLD' received 20 μmol Na2SeO3/kg BW subcutaneously (PN day 10); 'SeBLD' received 100 mg dry BLD/kg BW intraperitoneally (PN11 and 12) and Group 'C' received normal saline. Βiochemical analysis revealed tissue-specific effects of selenite. Brain as a whole was more resistant to selenite toxicity in comparison to liver; midbrain and cerebellum were in general not affected, but cortex was moderately disturbed. Liver lipid peroxidation, GSH, SOD, CAT, GPx were significantly affected, whereas proteolytic activity was not. BLD, which is rich in chlorogenic acid and flavonols (especially quercetin derivatives), exerted significant antioxidant protective effects in all regions. In conclusion, we provide for the first time an insight to the neonatal rat cerebral and liver redox response against a toxic selenite dose and blueberry leaf polyphenols.

  17. Withdrawal from fixed-dose injection of methamphetamine decreases cerebral levels of 3-methoxy-4-hydroxyphenylglycol and induces the expression of anxiety-related behavior in mice.

    PubMed

    Kitanaka, Nobue; Kitanaka, Junichi; Tatsuta, Tomohiro; Tanaka, Koh-ichi; Watabe, Kaname; Nishiyama, Nobuyoshi; Morita, Yoshio; Takemura, Motohiko

    2010-05-01

    A variety of drug treatment regimens have been proposed to model the dysphoric state observed during methamphetamine (METH) withdrawal in rats, but little has been established in experiments using mice. In male ICR mice, a fixed-dose injection regimen of METH (1.0 or 2.5 mg/kg, i.p., twice daily for 10 consecutive days) induced a significant decrease in the time spent in open arms in an elevated plus maze after 5 days of drug abstinence. Under an escalating-dose injection regimen (0.2-2.0 mg/kg, i.p., 3 times daily for 4 days, total: 15 mg/kg/animal) or continuous subcutaneous administration with osmotic mini-pumps (15 or 76 mg/kg of METH for 2 weeks), no significant behavioral change was observed after 5 days of drug abstinence, compared with control animals. Reduced gains in body weight were observed during repeated treatment with METH in the fixed-dose injection and mini-pump treatment regimens, but not the escalating-dose injection regimen. HPLC analysis revealed significant decreases in the level of cerebral 3-methoxy-4-hydroxyphenylglycol, a norepinephrine metabolite, and norepinephrine turnover, which may be attributed to the expression of anxiety-related behavior in the elevated plus maze. These observations suggest that the mice treated with a fixed-dose of METH may model the anxiety-related behavior observed in the dysphoric state induced by METH withdrawal in humans.

  18. Maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine Borrelia and Plasmodium co-infection model.

    PubMed

    Normark, Johan; Nelson, Maria; Engström, Patrik; Andersson, Marie; Björk, Rafael; Moritz, Thomas; Fahlgren, Anna; Bergström, Sven

    2014-01-01

    In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.

  19. Ethanol exposure during neurogenesis induces persistent effects on neural maturation: evidence from an ex vivo model of fetal cerebral cortical neuroepithelial progenitor maturation.

    PubMed

    Camarillo, Cynthia; Miranda, Rajesh C

    2008-01-01

    Ethanol is a significant neuroteratogen. We previously used fetal cortical-derived neurosphere cultures as an ex vivo model of the second trimester ventricular neuroepithelium, and showed that ethanol directly induced fetal stem and progenitor cell proliferation and maturation without inducing death. However, ethanol is defined as a teratogen because of its capacity to persistently disrupt neural maturation beyond a specific exposure period. We therefore utilized a simplified neuronal maturation paradigm to examine the immediate and persistent changes in neuronal migration following ethanol exposure during the phase of neuroepithelial proliferation. Our data indicate that mRNA transcripts for migration-associated genes RhoA, Paxillin (Pxn), and CDC42 were immediately induced following ethanol exposure, whereas dynein light chain, LC8-type 1 (DYNLL1), and growth-associated protein (Gap)-43 were suppressed. With the exception of Gap43, ethanol did not induce persistent changes in the other mRNAs, suggesting that ethanol had an activational, rather than organizational, impact on migration-associated mRNAs. However, despite this lack of persistent effects on these mRNAs, ethanol exposure during the proliferation period significantly increased subsequent neuronal migration. Moreover, differentiating neurons, pretreated with ethanol during the proliferation phase, exhibited reduced neurite branching and an increased length of primary neurites, indicating a persistent destabilization of neuronal maturation. Collectively, our data indicate that ethanol-exposed proliferating neuroepithelial precursors exhibit subsequent differentiation-associated increases in migratory behavior, independent of mRNA transcript levels. These data help explain the increased incidence of cerebral cortical neuronal heterotopias associated with the fetal alcohol syndrome.

  20. Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice.

    PubMed

    de Freitas, Andressa Sausen; Funck, Vinícius Rafael; Rotta, Mariana dos Santos; Bohrer, Denise; Mörschbächer, Vanessa; Puntel, Robson Luís; Nogueira, Cristina Wayne; Farina, Marcelo; Aschner, Michael; Rocha, João Batista Teixeira

    2009-04-06

    Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe)2), a structurally simple organoselenium compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o.), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c.) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate MeHg-induced

  1. The role of the cerebral ganglia in the venom-induced behavioral manipulation of cockroaches stung by the parasitoid jewel wasp.

    PubMed

    Kaiser, Maayan; Libersat, Frederic

    2015-04-01

    The jewel wasp stings cockroaches and injects venom into their cerebral ganglia, namely the subesophageal ganglion (SOG) and supraesophageal ganglion (SupOG). The venom induces a long-term hypokinetic state, during which the stung cockroach shows little or no spontaneous walking. It was shown that venom injection to the SOG reduces neuronal activity, thereby suggesting a similar effect of venom injection in the SupOG. Paradoxically, SupOG-ablated cockroaches show increased spontaneous walking in comparison with control. Yet most of the venom in the SupOG of cockroaches is primarily concentrated in and around the central complex (CX). Thus the venom could chiefly decrease activity in the CX to contribute to the hypokinetic state. Our first aim was to resolve this discrepancy by using a combination of behavioral and neuropharmacological tools. Our results show that the CX is necessary for the initiation of spontaneous walking, and that focal injection of procaine to the CX is sufficient to induce the decrease in spontaneous walking. Furthermore, it was shown that artificial venom injection to the SOG decreases walking. Hence our second aim was to test the interactions between the SupOG and SOG in the venom-induced behavioral manipulation. We show that, in the absence of the inhibitory control of the SupOG on walking initiation, injection of venom in the SOG alone by the wasp is sufficient to induce the hypokinetic state. To summarize, we show that venom injection to either the SOG or the CX of the SupOG is, by itself, sufficient to decrease walking.

  2. Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after Global Cerebral Ischemia Induced by Cardiac Arrest in Rats

    PubMed Central

    Wang, Peng; Yao, Lan; Zhou, Li-li; Liu, Yuan-shan; Chen, Ming-di; Wu, Hai-dong; Chang, Rui-ming; Li, Yi; Zhou, Ming-gen; Fang, Xiang-shao; Yu, Tao; Jiang, Long-yuan; Huang, Zi-tong

    2016-01-01

    Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis. PMID:27489503

  3. Characterization of the Molecular Mechanisms Underlying the Chronic Phase of Stroke in a Cynomolgus Monkey Model of Induced Cerebral Ischemia.

    PubMed

    Law, Henry C H; Szeto, Samuel S W; Quan, Quan; Zhao, Yun; Zhang, Zaijun; Krakovska, Olga; Lui, Leong Ting; Zheng, Chengyou; Lee, Simon M-Y; Siu, K W Michael; Wang, Yuqiang; Chu, Ivan K

    2017-03-03

    Stroke is one of the main causes of mortality and long-term disability worldwide. The pathophysiological mechanisms underlying this disease are not well understood, particularly in the chronic phase after the initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode, was evaluated using qualitative and quantitative proteomics analyses. By using multiple online multidimensional liquid chromatography platforms, 8790 nonredundant proteins were identified that condensed to 5223 protein groups at 1% global false discovery rate (FDR). After the application of a conservative criterion (5% local FDR), 4906 protein groups were identified from the analysis of cerebral cortex. Of the 2068 quantified proteins, differential proteomic analyses revealed that 31 and 23 were dysregulated in the elevated- and low-infarct-volume groups, respectively. Neurogenesis, synaptogenesis, and inflammation featured prominently as the cellular processes associated with these dysregulated proteins. Protein interaction network analysis revealed that the dysregulated proteins for inflammation and neurogenesis were highly connected, suggesting potential cross-talk between these processes in modulating the cytoskeletal structure and dynamics in the chronic phase poststroke. Elucidating the long-term consequences of brain tissue injuries from a cellular prospective, as well as the molecular mechanisms that are involved, would provide a basis for the development of new potentially neurorestorative therapies.

  4. Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion.

    PubMed

    Cheng, Pengfei; Zuo, Xuzheng; Ren, Yifei; Bai, Shunjie; Tang, Weiju; Chen, Xiuying; Wang, Gong; Wang, Haoxiang; Huang, Wen; Xie, Peng

    2016-12-01

    We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-α reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH.

  5. Flow-induced wall mechanics of patient-specific aneurysmal cerebral arteries: Nonlinear isotropic versus anisotropic wall stress.

    PubMed

    Cornejo, Sergio; Guzmán, Amador; Valencia, Alvaro; Rodríguez, Jose; Finol, Ender

    2014-01-01

    Fluid-structure interaction simulations of three patient-specific models of cerebral aneurysms were carried out with the objective of quantifying the effects of non-Newtonian blood flow and the vessel mechanical behavior on the time-dependent fluid shear and normal stresses, and structural stress and stretch. The average wall shear stress at peak systole was found to be approximately one order of magnitude smaller than the shear stresses in the proximal communicating arteries, regardless of the shape or size of the aneurysms. Spatial distributions of oscillatory shear index were consistent with the reciprocal of wall shear stress distributions at peak systole for all aneurysm geometries, demonstrating that oscillatory shear index correlates inversely with wall shear at this time point in the cardiac cycle. An aneurysm wall modeled with an isotropic material resulted in an underestimation of both the maximum principal stress and stretch, compared to the anisotropic material model. For the three aneurysm geometries, anisotropic peak wall stresses were approximately 50% higher than for an isotropic material. Regardless of the constitutive material, the maximum stresses were consistently located at the aneurysm neck; stresses in the dome were 30% of those in the neck.

  6. Neurological and histological consequences induced by in vivo cerebral oxidative stress: evidence for beneficial effects of SRT1720, a sirtuin 1 activator, and sirtuin 1-mediated neuroprotective effects of poly(ADP-ribose) polymerase inhibition.

    PubMed

    Gueguen, Cindy; Palmier, Bruno; Plotkine, Michel; Marchand-Leroux, Catherine; Besson, Valérie C

    2014-01-01

    Poly(ADP-ribose)polymerase and sirtuin 1 are both NAD(+)-dependent enzymes. In vitro oxidative stress activates poly(ADP-ribose)polymerase, decreases NAD(+) level, sirtuin 1 activity and finally leads to cell death. Poly(ADP-ribose)polymerase hyperactivation contributes to cell death. In addition, poly(ADP-ribose)polymerase inhibition restores NAD(+) level and sirtuin 1 activity in vitro. In vitro sirtuin 1 induction protects neurons from cell loss induced by oxidative stress. In this context, the role of sirtuin 1 and its involvement in beneficial effects of poly(ADP-ribose)polymerase inhibition were evaluated in vivo in a model of cerebral oxidative stress induced by intrastriatal infusion of malonate in rat. Malonate promoted a NAD(+) decrease that was not prevented by 3-aminobenzamide, a poly(ADP-ribose)polymerase inhibitor, at 4 and 24 hours. However, 3-aminobenzamide increased nuclear SIRT1 activity/expression ratio after oxidative stress. Malonate induced a neurological deficit associated with a striatal lesion. Both were reduced by 3-aminobenzamide and SRT1720, a sirtuin 1 activator, showing beneficial effects of poly(ADP-ribose)polymerase inhibition and sirtuin 1 activation on oxidative stress consequences. EX527, a sirtuin 1 inhibitor, given alone, modified neither the score nor the lesion, suggesting that endogenous sirtuin 1 was not activated during cerebral oxidative stress. However, its association with 3-aminobenzamide suppressed the neurological improvement and the lesion reduction induced by 3-aminobenzamide. The association of 3-aminobenzamide with SRT1720, the sirtuin 1 activator, did not lead to a better protection than 3-aminobenzamide alone. The present data represent the first demonstration that the sirtuin 1 activator SRT1720 is neuroprotective during in vivo cerebral oxidative stress. Furthermore sirtuin 1 activation is involved in the beneficial effects of poly(ADP-ribose)polymerase inhibition after in vivo cerebral oxidative stress.

  7. Dexmedetomidine alleviates cerebral ischemia-induced short-term memory impairment by inhibiting the expression of apoptosis-related molecules in the hippocampus of gerbils

    PubMed Central

    Choi, In-Young; Hwang, Lakkyong; Jin, Jun-Jang; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Shin, Key-Moon; Kim, Chang-Ju; Park, Sung-Wook; Han, Jin-Hee; Yi, Jae-Woo

    2017-01-01

    Cerebral ischemia results from cerebrovascular occlusion, which leads to neuronal cell death and eventually causes neurological impairments. Dexmedetomidine is a potent and highly selective α2-adrenoreceptor agonist with actions such as sedation, anxiolysis, analgesia and anesthetic-sparing effects. We investigated the effect of dexmedetomidine on apoptosis in the hippocampus after transient global ischemia in gerbils. Transient global ischemia was induced by ligation of both common carotid arteries. Dexmedetomidine was administrated intraperitoneally at three respective doses (0.1, 1 and 10 µg/kg) once per day for 14 consecutive days beginning a day after surgery. Short-term memory was assessed by use of a step-down avoidance task. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, immunohistochemistry for caspase-3, and western blot analysis of Bcl-2-associated X protein, B-cell lymphoma 2, Bid, cytochrome c, apoptotic protease activating factor-1 and caspase-9 in the hippocampus. Induction of global ischemia deteriorated short-term memory by enhancing the expression of apoptosis-related molecules in the hippocampus. Treatment with dexmedetomidine suppressed the expression of apoptosis-related molecules under ischemic conditions, resulting in short-term memory improvement. Under normal conditions, dexmedetomidine exerted no significant effect on apoptosis in the hippocampus. The present results suggest that the α2-adrenoceptor agonist dexmedetomidine may be a useful therapeutic agent for the treatment of ischemic brain diseases. PMID:28123477

  8. PPAR-γ activator induces neuroprotection in hypercholesterolemic rats subjected to global cerebral ischemia/reperfusion injury: in vivo and in vitro inhibition of oxidative stress.

    PubMed

    Al Rouq, Fawzia; El Eter, Eman

    2014-03-01

    Hypercholesterolemia (HC) and aging combine to increase the incidence of cerebrovascular disease through oxidative stress. Our investigation examined the effects of diet-induced hypercholesterolemia (2% for 8weeks) on the extent of brain injury in response to global cerebral ischemia/reperfusion (GCI/R) and the neuroprotective potentials of rosiglitazone in relation to oxidative stress. HC exacerbated the decline in the brain levels of GSH and the increase in MPO, proinflammatory markers and hippocampal lesions in response to GCI/R. HC rats receiving rosiglitazone, PPAR-γ agonist, demonstrated preservation of cell viability of CA1 hippocampal region and attenuation of brain edema. They also showed elevated levels of GSH and low levels of the other parameters similar to non-HC rats subjected to GCI/R. In vitro, rosiglitazone dose-dependently inhibited ROS generation by neutrophils. The results suggest exacerbation of brain lesions by HC in response to GCI/R. The neuroprotective therapeutic potentials of rosiglitazone are comparable to non-HC animals. Mechanisms of protection are possibly due to anti-oxidant, anti-inflammatory effects and scavenging properties of rosiglitazone. These results add to the beneficial therapeutic effects of rosiglitazone and its significance for age-associated diseases including hypercholesterolemia.

  9. Computed tomography guided percutaneous injection of a mixture of lipiodol and methylene blue in rabbit lungs: evaluation of localization ability for video-assisted thoracoscopic surgery.

    PubMed

    Jin, Kwang Nam; Lee, Kyung Won; Kim, Tae Jung; Song, Yong Sub; Kim, Dong Il

    2014-01-01

    Preoperative localization is necessary prior to video assisted thoracoscopic surgery for the detection of small or deeply located lung nodules. We compared the localization ability of a mixture of lipiodol and methylene blue (MLM) (0.6 mL, 1:5) to methylene blue (0.5 mL) in rabbit lungs. CT-guided percutaneous injections were performed in 21 subjects with MLM and methylene blue. We measured the extent of staining on freshly excised lung and evaluated the subjective localization ability with 4 point scales at 6 and 24 hr after injections. For MLM, radio-opacity was evaluated on the fluoroscopy. We considered score 2 (acceptable) or 3 (excellent) as appropriate for localization. The staining extent of MLM was significantly smaller than methylene blue (0.6 vs 1.0 cm, P<0.001). MLM showed superior staining ability over methylene blue (2.8 vs 2.2, P=0.010). Excellent staining was achieved in 17 subjects (81%) with MLM and 8 (38%) with methylene blue (P=0.011). An acceptable or excellent radio-opacity of MLM was found in 13 subjects (62%). An appropriate localization rate of MLM was 100% with the use of the directly visible ability and radio-opacity of MLM. MLM provides a superior pulmonary localization ability over methylene blue.

  10. Gigantic Cavernous Hemangioma of the Liver Treated by Intra-Arterial Embolization with Pingyangmycin-Lipiodol Emulsion: A Multi-Center Study

    SciTech Connect

    Zeng Qingle; Li Yanhao; Chen Yong; Ouyang Yong; He Xiang; Zhang Heping

    2004-09-15

    Purpose: To evaluate the therapeutic effect and safety of pingyangmycin-lipiodol emulsion (PLE) intra-arterial embolization for treating gigantic cavernous hemangioma of the liver (CHL).Methods: Three hospitals (Nanfang Hospital, Inner Mongolia Autonomous Region's Hospital and Huai He Hospital) participated in the study during 1997-2001. A total of 98 patients with CHL were embolized with PLE via the hepatic artery. The therapeutic effects including changes in tumor diameter, symptomatic improvement and occurrence of complications were evaluated for a period of 12 months after the procedure.Results: The tumor diameters decreased significantly from 9.7 {+-} 2.3 cm to 5.6 {+-} 1.6 cm 6 months after the treatment (P < 0.01), and then to 3.0 {+-} 1.2 cm at 12 months (P < 0.01). Transient impairment of liver function was found in 77 cases after embolization, 69 cases of which returned to normal in 2 weeks, and the other eight cases of which recovered 1 month later. The clinical symptoms were significantly relieved in all 53 symptomatic patients. Persistent pain in the hepatic region was found in two cases, and these two patients resorted to surgery eventually.Conclusion: Intra-arterial PLE embolization proves to be effective and safe in treating patients with CHL.

  11. Computed Tomography Guided Percutaneous Injection of a Mixture of Lipiodol and Methylene Blue in Rabbit Lungs: Evaluation of Localization Ability for Video-Assisted Thoracoscopic Surgery

    PubMed Central

    Jin, Kwang Nam; Kim, Tae Jung; Song, Yong Sub; Kim, Dong Il

    2014-01-01

    Preoperative localization is necessary prior to video assisted thoracoscopic surgery for the detection of small or deeply located lung nodules. We compared the localization ability of a mixture of lipiodol and methylene blue (MLM) (0.6 mL, 1:5) to methylene blue (0.5 mL) in rabbit lungs. CT-guided percutaneous injections were performed in 21 subjects with MLM and methylene blue. We measured the extent of staining on freshly excised lung and evaluated the subjective localization ability with 4 point scales at 6 and 24 hr after injections. For MLM, radio-opacity was evaluated on the fluoroscopy. We considered score 2 (acceptable) or 3 (excellent) as appropriate for localization. The staining extent of MLM was significantly smaller than methylene blue (0.6 vs 1.0 cm, P<0.001). MLM showed superior staining ability over methylene blue (2.8 vs 2.2, P=0.010). Excellent staining was achieved in 17 subjects (81%) with MLM and 8 (38%) with methylene blue (P=0.011). An acceptable or excellent radio-opacity of MLM was found in 13 subjects (62%). An appropriate localization rate of MLM was 100% with the use of the directly visible ability and radio-opacity of MLM. MLM provides a superior pulmonary localization ability over methylene blue. PMID:24431917

  12. Selective and persistent deposition and gradual drainage of iodized oil, Lipiodol in the hepatocellular carcinoma after injection into the feeding hepatic artery

    SciTech Connect

    Okayasu, I.; Hatakeyama, S.; Yoshida, T.; Yoshimatsu, S.; Tsuruta, K.; Miyamoto, H.; Kimula, Y.

    1988-11-01

    The selective and long-term deposition of iodized oil in the hepatocellular carcinoma (HCC) and its gradual drainage were clinicopathologically analyzed in 13 cases. All patients were Japanese and had an intrahepatic arterial injection of Lipiodol (LIP) mixed with Mitomycin C. The comparison among the follow-up computerized tomography (CT) findings, the observation of the soft x-ray radiogram, and histopathologic studies of the surgical or autopsy materials revealed that the selective deposition of LIP in HCC lasted for a long term, particularly in cases treated by LIP combined with transcatheter arterial embolization (TAE). Also revealed was an extremely gradual decrease of LIP from the HCC. It was thus postulated that, mainly, the accumulated macrophages surrounding LIP around the necrotic cancer tissue and, partially, the intrahepatic lymphatic system itself contributed to this drainage. Further, in histologic sections with lipid staining, x-ray microanalysis proved that the lipid droplets in the cancer tissue included highly concentrated iodine, as a deposition of LIP.

  13. Baclofen ameliorates spatial working memory impairments induced by chronic cerebral hypoperfusion via up-regulation of HCN2 expression in the PFC in rats.

    PubMed

    Luo, Pan; Chen, Cheng; Lu, Yun; Fu, TianLi; Lu, Qing; Xu, Xulin; Li, Changjun; He, Zhi; Guo, Lianjun

    2016-07-15

    Chronic cerebral hypoperfusion (CCH) causes memory deficits and increases the risk of vascular dementia (VD) through several biologically plausible pathways. However, whether CCH causes prefrontal cortex (PFC)-dependent spatial working memory impairments and Baclofen, a GABAB receptor agonist, could ameliorate the impairments is still not clear especially the mechanisms underlying the process. In this study, rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. Two weeks later, rats were treated with 25mg/kg Baclofen (intraperitioneal injection, i.p.) for 3 weeks. Spatial working memory was evaluated in a Morris water maze using a modified delayed matching-to-place (DMP) procedure. Western blotting and immunohistochemistry were used to quantify the protein levels and protein localization. Our results showed that 2VO caused striking spatial working memory impairments, accompanied with a decreased HCN2 expression in PFC, but the protein levels of protein gene product 9.5 (PGP9.5, a neuron specific protein), glial fibrillary acidic protein (GFAP), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), parvalbumin (PV) and HCN1 were not distinguishably changed as compared with sham-operated rats. Baclofen treatment significantly improved the spatial working memory impairments caused by 2VO, accompanied with a reversion of 2VO-induced down-regulation of HCN2. Furthermore, there was a co-localization of HCN2 subunits and parvalbumin-positive neurons in PFC. Therefore, HCN2 may target inhibitory interneurons that is implicated in working memory processes, which may be a possible mechanism of the up-regulation of HCN2 by Baclofen treatment that reliefs spatial working memory deficits in rats with CCH.

  14. NEUROPROTECTIVE PROPERTIES OF MARROW-ISOLATED ADULT MULTILINEAGE INDUCIBLE CELLS IN RAT HIPPOCAMPUS FOLLOWING GLOBAL CEREBRAL ISCHEMIA ARE ENHANCED WHEN COMPLEXED TO BIOMIMETIC MICROCARRIERS

    PubMed Central

    Garbayo, E.; Raval, A.P.; Curtis, K.M.; Della-Morte, D.; Gomez, L.A.; D'Ippolito, G.; Reiner, T.; Perez-Stable, C.; Howard, G.A.; Perez-Pinzon, M.A.; Montero-Menei, C.N.; Schiller, P.C.

    2015-01-01

    Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of Marrow-Isolated Adult Multilineage Inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD) and rats subjected to asphyxial cardiac arrest (ACA). We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with EGF/bFGF pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Naïve and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after OGD and ACA, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed βIII-Tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells. PMID:21496021

  15. Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway

    PubMed Central

    Wang, Zhihua; Ye, Zhi; Huang, Guoqing; Wang, Na; Wang, E.; Guo, Qulian

    2016-01-01

    The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway. PMID:27965539

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

    SciTech Connect

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

    2007-04-15

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

  17. Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway.

    PubMed

    Wang, Zhihua; Ye, Zhi; Huang, Guoqing; Wang, Na; Wang, E; Guo, Qulian

    2016-01-01

    The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

  18. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway

    SciTech Connect

    Chen, T.-G.; Chen, T.-L.; Chang, H.-C.; Tai, Y.-T.; Cherng, Y.-G.; Chang, Y.-T.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  19. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway.

    PubMed

    Chen, Tyng-Guey; Chen, Ta-Liang; Chang, Huai-Chia; Tai, Yu-Ting; Cherng, Yih-Giun; Chang, Ya-Ting; Chen, Ruei-Ming

    2007-02-15

    Cerebral endothelial cells (CECs) are crucial components of the blood-brain barrier. Oxidized low-density lipoprotein (oxLDL) can induce cell injuries. In this study, we attempted to evaluate the effects of oxLDL on mouse CECs and its possible mechanisms. Mouse CECs were isolated from brain tissues and identified by immunocytochemical staining of vimentin and Factor VIII. oxLDL was prepared from LDL oxidation by copper sulfate. Exposure of mouse CECs to oxLDL decreased cell viability in concentration- and time-dependent manners. oxLDL time-dependently caused shrinkage of cell morphologies. Administration of oxLDL to CECs induced DNA fragmentation in concentration- and time-dependent manners. Analysis of the cell cycle revealed that oxLDL concentration- and time-dependently increased the proportion of CECs which underwent apoptosis. Analysis of confocal microscopy and immunoblot revealed that oxLDL significantly increased cellular and mitochondrial Bax levels as well as the translocation of this proapoptotic protein from the cytoplasm to mitochondria. In parallel with the increase in the levels and translocation of Bax, oxLDL time-dependently decreased the mitochondrial membrane potential. Exposure of mouse CECs to oxLDL decreased the amounts of mitochondrial cytochrome c, but enhanced cytosolic cytochrome c levels. The amounts of intracellular reactive oxygen species were significantly augmented after oxLDL administration. Sequentially, oxLDL increased activities of caspase-9, -3, and -6 in time-dependent manners. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, significantly decreased caspase-6 activity and the oxLDL-induced DNA fragmentation and cell apoptosis. This study showed that oxLDL induces apoptotic insults to CECs via signal-transducing events, including enhancing Bax translocation, mitochondrial dysfunction, cytochrome c release, increases in intracellular reactive oxygen species, and cascade activation of caspase-9, -3, and -6. Therefore, ox

  20. The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics

    PubMed Central

    Fuenmayor, Luis D.; Vogt, Marthe

    1979-01-01

    1 Catalepsy was produced in rats and mice by the subcutaneous injection of either tetrabenazine or the butyrophenone U-32,802A (4′-fluoro-4-{[4-(p-fluorophenyl)-3-cyclohexen-1-yl]amino} butyrophenone hydrochloride). Catalepsy was evaluated by the duration of total immobility on a vertical grid. 2 Pretreatment with p-chlorophenylalanine (PCPA) reduced the intensity of catalepsy by 50% or more, whereas its time course remained the same. 3 5-Hydroxytryptophan (5-HTP), 10 mg/kg, enhanced the catalepsy induced by U-32,802A or tetrabenazine, provided it was administered soon (45 min) after the neuroleptic; injections at 90 min had no effect. Otherwise untreated rats given this dose of 5-HTP behaved normally on the grid. 4 The anticataleptic effect of PCPA was reversed by 5-HTP. 5 Measurable changes in 5-hydroxytryptamine (5-HT) metabolism in the rat forebrain accompanied the modification of catalepsy by 5-HTP and PCPA. 6 Methysergide (5 mg/kg) given 30 min before the neuroleptics to either mice or rats reduced the catalepsy, assessed 2.5 h after the methysergide. It also prevented the increase in neuroleptic-induced catalepsy following 5-HTP, 10 mg/kg. 7 Tryptophan, like 5-HTP, increased the catalepsy seen in mice after U-32,802A and tetrabenazine, and increased the production of 5-hydroxyindol-3-ylacetic acid in the forebrain. 8 In the rat, intracerebroventricular injection of physostigmine produced catalepsy which was not modified by methysergide or PCPA but was abolished by atropine. Similarly, in the mouse, catalepsy induced by the subcutaneous injection of pilocarpine was abolished by atropine but not affected by either methysergide or 5-HTP. 9 Atropine greatly reduced the catalepsy induced by U-32,802A and tetrabenazine but lowered striatal homovanillic acid (HVA) only after U-32,802A. D,L-DOPA, 20 mg/kg, diminished the cataleptogenic effect of both neuroleptics and raised striatal HVA. 10 The results support the view that there is a facilitating or permissive

  1. Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles.

    PubMed

    Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung

    2016-03-01

    Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy.

  2. Morphology of elastase-induced cerebral aneurysm model in rabbit and rapid prototyping of elastomeric transparent replicas.

    PubMed

    Seong, Jaehoon; Sadasivan, Chander; Onizuka, Masanari; Gounis, Matthew J; Christian, Fletcher; Miskolczi, Laszlo; Wakhloo, Ajay K; Lieber, Baruch B

    2005-01-01

    In this work, we describe a methodology to fabricate transparent elastomeric vascular replicas using rapid prototyping techniques. First, the three-dimensional morphology of an elastase-induced aneurysm model in rabbit is acquired. The morphology is reconstructed from in vivo rotational angiography and it is compared with three-dimensional reconstructions obtained by computerized tomography and magnetic resonance imaging of an intraluminal arterial cast that was obtained from the same animal at sacrifice. Results show that resolution of the imaging modality strongly influences the level of detail, such as small side branches, in the final reconstruction. We developed an average morphology model for elastase-induced aneurysms in rabbits including the surrounding vasculature and describe a method for rapid prototyping of vascular models from the three-dimensional morphology. Our replicas can be manufactured in a short period of time and the final product is optically clear. In addition, the elasticity of the models can be controlled to represent arterial elasticity, which makes them ideal for optical investigations of detailed flow dynamics using measurement tools such as particle image velocimetry.

  3. Prolonged diet induced obesity has minimal effects towards brain pathology in mouse model of cerebral amyloid angiopathy: implications for studying obesity-brain interactions in mice.

    PubMed

    Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J; Freeman, Linnea R; Pepping, Jennifer K; Beckett, Tina L; Murphy, M Paul; Keller, Jeffrey N

    2013-09-01

    Cerebral amyloid angiopathy (CAA) occurs in nearly every individual with Alzheimer's disease (AD) and Down's syndrome, and is the second largest cause of intracerebral hemorrhage. Mouse models of CAA have demonstrated evidence for increased gliosis contributing to CAA pathology. Nearly two thirds of Americans are overweight or obese, with little known about the effects of obesity on the brain, although increasingly the vasculature appears to be a principle target of obesity effects on the brain. In the current study we describe for the first time whether diet induced obesity (DIO) modulates glial reactivity, amyloid levels, and inflammatory signaling in a mouse model of CAA. In these studies we identify surprisingly that DIO does not significantly increase Aβ levels, astrocyte (GFAP) or microglial (IBA-1) gliosis in the CAA mice. However, within the hippocampal gyri a localized increase in reactive microglia were increased in the CA1 and stratum oriens relative to CAA mice on a control diet. DIO was observed to selectively increase IL-6 in CAA mice, with IL-1β and TNF-α not increased in CAA mice in response to DIO. Taken together, these data show that prolonged DIO has only modest effects towards Aβ in a mouse model of CAA, but appears to elevate some localized microglial reactivity within the hippocampal gyri and selective markers of inflammatory signaling. These data are consistent with the majority of the existing literature in other models of Aβ pathology, which surprisingly show a mixed profile of DIO effects towards pathological processes in mouse models of neurodegenerative disease. The importance for considering the potential impact of ceiling effects in pathology within mouse models of Aβ pathogenesis, and the current experimental limitations for DIO in mice to fully replicate metabolic dysfunction present in human obesity, are discussed. This article is part of a Special Issue entitled: Animal Models of Disease.

  4. Drug delivery to the brain by focused ultrasound induced blood-brain barrier disruption: quantitative evaluation of enhanced permeability of cerebral vasculature using two-photon microscopy.

    PubMed

    Nhan, Tam; Burgess, Alison; Cho, Eunice E; Stefanovic, Bojana; Lilge, Lothar; Hynynen, Kullervo

    2013-11-28

    Reversible and localized blood-brain barrier disruption (BBBD) using focused ultrasound (FUS) in combination with intravascularly administered microbubbles (MBs) has been established as a non-invasive method for drug delivery to the brain. Using two-photon fluorescence microscopy (2 PFM), we imaged the cerebral vasculature during BBBD and observed the extravasation of fluorescent dye in real-time in vivo. We measured the enhanced permeability upon BBBD for both 10 kDa and 70 kDa dextran conjugated Texas Red (TR) at the acoustic pressure range of 0.2-0.8 MPa and found that permeability constants of TR10 kDa and TR70 kDa vary from 0.0006 to 0.0359 min(-1) and from 0.0003 to 0.0231 min(-1), respectively. For both substances, a linear regression was applied on the permeability constant against the acoustic pressure and the slope from best-fit was found to be 0.039 ± 0.005 min(-1)/MPa and 0.018 ± 0.005 min(-1)/MPa, respectively. In addition, the pressure threshold for successfully induced BBBD was confirmed to be 0.4-0.6MPa. Finally, we identified two types of leakage kinetics (fast and slow) that exhibit distinct permeability constants and temporal disruption onsets, as well as demonstrated their correlations with the applied acoustic pressure and vessel diameter. Direct assessment of vascular permeability and insights on its dependency on acoustic pressure, vessel size and leakage kinetics are important for treatment strategies of BBBD-based drug delivery.

  5. TTC, fluoro-Jade B and NeuN staining confirm evolving phases of infarction induced by middle cerebral artery occlusion.

    PubMed

    Liu, Fudong; Schafer, Dorothy P; McCullough, Louise D

    2009-04-30

    Considerable debate exists in the literature on how best to measure infarct damage and at what point after middle cerebral artery occlusion (MCAO) infarct is histologically complete. As many researchers are focusing on more chronic endpoints in neuroprotection studies it is important to evaluate histological damage at later time points to ensure that standard methods of tissue injury measurement are accurate. To compare tissue viability at both acute and sub-acute time points, we used 2,3,5-triphenyltetrazolium chloride (TTC), Fluoro-Jade B, and NeuN staining to examine the evolving phases of infarction induced by a 90-min MCAO in mice. Stroke outcomes were examined at 1.5h, 6h, 12h, 24h, 3d, and 7d after MCAO. There was a time-dependent increase in infarct volume from 1.5h to 24h in the cortex, followed by a plateau from 24h to 7d after stroke. Striatal infarcts were complete by 12h. Fluoro-Jade B staining peaked at 24h and was minimal by 7d. Our results indicated that histological damage as measured by TTC and Fluoro-Jade B reaches its peak by 24h after stroke in a reperfusion model of MCAO in mice. TTC staining can be accurately performed as late as 7d after stroke. Neurological deficits do not correlate with the structural lesion but rather transient impairment of function. As the infarct is complete by 24h and even earlier in the striatum, even the most efficacious neuroprotective therapies are unlikely to show any efficacy if given after this point.

  6. Structural Changes Induced by Daily Music Listening in the Recovering Brain after Middle Cerebral Artery Stroke: A Voxel-Based Morphometry Study

    PubMed Central

    Särkämö, Teppo; Ripollés, Pablo; Vepsäläinen, Henna; Autti, Taina; Silvennoinen, Heli M.; Salli, Eero; Laitinen, Sari; Forsblom, Anita; Soinila, Seppo; Rodríguez-Fornells, Antoni

    2014-01-01

    Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain. PMID:24860466

  7. Logistic regression analyses for predicting clinically important differences in motor capacity, motor performance, and functional independence after constraint-induced therapy in children with cerebral palsy.

    PubMed

    Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Shieh, Jeng-yi; Lu, Lu; Lin, Keh-chung

    2013-03-01

    Given the growing evidence for the effects of constraint-induced therapy (CIT) in children with cerebral palsy (CP), there is a need for investigating the characteristics of potential participants who may benefit most from this intervention. This study aimed to establish predictive models for the effects of pediatric CIT on motor and functional outcomes. Therapists administered CIT to 49 children (aged 3-11 years) with CP. Sessions were 1-3.5h a day, twice a week, for 3-4 weeks. Parents were asked to document the number of restraint hours outside of the therapy sessions. Domains of treatment outcomes included motor capacity (measured by the Peabody Developmental Motor Scales II), motor performance (measured by the Pediatric Motor Activity Log), and functional independence (measured by the Pediatric Functional Independence Measure). Potential predictors included age, affected side, compliance (measured by time of restraint), and the initial level of motor impairment severity. Tests were administered before, immediately after, and 3 months after the intervention. Logistic regression analyses showed that total amount of restraint time was the only significant predictor for improved motor capacity immediately after CIT. Younger children who restrained the less affected arm for a longer time had a greater chance to achieve clinically significant improvements in motor performance. For outcomes of functional independence in daily life, younger age was associated with clinically meaningful improvement in the self-care domain. Baseline motor abilities were significantly predictive of better improvement in mobility and cognition. Significant predictors varied according to the aspects of motor outcomes after 3 months of follow-up. The potential predictors identified in this study allow clinicians to target those children who may benefit most from CIT.

  8. Cerebral Aneurysms

    MedlinePlus

    ... treatment prevents repeat aneurysm rupture by placing a metal clip at the base of the aneurysm. Individuals ... the aneurysm, where it is used to insert metal coils that induce clot formation within the aneurysm. × ...

  9. Cerebral Palsy (For Kids)

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy Print A A ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

  10. Cerebral Palsy (For Kids)

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy A A A ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

  11. Association of cisplatin and intra-arterial injection of {sup 131}I-lipiodol in treatment of hepatocellular carcinoma: Results of phase II trial

    SciTech Connect

    Raoul, Jean-Luc . E-mail: raoul@rennes.fnclcc.fr; Boucher, Eveline; Olivie, Damien; Guillygomarc'h, Anne; Boudjema, Karim; Garin, Etienne

    2006-03-01

    Purpose: Intra-arterial injections of {sup 131}I-lipiodol ({sup 131}I-Lip) provide an effective treatment for hepatocellular carcinoma. In hepatocellular carcinoma cell cultures, concurrent administration of cisplatin increases the cytotoxicity of {sup 131}I. The efficacy and tolerance of intra-arterial injections of {sup 131}I-Lip combined with systemic cisplatin was tested in a phase II trial. Methods and Materials: The inclusion criteria were proven unresectable nonmetastatic hepatocellular carcinoma, compensated liver disease, and adequate laboratory test findings. Treatment comprised the combination of intra-arterial injection of {sup 131}I-Lip (2.2 GBq) with intravenous infusion of low-dose cisplatin. The combined treatment could be repeated. Results: A total of 41 patients were included; 37 had cirrhosis and 38 had measurable tumors. One to four treatments (median, two) were given. The cisplatin dose was 75 mg for the first course and 72 mg for the second. Grade 3-4 (n/n) adverse effects were observed in 14 patients, polymorphonuclear leukocytes (3/0), platelets (5/1), asthenia (1/0), pain (1/0), and vomiting (1/0). Four patients developed pulmonary toxicity; 2 cases were likely related to {sup 131}I-Lip administration and 1 was fatal. The response rate was 47% (18 of 38), and the 1- and 2-year survival rate was 73% {+-} 7% and 48% {+-} 9%, respectively. Conclusion: This combination had a tolerable toxicity profile and provided an objective response rate, warranting a phase III trial.

  12. Nerve growth factor neuroprotection of ethanol-induced neuronal death in rat cerebral cortex is age dependent.

    PubMed

    Mooney, S M; Miller, M W

    2007-10-26

    Organotypic cultures of rat cortex were used to test the hypotheses that nerve growth factor (NGF) is neuroprotective for immature cortical neurons and that ethanol abolishes this neuroprotection in a developmental stage-dependent manner. Samples were obtained on gestational day (G) 16 or postnatal day (P) 3 and cultured with ethanol (0 or 400 mg/dl) and NGF (0 or 30 ng/ml) for 72 h. Dying neurons were identified as exhibiting terminal nick-end labeling, immunoreactivity for activated caspase 3, or condensed nuclear chromatin. Two cortical compartments were examined in fetal tissue: a superficial, cell-sparse marginal zone (MZ) and a cell-dense cortical plate (CP). At P3, the CP was subdivided into a cell-dense upper cortical plate (UCP) and a less densely packed lower cortical plate (LCP). Neuronal death in the MZ was affected by neither NGF nor ethanol at both ages. In the fetal CP, NGF did not affect the incidence of cell death, but ethanol increased it. Treatment with NGF caused an upregulation of the expression of Neg, a gene known to be affected by NGF and ethanol. NGF did not ameliorate the ethanol-induced death. In pups, ethanol increased the amount of death in the LCP. NGF did protect against this death. Neither ethanol nor NGF altered the incidence of cell death in the UCP. The laminar-dependent neuroprotection did not correlate with expression of NGF receptors or Neg. Thus, NGF can be protective against the neurotoxic effect of ethanol in the neonatal brain. This effect is site selective and time dependent and it targets postmigratory, differentiating neurons.

  13. Aging and Cerebral Palsy.

    ERIC Educational Resources Information Center

    Networker, 1993

    1993-01-01

    This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

  14. Estradiol reduces ferrous citrate complex-induced NOS2 up-regulation in cerebral endothelial cells by interfering the nuclear factor kappa B transactivation through an estrogen receptor β-mediated pathway.

    PubMed

    Chen, Li-Ching; Lee, Wen-Sen

    2013-01-01

    Hemorrhagic stroke caused leakage of red blood cells which converts to hemoglobin, heme, and iron accumulated at the lesions. High concentration of ferrous iron from subarachnoid hemorrhage (SAH) induced cerebral vasospasm. Using the two-hemorrhage SAH model in rats, we previously demonstrated that estradiol (E2) significantly attenuated the SAH-induced vasospasm by inhibiting the NOS2 expression. Adding ferrous citrate (FC) complexes to the primary cultured mouse cerebral endothelial cells (CEC) to mimic the SAH conditions, we also showed that FC up-regulates NOS2 through nuclear translocation of NFκB induced by free radicals generation. Here, we further studied the molecular mechanism underlying E2-mediated reduction of the FC-induced up-regulation of NOS2. Treatment with E2 (100 nM) reduced the FC (100 µM)-induced increases of free radical generation and the levels of NOS2 mRNA and protein in the CEC. Moreover, E2 also prevented the FC-induced increases of IκBα phosphorylation, NFκB nuclear translocation, NFκB binding onto the NOS2 promoter, and the NOS2 promoter luciferase activity. However, knock-down the estrogen receptor β (ERβ), but not ERα, abolished the E2-mediated prevention on the FC-induced increases of NOS2 mRNA and protein. The data from the present study suggest that E2 inhibited NOS2 gene expression by interfering with NFκB nuclear translocation and NFκB binding onto the NOS2 through an ERβ-mediated pathway. Our results provide the molecular basis for designing the applicable therapeutic or preventive strategies in the treatment SAH patients.

  15. Monitoring of drug and stimulation induced cerebral blood flow velocity changes in rat sensory cortex using spectral domain Doppler optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Wang, Chuan; Yang, Yong; Ding, Zhihua; Meng, Jie; Wang, Kai; Yang, Wenwei; Xu, Ying

    2011-04-01

    Doppler optical coherence tomography (DOCT) provides a novel method to measure blood flow velocity in vessels with diameter at micrometer scale. In this study, a developed spectral domain DOCT system is applied to monitor cerebral blood flow velocity changes in a rat. An animal model with a cranial window is used, and by application of a drug, light, and electric stimulations, changes in blood flow velocity of the pial artery in sensory cortex are measured in real time. The results show significant differences in blood flow velocity before and after drug administration or light and electric stimulations, demonstrating the feasibility of DOCT in cerebral microcirculation study. Given its noninvasive nature, high spatial resolution, high velocity sensitivity, and high imaging speed, DOCT shows great promise in brain research by imaging blood flow changes at micrometer scale vessels, which helps to understand the pathogenesis of cerebral diseases and neurodegenerative diseases.

  16. Autonomic control of cerebral circulation: exercise.

    PubMed

    Ogoh, Shigehiko

    2008-12-01

    On the basis of measurement techniques that require steady-state hemodynamic conditions when the measurement of cerebral blood flow (CBF) is being obtained, cerebral autoregulation (CA) maintains CBF stable over a wide range of cerebral perfusion pressures. When an acute (or dynamic) change in cerebral perfusion pressure (seconds) is imposed, CBF is not maintained. For example, after thigh cuff occlusion, its release induces an acute drop in arterial blood pressure (ABP). The sharp decrease in CBF indicates that CA was unable to respond to the dynamic (or rapid) changes in cerebral perfusion pressure. Therefore, control mechanisms of arterial pressure with short time constants must contribute importantly to CBF regulation. In order for CA to be effective, the cerebral perfusion pressure must lie within an autoregulatory range of perfusion pressures. The traditional thinking is that changes in sympathetic tone have a limited effect on CBF at rest. However, moderate- to heavy-intensity exercise causes only moderate increases in CBF despite large increases in sympathetic activity and ABP. Animal studies demonstrate that increases in sympathetic nerve activity cause cerebral vasoconstriction and protection against disruption of the blood-brain barrier. These findings suggest that the regulation of CBF during exercise is modulated not only by CA but also by autonomic nervous system and the arterial baroreflex-mediated control of the systemic circulation.

  17. Concise Review: Are Stimulated Somatic Cells Truly Reprogrammed into an ES/iPS-Like Pluripotent State? Better Understanding by Ischemia-Induced Multipotent Stem Cells in a Mouse Model of Cerebral Infarction

    PubMed Central

    Nakagomi, Takayuki; Nakano-Doi, Akiko; Narita, Aya; Matsuyama, Tomohiro

    2015-01-01

    Following the discovery of pluripotent stem (PS) cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells, there has been a great hope that injured tissues can be repaired by transplantation of ES/iPS-derived various specific types of cells such as neural stem cells (NSCs). Although PS cells can be induced by ectopic expression of Yamanaka's factors, it is known that several stimuli such as ischemia/hypoxia can increase the stemness of somatic cells via reprogramming. This suggests that endogenous somatic cells acquire stemness during natural regenerative processes following injury. In this study, we describe whether somatic cells are converted into pluripotent stem cells by pathological stimuli without ectopic expression of reprogramming factors based on the findings of ischemia-induced multipotent stem cells in a mouse model of cerebral infarction. PMID:25945100

  18. Effects of home-based constraint-induced therapy versus dose-matched control intervention on functional outcomes and caregiver well-being in children with cerebral palsy.

    PubMed

    Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

    2011-01-01

    This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21 children with CP (age range, 48-119 months) who were randomly assigned to the CIT or control group. All participants received individualized home-based interventions, 3.5-4h a day, twice a week for 4weeks. Primary outcomes were measured by the Peabody Developmental Motor Scales II (PDMS-2) and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) is the whole name of the assessment. All first letters of this instrument title should be in upper case. Secondary outcome measures were the Pediatric Motor Activity Log (PMAL), the Caregiver Functional Use Survey (CFUS), and the Parenting Stress Index-Short Form (PSI). Outcome measures were performed at baseline (pretreatment), 4weeks (posttreatment), and 6-month (follow-up). Compared with the control group, the CIT group exhibited significantly better performance in grasping control as measured by the PDMS-2, unilateral/bilateral motor efficacy as measured by the BOTMP, and unilateral hand function as measured by the PMAL immediately after the treatment. At the 6-month follow-up, CIT had beneficial effects on grasping control assessed by PDMS-2 and on unilateral/bilateral functional performance measured by the PMAL and CFUS. Parents in both groups reported comparable stress levels at the 6-month follow-up, although the parent-child dysfunctional interaction deteriorated more immediately after CIT than after the control intervention. The follow-up of this randomized controlled trial suggested beneficial effects of home-based CIT on unilateral grasping skills and unilateral/bilateral functional performance at 6 months. The higher stress level reported by the parents in the

  19. Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys

    SciTech Connect

    Porrino, L.J.; Burns, R.S.; Crane, A.M.; Palombo, E.; Kopin, I.J.; Sokoloff, L.

    1987-08-01

    The quantitative 2-deoxy(/sup 14/C) glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different from its effects in the normal monkey.

  20. Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase

    PubMed Central

    Mao, Xiao-Wei; Pan, Chun-Shui; Huang, Ping; Liu, Yu-Ying; Wang, Chuan-She; Yan, Li; Hu, Bai-He; Chang, Xin; He, Ke; Mu, Huan-Na; Li, Quan; Sun, Kai; Fan, Jing-Yu; Han, Jing-Yan

    2015-01-01

    The restoration of blood flow following thrombolytic therapy causes ischemia and reperfusion (I/R) injury leading to blood-brain barrier (BBB) disruption and subsequent brain edema in patients of ischemic stroke. Levo-tetrahydropalmatine (l-THP) occurs in Corydalis genus and some other plants. However, whether l-THP exerts protective role on BBB disrpution following cerebral I/R remains unclear. Male C57BL/6N mice (23 to 28 g) were subjected to 90 min middle cerebral artery occlusion, followed by reperfusion for 24 h. l-THP (10, 20, 40 mg/kg) was administrated by gavage 60 min before ischemia. We found I/R evoked Evans blue extravasation, albumin leakage, brain water content increase, cerebral blood flow decrease, cerebral infarction and neurological deficits, all of which were attenuated by l-THP treatment. Meanwhile, l-THP inhibited tight junction (TJ) proteins down-expression, Src kinase phosphorylation, matrix metalloproteinases-2/9 (MMP-2/9) and caveolin-1 activation. In addition, surface plasmon resonance revealed binding of l-THP to Src kinase with high affinity. Then we found Src kinase inhibitor PP2 could attenuate Evans blue dye extravasation and inhibit the caveolin-1, MMP-9 activation, occludin down-expression after I/R, respectively. In conclusion, l-THP attenuated BBB injury and brain edema, which were correlated with inhibiting the Src kinase phosphorylation. PMID:26059793

  1. Patterns of human local cerebral glucose metabolism during epileptic seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

    1982-10-01

    Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

  2. Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper

    PubMed Central

    2010-01-01

    Background Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A. Methods/Design A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale. Discussion The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of Bo

  3. Statins and cerebral hemodynamics

    PubMed Central

    Giannopoulos, Sotirios; Katsanos, Aristeidis H; Tsivgoulis, Georgios; Marshall, Randolph S

    2012-01-01

    HMG-CoA reductase inhibitors (statins) are associated with improved stroke outcome. This observation has been attributed in part to the palliative effect of statins on cerebral hemodynamics and cerebral autoregulation (CA), which are mediated mainly through the upregulation of endothelium nitric oxide synthase (eNOS). Several animal studies indicate that statin pretreatment enhances cerebral blood flow after ischemic stroke, although this finding is not further supported in clinical settings. Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA. PMID:22929438

  4. Intraaortic Balloon Pump Counterpulsation and Cerebral Autoregulation: an observational study

    PubMed Central

    2010-01-01

    Background The use of Intra-aortic counterpulsation is a well established supportive therapy for patients in cardiac failure or after cardiac surgery. Blood pressure variations induced by counterpulsation are transmitted to the cerebral arteries, challenging cerebral autoregulatory mechanisms in order to maintain a stable cerebral blood flow. This study aims to assess the effects on cerebral autoregulation and variability of cerebral blood flow due to intra-aortic balloon pump and inflation ratio weaning. Methods Cerebral blood flow was measured using transcranial Doppler, in a convenience sample of twenty patients requiring balloon counterpulsation for refractory cardiogenic shock (N = 7) or a single inotrope to maintain mean arterial pressure following an elective placement of an intra-aortic balloon pump for cardiac surgery (N = 13). Simultaneous blood pressure at the aortic root was recorded via the intra-aortic balloon pump. Cerebral blood flow velocities were recorded for six minute intervals at a 1:1 balloon inflation-ratio (augmentation of all cardiac beats) and during progressive reductions of the inflation-ratio to 1:3 (augmentation of one every third cardiac beat). Real time comparisons of peak cerebral blood flow velocities with systolic blood pressure were performed using cross-correlation analysis. The primary endpoint was assessment of cerebral autoregulation using the time delay between the peak signals for cerebral blood flow velocity and systolic blood pressure, according to established criteria. The variability of cerebral blood flow was also assessed using non-linear statistics. Results During the 1:1 inflation-ratio, the mean time delay between aortic blood pressure and cerebral blood flow was -0.016 seconds (95% CI: -0.023,-0.011); during 1:3 inflation-ratio mean time delay was significantly longer at -0.010 seconds (95% CI: -0.016, -0.004, P < 0.0001). Finally, upon return to a 1:1 inflation-ratio, time delays recovered to those measured at

  5. Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia.

    PubMed

    Candelario-Jalil, Eduardo; González-Falcón, Armando; García-Cabrera, Michel; Alvarez, Dalia; Al-Dalain, Said; Martínez, Gregorio; León, Olga Sonia; Springer, Joe E

    2003-08-01

    We investigated the relative contribution of COX-1 and/or COX-2 to oxidative damage, prostaglandin E2 (PGE2) production and hippocampal CA1 neuronal loss in a model of 5 min transient global cerebral ischemia in gerbils. Our results revealed a biphasic and significant increase in PGE2 levels after 2 and 24-48 h of reperfusion. The late increase in PGE2 levels (24 h) was more potently reduced by the highly selective COX-2 inhibitor rofecoxib (20 mg/kg) relative to the COX-1 inhibitor valeryl salicylate (20 mg/kg). The delayed rise in COX catalytic activity preceded the onset of histopathological changes in the CA1 subfield of the hippocampus. Post-ischemia treatment with rofecoxib (starting 6 h after restoration of blood flow) significantly reduced measures of oxidative damage (glutathione depletion and lipid peroxidation) seen at 48 h after the initial ischemic episode, indicating that the late increase in COX-2 activity is involved in the delayed occurrence of oxidative damage in the hippocampus after global ischemia. Interestingly, either selective inhibition of COX-2 with rofecoxib or inhibition of COX-1 with valeryl salicylate significantly increased the number of healthy neurons in the hippocampal CA1 sector even when the treatment began 6 h after ischemia. These results provide the first evidence that both COX isoforms are involved in the progression of neuronal damage following global cerebral ischemia, and have important implications for the potential therapeutic use of COX inhibitors in cerebral ischemia.

  6. Cerebral Asymmetries and Reading Acquisition

    ERIC Educational Resources Information Center

    Pirozzolo, Francis J.

    1978-01-01

    Reviewed are historical developments regarding the concepts of cerebral localization, and analyzed are implications of current research on the role of the cerebral hemispheres in reading disorders. (CL)

  7. Low extracellular magnesium ions induce lipid peroxidation and activation of nuclear factor-kappa B in canine cerebral vascular smooth muscle: possible relation to traumatic brain injury and strokes.

    PubMed

    Altura, Burton M; Gebrewold, Asefa; Zhang, Aimin; Altura, Bella T

    2003-05-08

    The present study was designed to test the hypothesis that administration of low extracellular levels of magnesium ions ([Mg(2+)](o)) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, degradation of IkappaB-alpha, and activation of nuclear transcription factor kappa B (NF-kappaB) in cultured cerebral vascular smooth muscle cells. Low [Mg(2+)](o) (0, 0.15, 0.3 and 0.48 mM) resulted in concentration-dependent rises in malondialdehyde (MDA) in as little as 3 h after exposure to low [Mg(2+)](o), rising to levels 3-12xnormal after 18-24 h; the lower the [Mg(2+)](o), the higher the MDA level. Using electrophoretic mobility shift assays and specific antibodies, low [Mg(2+)](o) caused two DNA-binding proteins (p50, p65) to rise in nuclear extracts in a concentration-dependent manner. High [Mg(2+)](o) (i.e. 4.8 mM) downregulated p50 and p65. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by low [Mg(2+)](o) (in a concentration-dependent manner) and inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These new biochemical and molecular data indicate that low [Mg(2+)](o), in concentrations found in the blood of patients, after traumatic brain injury (TBI) and diverse types of strokes, can elicit rapid lipid peroxidation and activation of NF-kappaB in cerebral vascular smooth muscle cells. The present results, when viewed in light of other recently published data, suggest that low [Mg(2+)](o)-induced lipid peroxidation and activation of NF-kappaB play important roles in TBI and diverse types of strokes.

  8. Cerebral ischemic post-conditioning induces autophagy inhibition and a HMGB1 secretion attenuation feedback loop to protect against ischemia reperfusion injury in an oxygen glucose deprivation cellular model

    PubMed Central

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-01-01

    Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment. Transmission electron microscopy was performed to observe the formation of autophagosomes, and immunofluorescence, western blot and co-immunoprecipitation were used to examine the expression of autophagy-associated proteins and HMGB1. Enzyme-linked immunosorbent assay analysis was conducted to examine the level of HMGB1 in cell supernatants. Additionally, PC12 cells were treated with RAP to examine the effect of autophagy on HMGB1 release, and the effect of recombinant human HMGB1 and Beclin1 small interfering RNA on autophagy was investigated. The present study confirmed that IPOC inhibited autophagy and HMGB1 secretion, autophagy inhibition induced a decrease in HMGB1 secretion, and HMGB1 secretion attenuation caused autophagy inhibition in return, as demonstrated by immunofluorescence and western blot analyses. Autophagy inhibition and HMGB1 secretion attenuation were, therefore, demonstrated to form a feedback loop under IPOC. These mechanisms illustrated the protective effects of IPOC and may accelerate the clinical use of IPOC. PMID:27666823

  9. Cerebral ischemic post‑conditioning induces autophagy inhibition and a HMGB1 secretion attenuation feedback loop to protect against ischemia reperfusion injury in an oxygen glucose deprivation cellular model.

    PubMed

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-11-01

    Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment. Transmission electron microscopy was performed to observe the formation of autophagosomes, and immunofluorescence, western blot and co‑immunoprecipitation were used to examine the expression of autophagy‑associated proteins and HMGB1. Enzyme‑linked immunosorbent assay analysis was conducted to examine the level of HMGB1 in cell supernatants. Additionally, PC12 cells were treated with RAP to examine the effect of autophagy on HMGB1 release, and the effect of recombinant human HMGB1 and Beclin1 small interfering RNA on autophagy was investigated. The present study confirmed that IPOC inhibited autophagy and HMGB1 secretion, autophagy inhibition induced a decrease in HMGB1 secretion, and HMGB1 secretion attenuation caused autophagy inhibition in return, as demonstrated by immunofluorescence and western blot analyses. Autophagy inhibition and HMGB1 secretion attenuation were, therefore, demonstrated to form a feedback loop under IPOC. These mechanisms illustrated the protective effects of IPOC and may accelerate the clinical use of IPOC.

  10. Cerebral Palsy (CP) Quiz

    MedlinePlus

    ... Submit Button Past Emails CDC Features Pop Quiz: Cerebral Palsy Language: English Español (Spanish) Recommend on Facebook Tweet ... Sandy is the parent of a child with cerebral palsy and the Board President of Gio’s Garden , a ...

  11. Current management and treatment of cerebral vasospasm complicating SAH.

    PubMed

    Kühn, Anna Luisa; Balami, Joyce Saleh; Grunwald, Iris Quasar

    2013-03-01

    Cerebral vasospasm is a common and serious complication of aneurysmal subarachnoid haemorrhage. Despite the improvements in treatment of aneurysmal subarachnoid haemorrhage (aSAH), cerebral vasospasm complicating aSAH has remained the main cause of morbidity and mortality. Subarachnoid haemorrhage (SAH)-induced vasospasm is a complex entity caused by vasculopathy, impaired autoregulation, and hypovolaemia, causing a regional reduction of cerebral brain perfusion which can then induce ischaemia. Cerebral vasospasm can present either asymptomatically detected only radiologically or symptomatically (delayed ischaemic neurologic deficit). The various diagnostic approaches include the use of transcranial doppler, digital subtraction angiography and multimodal computed tomography (CT) and magnetic resonance (MR) techniques. Although digital subtraction angiography is usually the gold standard for the diagnosis of cerebral vasospam, transcranial doppler is commonly the first-screening method for the detection of cerebral vasospam. The treatment of subarachnoid haemorrhage -induced vasospasm include the use of both medical and endovascular therapy. The aim of this review is to discuss the various current therapeutic options and future perspective measures for reducing cerebral vasospasm induced stroke after SAH.

  12. l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

    PubMed

    Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

    2017-01-01

    We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose.

  13. Amelioration by black tea of sodium fluoride-induced changes in protein content of cerebral hemisphere, cerebellum and medulla oblongata in brain region of mice.

    PubMed

    Trivedi, Mrugesh H; Verma, Ramtej J; Chinoy, Niloufer J

    2007-01-01

    Oral administration of sodium fluoride (NaF, 6 and 12 mg/kg body weight/day) to Swiss strain male albino mice for 30 days caused significant dose-dependant reduction in the content of acidic, basic, neutral, and total protein in cerebral hemisphere, cerebellum and medulla oblongata region of brain. After 30 days of NaF treatment, followed by withdrawal of treatment for 30 days, partial but significant amelioration occurred. Administration of 2% black tea extract alone for 30 days did not cause any significant effect. However, concurrent administration of NaF and black tea extract for 30 days caused significant amelioration in all parameters studied.

  14. Hyperforin attenuates brain damage induced by transient middle cerebral artery occlusion (MCAO) in rats via inhibition of TRPC6 channels degradation.

    PubMed

    Lin, Yun; Zhang, Jian-Cheng; Fu, Jun; Chen, Fang; Wang, Jie; Wu, Zhi-Lin; Yuan, Shi-Ying

    2013-02-01

    Hyperforin, a lipophilic constituent of medicinal herb St John's wort, has been identified as the main active ingredient of St John's wort extract for antidepressant action by experimental and clinical studies. Hyperforin is currently known to activate transient receptor potential canonical (subtype) 6 (TRPC6) channel, increase the phosphorylated CREB (p-CREB), and has N-methyl-D-aspartate receptor-antagonistic effect that convert potential neuroprotective effects in vitro. However, the protective effects of hyperforin on ischemic stroke in vivo remain controversial and its neuroprotective mechanisms are still unclear. This study was designed to examine the effects of intracerebroventricular (i.c.v.) injection of hyperforin on transient focal cerebral ischemia in rats. Hyperforin, when applied immediately after middle cerebral artery occlusion (MCAO) onset, significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores at 24 hours after reperfusion accompanied by elevated TRPC6 and p-CREB activity and decreased SBDP145 activity. When MEK or CaMKIV activity was specifically inhibited, the neuroprotective effect of hyperforin was attenuated, and we observed a correlated decrease in CREB activity. In conclusion, our results clearly showed that i.c.v. injection of hyperforin immediately after MCAO onset blocked calpain-mediated TRPC6 channels degradation, and then to stimulate the Ras/MEK/ERK and CaMKIV pathways that converge on CREB activation, contributed to neuroprotection.

  15. Diagnosis, treatment, and prevention of cerebral palsy.

    PubMed

    O'Shea, Thomas Michael

    2008-12-01

    Cerebral palsy is the most prevalent cause of persisting motor function impairment with a frequency of about 1/500 births. In developed countries, the prevalence rose after introduction of neonatal intensive care, but in the past decade, this trend has reversed. A recent international workshop defined cerebral palsy as "a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain." In a majority of cases, the predominant motor abnormality is spasticity; other forms of cerebral palsy include dyskinetic (dystonia or choreo-athetosis) and ataxic cerebral palsy. In preterm infants, about one-half of the cases have neuroimaging abnormalities, such as echolucency in the periventricular white matter or ventricular enlargement on cranial ultrasound. Among children born at or near term, about two-thirds have neuroimaging abnormalities, including focal infarction, brain malformations, and periventricular leukomalacia. In addition to the motor impairment, individuals with cerebral palsy may have sensory impairments, cognitive impairment, and epilepsy. Ambulation status, intelligence quotient, quality of speech, and hand function together are predictive of employment status. Mortality risk increases incrementally with increasing number of impairments, including intellectual, limb function, hearing, and vision. The care of individuals with cerebral palsy should include the provision of a primary care medical home for care coordination and support; diagnostic evaluations to identify brain abnormalities, severity of neurologic and functional abnormalities, and associated impairments; management of spasticity; and care for associated problems such as nutritional deficiencies, pain, dental care, bowel and bladder continence, and orthopedic complications. Current strategies to decrease the risk of cerebral palsy include interventions to

  16. Effects of desflurane on cerebral autoregulation.

    PubMed

    Bedforth, N M; Girling, K J; Skinner, H J; Mahajan, R P

    2001-08-01

    The aim of this study was to determine the effects of desflurane, at 1 and 1.5 MAC, on cerebral autoregulation. Data were analysed from eight patients undergoing non-neurosurgical procedure. The blood flow velocity in the middle cerebral artery was measured by transcranial Doppler ultrasound and cerebral autoregulation was assessed by the transient hyperaemic response test. Partial pressure of the end-tidal carbon dioxide (PE'(CO(2))) and mean arterial pressure were measured throughout the study. Anaesthesia was induced with propofol and was maintained with desflurane at end-tidal concentrations of 7.4% (1 MAC) or 10.8% (1.5 MAC). The order of administration of the desflurane concentrations was determined randomly and a period of 15 min was allowed for equilibration at each concentration. The transient hyperaemic response tests were performed before induction of anaesthesia and after equilibration with each concentration of desflurane. An infusion of phenylephrine was used to maintain pre-induction mean arterial pressure and ventilation was adjusted to maintain the pre-induction value of PE'(CO(2)) throughout the study. Two indices derived from the transient hyperaemic response test (the transient hyperaemic response ratio and the strength of autoregulation) were used to assess cerebral autoregulation. Desflurane resulted in a marked and significant impairment in cerebral autoregulation; at concentrations of 1.5 MAC, autoregulation was almost abolished.

  17. CXCR-7 receptor promotes SDF-1α-induced migration of bone marrow mesenchymal stem cells in the transient cerebral ischemia/reperfusion rat hippocampus.

    PubMed

    Wang, Yulan; Fu, Wei; Zhang, Shichun; He, Xiaomei; Liu, Zhi'an; Gao, Diansuai; Xu, Tiejun

    2014-08-05

    The stromal cell-derived factor 1/C-X-C chemokine receptor type 4 (SDF-1/CXCR-4) axis plays an important role during stem cell recruitment. SDF-1 can also bind the more recently described CXCR-7 receptor, but effects of SDF-1/CXCR-7 signaling on stem cell migrating to ischemic brain injury area are little known. In the present study, we investigated the effect of CXCR-7 on bone marrow mesenchymal stem cell (BMSC) migration toward SDF-1α in the cerebral ischemia/reperfusion (I/R) rat hippocampus. We cultured BMSCs from rats and characterized them using flow cytometry, immunocytochemistry, western blotting, and immunofluorescence to detect SDF-1α, CXCR-4, and CXCR-7 expression in third passage BMSCs (P3-BMSCs). We also prepared the model of transient cerebral I/R by four-vessel occlusion (4-VO), and BMSCs were transplanted into I/R rat brain via lateral ventricle (LV) injection (20μl, 1×10(6)/ml). After that, we examined the effect of BMSCs migration in the cerebral I/R rat hippocampus through Transwell chamber assay. Our results show that SDF-1α, CXCR-4, and CXCR-7 were expressed in P3-BMSCs. Moreover, SDF-1α expression was increased in I/R hippocampus. At 48h after transplant, green fluorescent BrdU-BMSCs were observed in transplant groups, but no green fluorescent BrdU-BMSCs were seen in medium group. Among BMSCs transplant groups, the number of BrdU-BMSCs positive cell was the highest in BMSC group. Treatment with AMD3100 and/or CXCR-7 neutralizing antibody decreased the number of BMSC migration. Collectively, these findings indicate that CXCR-4 and -7 receptors were co-expressed in BMSCs and synergistically promoted BMSC migration. The effect of CXCR-7 was stronger than that of CXCR-4. Moreover, BMSCs that migrated to hippocampus promoted the autocrine and paracrine signaling of SDF-1α.

  18. Cerebral Palsy (For Parents)

    MedlinePlus

    ... palsy — causes a problem with balance and depth perception Since cerebral palsy affects muscle control and coordination, ... fluid into the lungs) gastroesophageal reflux (spitting up) speech problems drooling tooth decay sleep disorders osteoporosis (weak, ...

  19. Cerebral Contusions and Lacerations

    MedlinePlus

    ... Sports-Related Concussion Diffuse Axonal Injury Intracranial Hematomas Skull Fracture Cerebral contusions are bruises of the brain, ... object or pushed-in bone fragment from a skull fracture. Motor vehicle crashes and blows to the ...

  20. Cerebral amyloid angiopathy

    MedlinePlus

    ... 911) if you have sudden loss of movement , sensation, vision, or speech. Alternative Names Amyloidosis - cerebral; CAA; Congophilic angiopathy Images Amyloidosis on the fingers Arteries of the brain References Kase CS, Shoamanesh A. Intracerebral hemorrhage. In: Daroff ...

  1. Nanomedicine in cerebral palsy.

    PubMed

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed.

  2. Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenous estrogen-induced neuroprotection against transient global cerebral ischemia by a non-genomic mechanism in male rats.

    PubMed

    Wang, Ran; Zhang, Quan-Guang; Han, Dong; Xu, Jing; Lü, Qian; Zhang, Guang-Yi

    2006-12-01

    Numerous studies have demonstrated the neuroprotective effects of estrogen in experimental cerebral ischemia. To investigate molecular mechanisms of estrogen neuroprotection in global ischemia, immunoblotting, immunohistochemistry and Nissel-staining analysis were used. Our results showed that chronic pretreatment with beta-estradiol 3-benzoate (E2) enhanced Akt1 activation and reduced the activation of mixed-lineage kinase 3 (MLK3), mitogen-activated protein kinase kinase 4/7 (MKK4/7), and c-Jun N-terminal kinase 1/2 (JNK1/2) in the hippocampal CA1 subfield during reperfusion after 15 min of global ischemia. In addition, E2 reduced downstream JNK nuclear and non-nuclear components, c-Jun and Bcl-2 phosphorylation and Fas ligand protein expression induced by ischemia/reperfusion. Administration of phosphoinositide 3-kinase (PI3K) inhibitor LY 294,002 prevented both activation of Akt1 and inhibition of MLK3, MKK4/7 and JNK1/2. The interaction between ERalpha and the p85 subunit of PI3K was also examined. E2 and antiestrogen ICI 182,780 promoted and prevented this interaction, respectively. Furthermore, ICI 182,780 blocked both the activation of Akt1 and the inhibition of MLK3, MKK4/7 and JNK1/2. Photomicrographs of cresyl violet-stained brain sections showed that E2 reduced CA1 neuron loss after 5 days of reperfusion, which was abolished by ICI 182,780 and LY 294,002. Our data indicate that in response to estrogen, ERalpha interacts with PI3K to activate Akt1, which may inhibit the MLK3-MKK4/7-JNK1/2 pathway to protect hippocampal CA1 neurons against global cerebral ischemia in male rats.

  3. Deletion of C-reactive protein ameliorates experimental cerebral malaria?

    PubMed Central

    Szalai, Alexander J.; Barnum, Scott R.; Ramos, Theresa N.

    2014-01-01

    Background C-reactive protein (CRP) level correlates with parasitemia and severity of malaria, but whether this reflects causality remains unknown. Methods Using CRP-transgenic and CRP-deficient mice we compared the onset and severity of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA). Results CRP-deficient mice were most resistant to ECM. Conclusions CRP might contribute to the development of cerebral malaria, rather than protect against it. PMID:25002461

  4. Alcohols induce rapid depletion of intracellular free Mg2+ in cerebral vascular muscle cells: relation to chain length and partition coefficient.

    PubMed

    Altura, B M; Zhang, A; Cheng, T P; Altura, B T

    1995-01-01

    Acute effects of a series of alcohols (methanol, ethanol, n-butanol) on intracellular free magnesium concentration ([Mg2+]i) in canine cerebral vascular smooth muscle cells was studied using mag-fura-2 and digital imaging microscopy. In 1.2 mM [Mg2+]o, basal [Mg2+]i was 500 +/- 30 microM. Exposure of cells to a low concentration (25 mM) of ethanol, but not methanol, for only 30 s resulted in significant loss of [Mg2+]i. Exposure to 100 mM methanol, ethanol, and butanol for 30 s resulted in a relative order of potency for [Mg2+]i depletion, where butanol > ethanol > methanol. The heterogeneous and relative subcellular compartmented concentrations of [Mg2+]i, where perinuclear > nuclear > peripheral (cytosolic) region, was not significantly altered by the alcohols. The degree of cellular depletion of [Mg2+]i was directly a function of each alcohol's partition coefficient and chain length. The latter is suggestive of the probability that alcohols promote intracellular depletion of Mg2+ by partitioning in membranes and disordering lipid bilayers.

  5. The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia.

    PubMed

    Ostrowski, Robert P; Graupner, Gerhart; Titova, Elena; Zhang, Jennifer; Chiu, Jeffrey; Dach, Neal; Corleone, Dalia; Tang, Jiping; Zhang, John H

    2008-01-01

    We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.

  6. An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malaria.

    PubMed

    Bongfen, Silayuv E; Rodrigue-Gervais, Ian-Gael; Berghout, Joanne; Torre, Sabrina; Cingolani, Pablo; Wiltshire, Sean A; Leiva-Torres, Gabriel A; Letourneau, Louis; Sladek, Robert; Blanchette, Mathieu; Lathrop, Mark; Behr, Marcel A; Gruenheid, Samantha; Vidal, Silvia M; Saleh, Maya; Gros, Philippe

    2012-01-01

    Cerebral malaria (CM) is a lethal neurological complication of malaria. We implemented a genome-wide screen in mutagenized mice to identify host proteins involved in CM pathogenesis and whose inhibition may be of therapeutic value. One pedigree (P48) segregated a resistance trait whose CM-protective effect was fully penetrant, mapped to chromosome 8, and identified by genome sequencing as homozygosity for a mis-sense mutation (W81R) in the FERM domain of Janus-associated kinase 3 (Jak3). The causative effect of Jak3(W81R) was verified by complementation testing in Jak3(W81R/-) double heterozygotes that were fully protected against CM. Jak3(W81R) homozygotes showed defects in thymic development with depletion of CD8(+) T cell, B cell, and NK cell compartments, and defective T cell-dependent production of IFN-γ. Adoptive transfer of normal splenocytes abrogates CM resistance in Jak3(W81R) homozygotes, an effect attributed to the CD8(+) T cells. Jak3(W81R) behaves as a dominant negative variant, with significant CM resistance of Jak3(W81R/+) heterozygotes, compared to CM-susceptible Jak3(+/+) and Jak3(+/-) controls. CM resistance in Jak3(W81R/+) heterozygotes occurs in presence of normal T, B and NK cell numbers. These findings highlight the pathological role of CD8(+) T cells and Jak3-dependent IFN-γ-mediated Th1 responses in CM pathogenesis.

  7. Hypernatraemia in cerebral disorders

    PubMed Central

    Taylor, W. H.

    1962-01-01

    Six patients are described in whom cerebral damage was associated with raised plasma sodium and chloride concentrations and with extremely low urinary outputs of sodium and chloride. The patients were not clinically dehydrated and direct determinations showed that the blood and plasma volumes, the endogenous creatinine clearance, and the urinary output of antidiuretic hormone were normal. For these and other reasons it is concluded that the metabolic picture results not from diminished circulatory volume, water deficiency, sodium deficiency, undetected diabetes insipidus or osmotic diuresis, but from the cerebral damage itself. In these and other cited cases, the cerebral damage was localized chiefly in the frontal lobes, hypothalamus or lower brain-stem, thus suggesting a descending pathway, the relationship of which to the pineal area controlling aldosterone secretion requires clarification. Images PMID:13920001

  8. Duplicated middle cerebral artery.

    PubMed

    Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

    2009-01-01

    Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion.

  9. Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model.

    PubMed

    Yoshiyama, Yasumasa; Uryu, Kunihiro; Higuchi, Makoto; Longhi, Luca; Hoover, Rachel; Fujimoto, Scott; McIntosh, Tracy; Lee, Virginia M-Y; Trojanowski, John Q

    2005-10-01

    Traumatic brain injury (TBI) is a risk factors for Alzheimer's disease (AD), and repetitive TBI (rTBI) may culminate in dementia pugilistica (DP), a syndrome characterized by progressive dementia, parkinsonism, and the hallmark brain lesions of AD, including neurofibrillary tangles (NFTs), formed by abnormal tau filaments and senile plaques (SPs) composed of Abeta fibrils. Previous study showed that mild rTBI (mrTBI) accelerated the deposition of Abeta in the brains of transgenic (Tg) mice (Tg2576) that over-express human Abeta precursor proteins with the familial AD Swedish mutations (APP695swe) and model of AD-like amyloidosis. Here, we report studies of the effects of mrTBI on AD-like tau pathologies in Tg mice expressing the shortest human tau isoform (T44) subjected to mrTBI, causing brain concussion without structural brain damage to simulate injuries linked to DP. Twelve-month-old Tg T44 (n = 18) and wild-type (WT; n = 24) mice were subjected to mrTBI (four times a day, 1 day per week, for 4 weeks; n = 24) or sham treatment (n = 18). Histopathological analysis of mice at 9 months after mrTBI revealed that one of the Tg T44 mice showed extensive telencephalic NFT and cerebral atrophy. Although statistical analysis of neurobehavioral tests at 6 months after mrTBI did not show any significant difference in any of groups of mice, the Tg T44 mouse with extensive NFT had an exceptionally low neurobehavioral score. The reasons for the augmentation of tau pathologies in only one T44 tau Tg mouse subjected to mrTBI remain to be elucidated.

  10. Neuronal damage in hippocampal subregions induced by various durations of transient cerebral ischemia in gerbils using Fluoro-Jade B histofluorescence.

    PubMed

    Yu, Dong-Kun; Yoo, Ki-Yeon; Shin, Bich Na; Kim, In Hye; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon; Cho, Yong-Jun; Kang, Il-Jun; Kim, Young-Myeong; Won, Moo-Ho

    2012-02-09

    Although there are many studies on ischemic brain damage in the gerbil, which is a good model of transient cerebral ischemia, studies on neuronal damage according to the duration of ischemia-reperfusion (I-R) time are limited. We carried out neuronal damage in the gerbil hippocampus after various durations of I-R (5, 10, 15 and 20 min) using Fluoro-Jade B (F-J B, a maker for neuronal degeneration) histofluorescence as well as cresyl violet (CV) staining. The changes of CV positive ((+)) neurons were well detected in the hippocampal CA1 region, not in the other regions. F-J B histofluorescence staining showed apparent neuronal damage in all the hippocampal subregions. In the CA1, most of the pyramidal neurons of the stratum pyramidale (SP) were stained with F-J B (about 100/mm(2) in a section), and F-J B(+) neurons in the other ischemia-groups were not changed. In the CA2, a few F-J B(+) neurons were detected in the SP of the 5 min ischemia-group, and F-J B(+) neurons were gradually increased with the longer time of ischemia: in the 20 min ischemia-group, the mean number of F-J B(+) neurons was about 85/mm(2) in a section. In the CA3, some F-J B(+) neurons were observed only in the SP of the 20 min ischemia-group. In the dentate gyrus, some F-J B positive neurons were detected only in the polymorphic layer (PL) of the 5 min ischemia-group, and the number of F-J B(+) neurons were gradually increased with the longer ischemic time. Our findings indicate that F-J B histofluorescence showed a very high quality of neuronal damage in all the hippocampal subregions.

  11. Cerebral vasospasm pharmacological treatment: an update.

    PubMed

    Siasios, Ioannis; Kapsalaki, Eftychia Z; Fountas, Kostas N

    2013-01-01

    Aneurysmal subarachnoid hemorrhage- (aSAH-) associated vasospasm constitutes a clinicopathological entity, in which reversible vasculopathy, impaired autoregulatory function, and hypovolemia take place, and lead to the reduction of cerebral perfusion and finally ischemia. Cerebral vasospasm begins most often on the third day after the ictal event and reaches the maximum on the 5th-7th postictal days. Several therapeutic modalities have been employed for preventing or reversing cerebral vasospasm. Triple "H" therapy, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators, administration of substances like magnesium sulfate, statins, fasudil hydrochloride, erythropoietin, endothelin-1 antagonists, nitric oxide progenitors, and sildenafil, are some of the therapeutic protocols, which are currently employed for managing patients with aSAH. Intense pathophysiological mechanism research has led to the identification of various mediators of cerebral vasospasm, such as endothelium-derived, vascular smooth muscle-derived, proinflammatory mediators, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Oral, intravenous, or intra-arterial administration of antagonists of these mediators has been suggested for treating patients suffering a-SAH vasospam. In our current study, we attempt to summate all the available pharmacological treatment modalities for managing vasospasm.

  12. Cerebral Vasospasm Pharmacological Treatment: An Update

    PubMed Central

    Siasios, Ioannis; Kapsalaki, Eftychia Z.; Fountas, Kostas N.

    2013-01-01

    Aneurysmal subarachnoid hemorrhage- (aSAH-) associated vasospasm constitutes a clinicopathological entity, in which reversible vasculopathy, impaired autoregulatory function, and hypovolemia take place, and lead to the reduction of cerebral perfusion and finally ischemia. Cerebral vasospasm begins most often on the third day after the ictal event and reaches the maximum on the 5th–7th postictal days. Several therapeutic modalities have been employed for preventing or reversing cerebral vasospasm. Triple “H” therapy, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators, administration of substances like magnesium sulfate, statins, fasudil hydrochloride, erythropoietin, endothelin-1 antagonists, nitric oxide progenitors, and sildenafil, are some of the therapeutic protocols, which are currently employed for managing patients with aSAH. Intense pathophysiological mechanism research has led to the identification of various mediators of cerebral vasospasm, such as endothelium-derived, vascular smooth muscle-derived, proinflammatory mediators, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Oral, intravenous, or intra-arterial administration of antagonists of these mediators has been suggested for treating patients suffering a-SAH vasospam. In our current study, we attempt to summate all the available pharmacological treatment modalities for managing vasospasm. PMID:23431440

  13. Postradiation regional cerebral blood flow in primates

    SciTech Connect

    Cockerham, L.G.; Cerveny, T.J.; Hampton, J.D.

    1986-06-01

    Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with hypotension and a dramatic release of mast cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomenon and the postradiation decrease in cerebral blood flow, primates were exposed to 100 Gy (1 Gy = 100 rads), whole-body, gamma radiation. Pontine and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. Systemic arterial histamine levels were determined preradiation and postradiation. Data obtained indicated that radiated animals showed a decrease in blood flow of 63% in the motor cortex and 51% in the pons by 10 min postradiation. Regional cerebral blood flow of radiated animals showed a slight recovery 20 min postradiation, followed by a fall to the 10 min nadir by 60 min postradiation. Immediately, postradiation systemic blood pressure fell 67% and remained at that level for the remainder of the experiment. Histamine levels in the radiated animals increased a hundredfold 2 min postradiation. This study indicates that regional cerebral blood flow decreases postradiation with the development of hypotension and may be associated temporally with the postradiation release of histamine.

  14. Astrocyte regulation of cerebral vascular tone

    PubMed Central

    Iddings, Jennifer A.

    2013-01-01

    Cerebral blood flow is controlled by two crucial processes, cerebral autoregulation (CA) and neurovascular coupling (NVC) or functional hyperemia. Whereas CA ensures constant blood flow over a wide range of systemic pressures, NVC ensures rapid spatial and temporal increases in cerebral blood flow in response to neuronal activation. The focus of this review is to discuss the cellular mechanisms by which astrocytes contribute to the regulation of vascular tone in terms of their participation in NVC and, to a lesser extent, CA. We discuss evidence for the various signaling modalities by which astrocytic activation leads to vasodilation and vasoconstriction of parenchymal arterioles. Moreover, we provide a rationale for the contribution of astrocytes to pressure-induced increases in vascular tone via the vasoconstrictor 20-HETE (a downstream metabolite of arachidonic acid). Along these lines, we highlight the importance of the transient receptor potential channel of the vanilloid family (TRPV4) as a key molecular determinant in the regulation of vascular tone in cerebral arterioles. Finally, we discuss current advances in the technical tools available to study NVC mechanisms in the brain as it relates to the participation of astrocytes. PMID:23792684

  15. Cerebral Folate Deficiency

    ERIC Educational Resources Information Center

    Gordon, Neil

    2009-01-01

    Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

  16. United Cerebral Palsy

    MedlinePlus

    ... be sure to follow us on Twitter ! Affiliate Network UCP affiliates provide services and support on a community-by-community basis, serving the unique needs of people with disabilities in their region. Find your ... and their networks. Individuals with cerebral palsy and other disabilities deserve ...

  17. Cerebral Palsy (For Teens)

    MedlinePlus

    ... brain is affected and which parts of the body that section of the brain controls. If CP affects both arms and both legs, ... the case of spastic CP) or to help control seizures. And some might have special surgeries to keep their arms or legs straighter and more ... Coping With Cerebral Palsy Puberty can ...

  18. Cerebral Palsy Litigation

    PubMed Central

    Sartwelle, Thomas P.

    2015-01-01

    The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

  19. N-Nitrosodiethylamine-Induced Pig Liver Hepatocellular Carcinoma Model: Radiological and Histopathological Studies

    SciTech Connect

    Li Xiao; Zhou Xiangping Guan Yongsong; Wang, Yi-Xiang J.; Scutt, Diane; Gong Qiyong

    2006-06-15

    Experimental research involving animal models plays a critical role in the development and improvement of minimally invasive therapies for hepatocellular carcinoma (HCC). As a large animal, the pig is commonly used for surgery and interventional radiology research. In this study, liver multicentric HCC with cirrhosis was induced in six China Taihu pigs by intraperitoneal injection of 10 mg/kg of N-nitrosodiethylamine once a week for 3 months, followed by a period of 10-12 months without N-nitrosodiethylamine treatment. All pigs were in generally good health until the end of the study. The tumor nodules appeared hyperattenuating in the arterial phase of a dynamic computed tomography (CT) scan. Digital subtraction angiography (DSA) and CT angiography demonstrated that the tumors derived their blood supply mainly from the hepatic artery system. Lipiodol-CT showed Lipiodol retention in tumor areas. The histology and electron microscopic ultrastructure of the chemically induced liver HCC in this study resembled human HCC with a cirrhosis background. An immunohistochemistry study confirmed that the tumors were of hepatocyte origin. All highly, moderately, and poorly differentiated HCC tumors were identified in this study. Cholangiocarcinoma was not seen in any of the animals. Due to its comparable size to human anatomy, the pig liver HCC model would give a better scope for interventional and surgical manipulations than small animal models.

  20. Neuroprotection by Alpha 2-Adrenergic Agonists in Cerebral Ischemia

    PubMed Central

    Zhang, Yonghua; Kimelberg, Harold K.

    2005-01-01

    Ischemic brain injury is implicated in the pathophysiology of stroke and brain trauma, which are among the top killers worldwide, and intensive studies have been performed to reduce neural cell death after cerebral ischemia. Alpha 2-adrenergic agonists have been shown to improve the histomorphological and neurological outcome after cerebral ischemic injury when administered during ischemia, and recent studies have provided considerable evidence that alpha 2-adrenergic agonists can protect the brain from ischemia/reperfusion injury. Thus, alpha 2-adrenergic agonists are promising potential drugs in preventing cerebral ischemic injury, but the mechanisms by which alpha 2-adrenergic agonists exert their neuroprotective effect are unclear. Activation of both the alpha 2-adrenergic receptor and imidazoline receptor may be involved. This mini review examines the recent progress in alpha 2-adrenergic agonists - induced neuroprotection and its proposed mechanisms in cerebral ischemic injury. PMID:18369397

  1. [Raman spectra of monkey cerebral cortex tissue].

    PubMed

    Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

    2010-01-01

    Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

  2. Cerebral blood flow and metabolism during sleep.

    PubMed

    Madsen, P L; Vorstrup, S

    1991-01-01

    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different levels of sleep into consideration, show that light sleep (stage II) is characterized by global levels of CBF and CMR only slightly reduced by 3-10% below the level associated with wakefulness, whereas CBF and CMR during deep sleep (stage III-IV) is dramatically reduced by 25-44%. Furthermore, recent data indicate that global levels of CBF and CMR are about the same during REM sleep as in wakefulness. On the regional level, deep sleep seems to be associated with a uniform decrease in regional CBF and CMR. Investigations concerning regional CBF and CMR during REM sleep are few but data from recent investigations seem to identify site-specific changes in regional CBF and CMR during REM sleep. CBF and CMR are reflections of cerebral synaptic activity and the magnitude of reduction in these variables associated with deep sleep indicates that overall cerebral synaptic activity is reduced to approximately one-half the level associated with wakefulness, while cerebral synaptic activity levels during REM sleep are similar to wakefulness. However, even though the new understanding of CBF and CMR during sleep provides significant and important information of the brain's mode of working during sleep, it does not at its current state identify the physiological processes involved in sleep or the physiological role of sleep.

  3. Deletion of TRPC6 Attenuates NMDA Receptor-Mediated Ca2+ Entry and Ca2+-Induced Neurotoxicity Following Cerebral Ischemia and Oxygen-Glucose Deprivation

    PubMed Central

    Chen, Jin; Li, Zhaozhong; Hatcher, Jeffery T.; Chen, Qing-Hui; Chen, Li; Wurster, Robert D.; Chan, Sic L.; Cheng, Zixi

    2017-01-01

    Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na+ and Ca2+ and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca2+ levels ([Ca2+]i), we found that OGD induced a significant higher increase in glutamate-evoked Ca2+ influx compared to untreated control and such an increase was reduced by TRPC6 deletion. Enhancement of TRPC6 expression using AdCMV-TRPC6-GFP infection in WT neurons increased [Ca2+]i in response to glutamate application compared to AdCMV-GFP control. Inhibition of N-methyl-d-aspartic acid receptor (NMDAR) with MK801 decreased TRPC6-dependent increase of [Ca2+]i in TRPC6 infected cells, indicating that such a Ca2+ influx was NMDAR dependent. Furthermore, TRPC6-dependent Ca2+ influx was blunted by blockade of Na+ entry in TRPC6 infected cells. Finally, OGD-enhanced Ca2+ influx was reduced, but not completely blocked, in the presence of voltage-dependent Na+ channel blocker tetrodotoxin (TTX) and dl-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) blocker CNQX. Altogether, we concluded that I/R-induced brain damage was, in part, due to upregulation of TRPC6 in cortical neurons. We postulate that overexpression of TRPC6 following I/R may induce neuronal death partially through TRPC6-dependent Na+ entry which activated NMDAR, thus leading to a damaging Ca2+ overload. These findings may provide a potential target for future intervention in stroke-induced brain damage.

  4. [Effects of xenon anesthesia on cerebral blood flow in neurosurgical patients without intracranial hypertension].

    PubMed

    Rylova, A V; Beliaev, A Iu; Lubnin, A Iu

    2013-01-01

    Among anesthetic agents used in neurosurgery xenon appears to be the most advantageous. It preserves arterial blood pressure, assures rapid recovery and neuroprotection. But the data is lacking on xenon effect upon cerebral blood flow under anesthetic conditions. We measured flow velocity in middle cerebral artery in neurosurgical patients without intracranial hypertension during closed circuit xenon anesthesia comparing propofol and xenon effect in the same patients. In our study xenon didn't seem to induce clinically relevant changes in cerebral blood flow and preserved cerebral vascular reactivity thus proving its safety in patients without intracranial hypertension.

  5. Magnetic resonance imaging of experimental cerebral oedema.

    PubMed Central

    Barnes, D; McDonald, W I; Tofts, P S; Johnson, G; Landon, D N

    1986-01-01

    Triethyl tin(TET)-induced cerebral oedema has been studied in cats by magnetic resonance imaging (MRI), and the findings correlated with the histology and fine structure of the cerebrum following perfusion-fixation. MRI is a sensitive technique for detecting cerebral oedema, and the distribution and severity of the changes correlate closely with the morphological abnormalities. The relaxation times, T1 and T2 increase progressively as the oedema develops, and the proportional increase in T2 is approximately twice that in T1. Analysis of the magnetisation decay curves reveals slowly-relaxing and rapidly-relaxing components which probably correspond to oedema fluid and intracellular water respectively. The image appearances taken in conjunction with relaxation data provide a basis for determining the nature of the oedema in vivo. Images PMID:3806109

  6. Cerebral glucose consumption following verbal auditory stimulation.

    PubMed

    Kushner, M J; Schwartz, R; Alavi, A; Dann, R; Rosen, M; Silver, F; Reivich, M

    1987-04-14

    We studied the effect of auditory stimulation upon cerebral glucose metabolism in young normals. The stimulus consisted of a non-English discourse which was presented monaurally to 10 normal blindfolded subjects (5 left ear, 5 right); the opposite ear was plugged. Six subjects studied blindfolded and with ears plugged served as controls. Sixteen discrete homologous cortical and subcortical regions of interest were examined. Regional glucose consumption and side-to-side differences in glucose metabolism were analyzed. Monaural stimulation produced significant increases in temporal metabolism contralateral to the side of stimulation. Significant asymmetries in metabolism were found at the temporoparietal junction, inferior parietal region, insula and corpus collosum. The left frontal speech areas remained unaffected. These findings demonstrate that in man the primary auditory pathways retain a contralateral organization. Further, cerebral activation induced by non-meaningful verbal stimulation is widespread within the left temporal and parietal regions but does not impact upon the frontal speech cortices.

  7. Cerebral Amyloid Angiopathy: Emerging Concepts

    PubMed Central

    2015-01-01

    Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis

  8. Managing Malignant Cerebral Infarction

    PubMed Central

    Sahuquillo, Juan; Sheth, Kevin N.; Kahle, Kristopher T.; Walcott, Brian P.

    2011-01-01

    Opinion statement Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death. PMID:21190097

  9. Angiotensin-(1-7) Counteracts Angiotensin II-induced Dysfunction in Cerebral Endothelial Cells via Modulating Nox2/ROS and PI3K/NO Pathways

    PubMed Central

    Xiao, Xiang; Zhang, Cheng; Ma, Xiaotang; Miao, Huilai; Wang, Jinju; Liu, Langni; Chen, Shuzhen; Zeng, Rong; Chen, Yanfang; Bihl, Ji C.

    2015-01-01

    Angiotensin (Ang) II, the main effector of the renin-angiotensin system, has been implicated in the pathogenesis of vascular diseases. Ang-(1-7) binds to the G protein-coupled Mas receptor (MasR) and can exert vasoprotective effects. We investigated the effects and underlying mechanisms of Ang-(1-7) on Ang II-induced dysfunction and oxidative stress in human brain microvascular endothelial cells (HbmECs). The pro-apoptotic activity, reactive oxygen species (ROS) and nitric oxide (NO) productions in HbmECs were measured. The protein expressions of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS) and their phosphorylated forms (p-Akt and p-eNOS) were examined by western blot. MasR antagonist and phosphatidylinositol-3-kinase (PI3K) inhibitor were used for receptor/pathway verification. We found that Ang-(1-7) suppressed Ang II-induced pro-apoptotic activity, ROS over-production and NO reduction in HbmECs, which were abolished by MasR antagonist. In addition, Ang-(1-7) down-regulated the expression of Nox2, and up-regulated the ratios of p-Akt/Akt and its downstream p-eNOS/eNOS in HbmECs. Exposure to PI3K inhibitor partially abrogated Ang-(1-7)-mediated protective effects in HbmECs. Our data suggests that Ang-(1-7)/MasR axis protects HbmECs from Ang II-induced dysfunction and oxidative stress via inhibition of Nox2/ROS and activation of PI3K/NO pathways. PMID:26101159

  10. Angiotensin-(1-7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways.

    PubMed

    Xiao, Xiang; Zhang, Cheng; Ma, Xiaotang; Miao, Huilai; Wang, Jinju; Liu, Langni; Chen, Shuzhen; Zeng, Rong; Chen, Yanfang; Bihl, Ji C

    2015-08-01

    Angiotensin (Ang) II, the main effector of the renin-angiotensin system, has been implicated in the pathogenesis of vascular diseases. Ang-(1-7) binds to the G protein-coupled Mas receptor (MasR) and can exert vasoprotective effects. We investigated the effects and underlying mechanisms of Ang-(1-7) on Ang II-induced dysfunction and oxidative stress in human brain microvascular endothelial cells (HbmECs). The pro-apoptotic activity, reactive oxygen species (ROS) and nitric oxide (NO) productions in HbmECs were measured. The protein expressions of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS) and their phosphorylated forms (p-Akt and p-eNOS) were examined by western blot. MasR antagonist and phosphatidylinositol-3-kinase (PI3K) inhibitor were used for receptor/pathway verification. We found that Ang-(1-7) suppressed Ang II-induced pro-apoptotic activity, ROS over-production and NO reduction in HbmECs, which were abolished by MasR antagonist. In addition, Ang-(1-7) down-regulated the expression of Nox2, and up-regulated the ratios of p-Akt/Akt and its downstream p-eNOS/eNOS in HbmECs. Exposure to PI3K inhibitor partially abrogated Ang-(1-7)-mediated protective effects in HbmECs. Our data suggests that Ang-(1-7)/MasR axis protects HbmECs from Ang II-induced dysfunction and oxidative stress via inhibition of Nox2/ROS and activation of PI3K/NO pathways.

  11. High Altitude Cerebral Edema

    DTIC Science & Technology

    1986-03-01

    English literature and Hultgren et al (3.1) described four more cases of HAPE within the next year. In 1960, Chiodi (5) first reported on a Peruvian...altitude and treatment with steroids and diuretics, CSF pressure was 85 mm H 0. In 1960, Chiodi .(5) described a patient 2 suffering with HACE who...Biol. Chem., 157, 297-302, 1945. 5. Chiodi H: "Mal de montana a forma cerebral; possible mecanismo etiopathogenico," An. Fac. Med. Lima., 43, 437

  12. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia

    PubMed Central

    Zhao, Wanhong; Luo, Chao; Wang, Jue; Gong, Jian; Li, Bin; Gong, Yingxia; Wang, Jun; Wang, Hanqin

    2014-01-01

    3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study ligated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphthalide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits. PMID:25206879

  13. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  14. Regional cerebral blood flow during comprehension and speech (in cerebrally healthy subjects)

    SciTech Connect

    Lechevalier, B.; Petit, M.C.; Eustache, F.; Lambert, J.; Chapon, F.; Viader, F. )

    1989-07-01

    Regional cerebral blood flow (rCBF) was measured by the xenon-133 inhalation method in 10 cerebrally healthy subjects at rest and during linguistic activation tests. These consisted of a comprehension test (binaural listening to a narrative text) and a speech test (making sentences from a list of words presented orally at 30-s intervals). The comprehension task induced a moderate increase in the mean right CBF and in both inferior parietal areas, whereas the speech test resulted in a diffuse increase in the mean CBF of both hemispheres, predominating regionally in both inferior parietal, left operculary, and right upper motor and premotor areas. It is proposed that the activation pattern induced by linguistic stimulation depends on not only specific factors, such as syntactic and semantic aspects of language, but also the contents of the material proposed and the attention required by the test situation.

  15. Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats.

    PubMed

    Chen, Na; Chiu, Po Yee; Ko, Kam Ming

    2008-07-01

    Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to enhance mitochondrial antioxidant status in liver, heart and brain tissues in rodents. Whether or not long-term Sch B treatment can protect against oxidative stress-induced cerebral damage remains unclear. In the present study, the effect of long-term Sch B treatment (1-30 mg/kg/dx15) on cerebral ischemia/reperfusion (I/R) injury was examined in rats. Sch B treatment protected against I/R-induced cerebral damage, as evidenced by the significant increase in the percentage of 2,3,5-triphenyl tetrazolium chloride (TTC)-stained tissues in representative brain slices, when compared with the Sch B-untreated and I/R control. The cerebroprotection was associated with an enhancement in cerebral mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial structural integrity, as assessed by the extents of malondialdehyde production, Ca(2+) loading and cytochrome c release, as well as the sensitivity to Ca(2+)-induced permeability transition, in control and I/R-challenged rats. In conclusion, long-term Sch B treatment could enhance cerebral mitochondrial antioxidant status as well as improve mitochondrial structural integrity, thereby protecting against I/R injury.

  16. Molecular pathophysiology of cerebral edema

    PubMed Central

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

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

  17. Molecular pathophysiology of cerebral edema.

    PubMed

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

    2016-03-01

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

  18. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury

    PubMed Central

    Yan, Chunlin; Zhang, Ji; Wang, Shu; Xue, Guiping; Hou, Yong

    2013-01-01

    Rutaecarpine, an active component of the traditional Chinese medicine Tetradium ruticarpum, has been shown to improve myocardial ischemia reperfusion injury. Because both cardiovascular and cerebrovascular diseases are forms of ischemic vascular disease, they are closely related. We hypothesized that rutaecarpine also has neuroprotective effects on cerebral ischemia reperfusion injury. A cerebral ischemia reperfusion model was established after 84, 252 and 504 μg/kg carpine were given to mice via intraperitoneal injection, daily for 7 days. Results of the step through test, 2,3,5-triphenyl tetrazolium chloride dyeing and oxidative stress indicators showed that rutaecarpine could improve learning and memory ability, neurological symptoms and reduce infarction volume and cerebral water content in mice with cerebral ischemia reperfusion injury. Rutaecarpine could significantly decrease the malondialdehyde content and increase the activities of superoxide dismutase and glutathione peroxidase in mouse brain. Therefore, rutaecarpine could improve neurological function following injury induced by cerebral ischemia reperfusion, and the mechanism of this improvement may be associated with oxidative stress. These results verify that rutaecarpine has neuroprotective effects on cerebral ischemia reperfusion in mice. PMID:25206511

  19. [Intermittent focal cerebral ischemia in hypotension due to pacemaker syndrome].

    PubMed

    Hagendorff, A; Pizzulli, L; Dettmers, C; Block, A; Omran, H; Hartmann, A; Manz, M; Lüderitz, B

    1994-12-01

    A pacemaker syndrome manifested as transient sensoric aphasia in a 68-year-old woman with a VVI-pace-maker implanted after SA-block. The attack occurred during long-term blood pressure recording and Holter monitoring. Borderline hypotension was documented during ventricular pacing which induced a retrograde excitation of the atrium. Clinical investigations excluded any intracranial abnormality, any source of embolism or stenosis of extra- and intracranial cerebral arteries. Cerebral blood flow measurements revealed a significant increase during pacing at elevated heart rate. Therefore, a device for AV-sequential pacing was implanted and basic pacing rate was elevated. The present case report indicates that focal and not only global cerebral ischemia can be produced by an impairment of systemic hemodynamics due to hypotension and a pacemaker syndrome. Improvement of cerebral blood flow during pacing is an unexpected finding contrasting with the concept of autoregulation. In addition, pacemaker implantation should be discussed in patients with transient cerebral perfusion deficits if an improvement of cerebral blood flow is documented along with rising heart rate.

  20. The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine.

    PubMed

    Valvassori, Samira S; Resende, Wilson R; Varela, Roger B; Arent, Camila O; Gava, Fernanda F; Peterle, Bruna R; Dal-Pont, Gustavo C; Carvalho, André F; Andersen, Monica L; Quevedo, João

    2017-02-06

    Studies have suggested the involvement of inflammatory processes in the physiopathology of bipolar disorder. Preclinical evidences have shown that histone deacetylase inhibitors may act as mood-stabilizing agents and protect the brain in models of mania and depression. The aim of the present study was to evaluate the effects of sodium butyrate (SB) and valproate (VPA) on behavioral changes, histone deacetylase activity, and the levels of cytokines in an animal model of mania induced by dextroamphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for a period of 14 days, and then, between the 8th and 14th days, the rats were treated with SB, VPA, or Sal. The activity of histone deacetylase and the levels of cytokines (interleukin (IL) IL-4, IL-6, and IL-10 and tumor necrosis factor-alpha (TNF-α)) were evaluated in the frontal cortex and striatum of the rats. The administration of d-AMPH increased the activity of histone deacetylase in the frontal cortex. Administration of SB or VPA decreased the levels of histone deacetylase activity in the frontal cortex and striatum of rats. SB per se increased the levels of cytokines in both of the brain structures evaluated. AMPH increased the levels of cytokines in both of the brain structures evaluated, and VPA reversed this alteration. The effects of SB on d-AMPH-induced cytokine alterations were dependent on the brain structure and the cytokine evaluated. Despite VPA and SB having a similar mechanism of action, both being histone deacetylase inhibitors, they showed different effects on the levels of cytokines. The present study reinforces the need for more research into histone deacetylase inhibitors being used as a possible target for new medications in the treatment of bipolar disorder.

  1. Correlation between cerebral oxygen metabolism and cerebral blood flow simultaneously measured before and after acetazolamide administration

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hiroichiro; Yamauchi, Hideto; Hazama, Shiro; Hamamoto, Hirotsugu; Inoue, Nobuhiro

    1999-10-01

    The cerebral circulation and metabolism of ten preoperative cardiac surgery patients were assessed. Alterations in regional cerebral blood flow (rCBF), measured by 123I-N- isopropyl-p-iodo-amphetamine single-photon emission computed tomography, and in cerebral oxygen metabolism, simultaneously detected by near-infrared spectroscopy (NIRS) before and after acetazolamide administration, were investigated. The rCBF (ml/min/100 g) increased significantly from 40.21 +/- 7.65 to 56.24 +/- 13.69 (p equals 0.001), and a significant increase in oxyhemoglobin (Oxy-Hb) of 13.9% (p equals 0.0022) and total hemoglobin (Total-Hb) of 5.7% (0.0047) along with a significant decrease in deoxyhemoglobin (Deoxy-Hb) of 8.9% (p equals 0.0414) were observed concomitantly. Thus, the Oxy-Hb/Total- Hb ratio (%Oxy-Hb) rose significantly from 67.26 +/- 9.82% to 72.98 +/- 8.09% (p equals 0.0022). Examination of the relationships between individual parameters showed that the percentage changes in rCBF and Oxy-Hb were significantly correlated (r equals 0.758, p equals 0.011). The percentage changes in rCBF and %Oxy-Hb were also correlated significantly (r equals 0.740, p equals 0.014). In conclusion, this evidence suggested that NIRS is able to detect relative changes in cerebral hemodynamics and reflect luxury perfusion induced by acetazolamide.

  2. Effects of mild traumatic brain injury on immunoreactivity for the inducible transcription factors c-Fos, c-Jun, JunB, and Krox-24 in cerebral regions associated with conditioned fear responding.

    PubMed

    Abrous, D N; Rodriguez, J; le Moal, M; Moser, P C; Barnéoud, P

    1999-05-01

    We have previously demonstrated that mild traumatic brain injury (TBI) of the right parietal cortex results in a relatively selective deficit in conditioned fear responding. However, this behavioural deficit is very consistent and unrelated to the extent of the cortical necrotic lesion. We were therefore interested in determining if other brain regions might show a consistent response to mild TBI, and therefore, more reliably relate to the behavioural change. Increased expression of inducible transcription factors (ITFs) has been used to study which brain regions respond to a variety of events. In the present study, we examined the expression patterns of immunoreactivity (IR) for four ITFs (c-Fos, c-Jun, JunB, and Krox-24) at 3 h after mild fluid percussion TBI. Changes in ITF expression were only observed ipsilateral to the side of TBI. The clearest changes were observed in brain regions known to be involved in conditioned fear responding, such as the amygdala complex and hippocampal formation and several cortical regions. In contrast, no changes in IR for any of the ITFs were observed in the striatum, nucleus accumbens, nucleus basalis magnocellularis, septum or periacqueductal grey. Unlike the extent of visible damage to the cortex at the site of impact, the overexpression of ITFs showed a notable consistency between animals subjected to TBI. This consistency in regions known to be involved in conditioned fear responding (i.e., amygdala complex and hippocampal formation) lead us to suggest that it is these changes, rather than the more variable cortical necrotic lesion, that is responsible for the behavioural deficits we observe following mild TBI. Importantly, our results demonstrate that like the hippocampus, the amygdala is a sub-cortical structure particularly sensitive to the effects of mild brain trauma and underline the fact that cerebral regions distant from the location of the fluid impact can be affected.

  3. Generation of improved human cerebral organoids from single copy DYRK1A knockout induced pluripotent stem cells in trisomy 21: hypothetical solutions for neurodevelopmental models and therapeutic alternatives in down syndrome.

    PubMed

    Çağlayan, E Sacide

    2016-12-01

    Dual-specificity thyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a strong therapeutic target to ameliorate cognitive functions of Down Syndrome (DS). Genetic normalization of Dyrk1a is sufficient to normalize early cortical developmental phenotypes in DS mouse models. Gyrencephalic human neocortical development is more complex than that in lissencephalic mice; hence, cerebral organoids (COs) can be used to model early neurodevelopmental defects of DS. Single copy DYRK1A knockout COs (scDYRK1AKO-COs) can be generated from manipulated DS derived (DS-) induced pluripotent stem cells (iPSCs) and genetic normalization of DYRK1A is expected to result in corrected neurodevelopmental phenotypes that can be reminiscent of normal COs. DYRK1A knock-in (DYRK1AKI) COs can be derived after genetic manipulations of normal iPSCs and would be valuable to evaluate impaired neocortical development as can be seen in DS-COs. DYRK1A mutations cause severe human primary microcephaly; hence, dose optimization studies of DYRK1A inhibitors will be critical for prenatal therapeutic applications in DS. Several doses of DYRK1A inhibitors can be tested in the neurodevelopment process of DS-COs and DS-scDYRK1AKO-COs would be used as optimum models for evaluating phenotypic ameliorations. Overdose drug exposure in DS-COs can be explained by similar defects present in DS-baDYRK1AKO-COs and DYRK1AKO-COs. There are several limitations in the current CO technology, which can be reduced by the generation of vascularized brain-like organoids giving opportunities to mimic late-stage corticogenesis and complete hippocampal development. In the future, improved DS-DYRK1AKO-COs can be efficient in studies that aim to generate efficiently transplantable and implantable neurons for tissue regeneration alternatives in DS individuals.

  4. Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood-brain barrier and metal homeostasis in cerebral cortex of rat brain: an in vivo and in vitro study.

    PubMed

    Mitra, Sumonto; Gera, Ruchi; Siddiqui, Waseem A; Khandelwal, Shashi

    2013-08-09

    Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30mg/kg) was administered and the animals were sacrificed on day 3 and day 7. Blood-brain barrier permeability remained disrupted significantly till day 7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 and NF-κB) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca(2+) inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT assay), signifying specific roles of Ca(2+) and ROS. Significance of p38 signaling was evaluated on pro-apoptotic proteins by using SB203580, a selective p38 inhibitor. Our data collectively illustrates that TBTC can disrupt BBB, induce oxidative stress, cause cell death and initiate neurodegeneration in rat brain.

  5. Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis.

    PubMed

    Frøkjaer, Vibe G; Strauss, Gitte I; Mehlsen, Jesper; Knudsen, Gitte M; Rasmussen, Verner; Larsen, Fin S

    2006-06-01

    Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child-Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).NE increased blood pressure similarly in the controls (27 (24-32) mmHg) and patients with the most severe liver cirrhosis (Child-Pugh C, 31 (26-44) mmHg, p=0.405 Mann-Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child-Pugh C, 26 (24-39) %; controls, 3 (-1.3 to 3) %; respectively, p=0.016, Mann-Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child-Pugh C, 6.0+/-2.0 bpm) compared to the controls (21.7+/-2.2 bpm, p=0.001, Tukey' test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis. Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.

  6. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

  7. Complications of endovascular treatment of cerebral aneurysms.

    PubMed

    Orrù, Emanuele; Roccatagliata, Luca; Cester, Giacomo; Causin, Francesco; Castellan, Lucio

    2013-10-01

    The number of neuroendovascular treatments of both ruptured and unruptured aneurysms has increased substantially in the last two decades. Complications of endovascular treatments of cerebral aneurysms are rare but can potentially lead to acute worsening of the neurological status, to new neurological deficits or death. Some of the possible complications, such as vascular access site complications or systemic side effects associated with contrast medium (e.g. contrast medium allergy, contrast induced nephropathy) can also be encountered in diagnostic angiography. The most common complications of endovascular treatment of cerebral aneurysms are related to acute thromboembolic events and perforation of the aneurysm. Overall, the reported rate of thromboembolic complications ranges between 4.7% and 12.5% while the rate of intraprocedural rupture of cerebral aneurysms is about 0.7% in patients with unruptured aneurysms and about 4.1% in patients with previously ruptured aneurysms. Thromboembolic and hemorrhagic complications may occur during different phases of endovascular procedures and are related to different technical, clinical and anatomic reasons. A thorough knowledge of the different aspects of these complications can reduce the risk of their occurrence and minimize their clinical sequelae. A deep understanding of complications and of their management is thus part of the best standard of care.

  8. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    PubMed

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy.

  9. Opiates and cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  10. Focal embolic cerebral ischemia in the rat

    PubMed Central

    Zhang, Li; Zhang, Rui Lan; Jiang, Quan; Ding, Guangliang; Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 hours of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we have developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. The surgical procedures of our model can be typically completed within approximately 30 min and are highly adaptable to other strains of rats as well as mice for both genders. Thus, this model provides a powerful tool for translational stroke research. PMID:25741989

  11. The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.

    PubMed

    Cao, Yanjing; Liang, Lizhen; Xu, Jian; Wu, Jiali; Yan, Yongxing; Lin, Ping; Chen, Qiang; Zheng, Fengming; Wang, Qin; Ren, Qian; Gou, Zengmei; Du, Yifeng

    2016-05-01

    Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3β and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD.

  12. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  13. Resting cerebral blood flow

    PubMed Central

    Ances, B M.; Sisti, D; Vaida, F; Liang, C L.; Leontiev, O; Perthen, J E.; Buxton, R B.; Benson, D; Smith, D M.; Little, S J.; Richman, D D.; Moore, D J.; Ellis, R J.

    2009-01-01

    Objective: HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC). Methods: This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV− subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated. Results: rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV− subjects. A 2-tiered CART approach using either LN rCBF ≤50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF ≤37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV− controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects. Conclusion: Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment. GLOSSARY AEH = acute/early HIV infection; ANOVA = analysis of variance; ASL-MRI = arterial spin labeling MRI; CART = classification and regression tree; CBF = cerebral blood flow; CH = chronic HIV

  14. Cerebral Disorders of Calves.

    PubMed

    Dore, Vincent; Smith, Geof

    2017-03-01

    Neurologic diseases of the cerebrum are relatively common in cattle. In calves, the primary cerebral disorders are polioencephalomalacia, meningitis, and sodium toxicity. Because diagnostic testing is not always readily available, the practitioner must often decide on a course of treatment based on knowledge of the likely disease, as well as his or her own clinical experience. This is particularly true with neurologic diseases in which the prognosis is often poor and euthanasia may be the most humane outcome. This article reviews the most common diseases affecting the cerebrum of calves with a focus on pathophysiology, diagnosis, and treatment.

  15. Nicotinamide restores the reduction of parvalbumin in cerebral ischemic injury.

    PubMed

    Koh, Phil-Ok

    2013-02-01

    The aim of this study investigated whether nicotinamide affects parvalbumin expression in focal cerebral ischemic injury. Rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after middle cerebral artery occlusion (MCAO), and cerebral cortex tissues were collected 24 hr after MCAO. Nicotinamide significantly decreases the volume of infarct areas in the cerebral cortex. A proteomic approach revealed that MCAO induces decreases of parvalbumin levels, while nicotinamide treatment prevents injury-induced decreases in parvalbumin. RT-PCR and Western blot analyses demonstrated that nicotinamide restores injury-induced decreases in parvalbumin. Moreover, immunohistochemical staining confirmed that the numbers of parvalbumin-positive cells were decreased in vehicle-treated animals with MCAO, and that nicotinamide averted this decrease. In cultured hippocampal cells, nicotinamide treatment prevents the glutamate exposure-induced increase in intracellular Ca(2+) concentration and decrease in parvalbumin expression. These results suggest the fact that the maintenance of parvalbumin expression is mediated to the neuroprotective function of nicotinamide against ischemic brain injury.

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

    PubMed

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

    2013-11-01

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

  17. The effects of oxiracetam (CT-848) on local cerebral glucose utilization after focal cerebral ischemia in rats.

    PubMed

    Hokonohara, T; Sako, K; Shinoda, Y; Tomabechi, M; Yonemasu, Y

    1992-02-01

    The effects of oxiracetam on the reduction of brain metabolism induced by focal cerebral ischemia were investigated by measuring local cerebral glucose utilization (LCGU) in rats 24 hr after left middle cerebral artery occlusion. Focal cerebral ischemia reduced LCGU in the entire ipsilateral cortex, the greatest reduction being in the lateral parts of the frontoparietal cortex. LCGU was slightly reduced in the contralateral cortex; this reduction was considered to be caused by diaschisis. Oxiracetam was administered intraperitoneally for 3 days prior to middle cerebral artery occlusion. In the ipsilateral cortex, LCGU reduction was minimized in the ischemic center areas by oxiracetam at a dose of 400 mg/kg and in more extensive areas, by a dose of 800 mg/kg. Moreover, oxiracetam at a dose of 800 mg/kg enhanced metabolism impaired by diaschisis in the caudal areas of the contralateral cortex. These findings suggest that oxiracetam minimizes the reduction of brain function induced by ischemia and may therefore be useful in the treatment of cerebrovascular disease.

  18. Cerebral Gluconeogenesis and Diseases

    PubMed Central

    Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

    2017-01-01

    The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions. PMID:28101056

  19. Cerebral cartography and connectomics

    PubMed Central

    Sporns, Olaf

    2015-01-01

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870

  20. Cerebral hyperperfusion syndrome.

    PubMed

    van Mook, Walther N K A; Rennenberg, Roger J M W; Schurink, Geert Willem; van Oostenbrugge, Robert Jan; Mess, Werner H; Hofman, Paul A M; de Leeuw, Peter W

    2005-12-01

    Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is characterised by ipsilateral headache, hypertension, seizures, and focal neurological deficits. If not treated properly it can result in severe brain oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS among physicians is limited. Most studies report incidences of CHS of 0-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in perfusion compared with baseline after carotid endarterectomy and is rare in patients with increases in perfusion less than 100% compared with baseline. The most important risk factors in CHS are diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours after carotid endarterectomy. Impaired autoregulation as a result of endothelial dysfunction mediated by generation of free oxygen radicals is implicated in the pathogenesis of CHS. Treatment strategies are directed towards regulation of blood pressure and limitation of rises in cerebral perfusion. Complete recovery happens in mild cases, but disability and death can occur in more severe cases. More information about CHS and early institution of adequate treatment are of paramount importance in order to prevent these potentially severe complications.

  1. Cerebral cartography and connectomics.

    PubMed

    Sporns, Olaf

    2015-05-19

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics.

  2. Monitoring of cerebral autoregulation.

    PubMed

    Czosnyka, Marek; Miller, Chad

    2014-12-01

    Pressure autoregulation is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure (CPP). Static autoregulation represents how far cerebrovascular resistance changes when CPP varies, and dynamic autoregulation represents how fast these changes happen. Both have been monitored in the setting of neurocritical care to aid prognostication and contribute to individualizing CPP targets in patients. Failure of autoregulation is associated with a worse outcome in various acute neurological diseases. Several studies have used transcranial Doppler ultrasound, intracranial pressure (ICP with vascular reactivity as surrogate measure of autoregulation), and near-infrared spectroscopy to continuously monitor the impact of spontaneous fluctuations in CPP on cerebrovascular physiology and to calculate derived variables of autoregulatory efficiency. Many patients who undergo such monitoring demonstrate a range of CPP in which autoregulatory efficiency is optimal. Management of patients at or near this optimal level of CPP is associated with better outcomes in traumatic brain injury. Many of these studies have utilized the concept of the pressure reactivity index, a correlation coefficient between ICP and mean arterial pressure. While further studies are needed, these data suggest that monitoring of autoregulation could aid prognostication and may help identify optimal CPP levels in individual patients.

  3. Cerebral sinus venous thrombosis

    PubMed Central

    Alvis-Miranda, Hernando Raphael; Milena Castellar-Leones, Sandra; Alcala-Cerra, Gabriel; Rafael Moscote-Salazar, Luis

    2013-01-01

    Cerebral sinus venous thrombosis (CSVT) is a rare phenomenon that can be seen with some frequency in young patients. CSVT is a multifactorial condition with gender-related specific causes, with a wide clinical presentation, the leading causes differ between developed and developing countries, converting CSVT in a condition characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis that requires fine medical skills and a high suspicious index. Patients who presents with CSVT should underwent to CT-scan venography (CVT) and to the proper inquiry of the generating cause. This disease can affect the cerebral venous drainage and related anatomical structure. The symptoms may appear in relation to increased intracranial pressure imitating a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the cause, generally the complications can be prevented. Mortality trends have diminished, and with the new technologies, surely it will continue. This work aims to review current knowledge about CSVT including its pathogenesis, etiology, clinical manifestations, diagnosis, and treatment. PMID:24347950

  4. [Noradrenaline and cerebral aging].

    PubMed

    Jouvet, M; Albarede, J L; Lubin, S; Meyrignac, C

    1991-01-01

    The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson's disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders.

  5. Dynamic cerebral autoregulation measured with coherent hemodynamics spectroscopy (CHS)

    NASA Astrophysics Data System (ADS)

    Kainerstorfer, Jana M.; Sassaroli, Angelo; Tgavalekos, Kristen T.; Fantini, Sergio

    2015-03-01

    Coherent Hemodynamics Spectroscopy (CHS) is a novel technique for non-invasive measurements of local microcirculation quantities such as the capillary blood transit times and dynamic autoregulation. The basis of CHS is to measure, for instance with near-infrared spectroscopy (NIRS), peripheral coherent hemodynamic changes that are induced by controlled perturbations in the systemic mean arterial pressure (MAP). In this study, the MAP perturbation was induced by the fast release of two pneumatic cuffs placed around the subject's thighs after they were kept inflated (at 200 mmHg) for two minutes. The resulting transient changes in cerebral oxy- (O) and deoxy- (D) hemoglobin concentrations measured with NIRS on the prefrontal cortex are then described by a novel hemodynamic model, from which quantifiable parameters such as the capillary blood transit time and a cutoff frequency for cerebral autoregulation are obtained. We present results on eleven healthy volunteers in a protocol involving measurements during normal breathing and during hyperventilation, which is known to cause a hypocapnia-induced increase in cerebral autoregulation. The measured capillary transit time was unaffected by hyperventilation (normal breathing: 1.1±0.1 s; hyperventilation: 1.1±0.1 s), whereas the cutoff frequency of autoregulation, which increases for higher autoregulation efficiency, was indeed found to be significantly greater during hyperventilation (normal breathing: 0.017±0.002 Hz; hyperventilation: 0.034±0.005 Hz). These results provide a validation of local cerebral autoregulation measurements with the new technique of CHS.

  6. Cerebral organoids model human brain development and microcephaly.

    PubMed

    Lancaster, Madeline A; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S; Hurles, Matthew E; Homfray, Tessa; Penninger, Josef M; Jackson, Andrew P; Knoblich, Juergen A

    2013-09-19

    The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

  7. Induction of Expansion and Folding in Human Cerebral Organoids.

    PubMed

    Li, Yun; Muffat, Julien; Omer, Attya; Bosch, Irene; Lancaster, Madeline A; Sur, Mriganka; Gehrke, Lee; Knoblich, Juergen A; Jaenisch, Rudolf

    2017-03-02

    An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids. This genetic modification allows sustained cell cycle re-entry, expansion of the progenitor population, and delayed neuronal differentiation, all key features of the developing human cortex. In contrast, Pten deletion in mouse organoids does not lead to folding. Finally, we utilized the expanded cerebral organoids to show that infection with Zika virus impairs cortical growth and folding. Our study provides new insights into the mechanisms regulating the structure and organization of the human cortex.

  8. Cerebral Arterial Fenestrations

    PubMed Central

    Cooke, Daniel L; Stout, Charles E; Kim, Warren T; Kansagra, Akash P; Yu, John Paul; Gu, Amy; Jewell, Nicholas P; Hetts, Steven W; Higashida, Randall T; Dowd, Christopher F; Halbach, Van V

    2014-01-01

    Summary Arterial fenestrations are an anatomic variant with indeterminate significance. Given the controversy surrounding fenestrations we sought their prevalence within our practice along with their association with other cerebrovascular anomalies. We retrospectively reviewed 10,927 patients undergoing digital subtraction angiography between 1992 and 2011. Dictated reports were searched for the terms “fenestration” or “fenestrated” with images reviewed for relevance, yielding 228 unique cases. A Medline database search from February 1964 to January 2013 generated 304 citations, 127 cases of which were selected for analysis. Cerebral arterial fenestrations were identified in 228 patients (2.1%). At least one aneurysm was noted in 60.5% of patients, with an aneurysm arising from the fenestration in 19.6% of patients. Aneurysmal subarachnoid hemorrhage or non-aneurysmal subarachnoid hemorrhage were present in 60.1% and 15.8%, respectively. For the subset of patients with an aneurysm arising directly from a fenestration relative to those patients with an aneurysm not immediately associated with a fenestration, the prevalence of aneurysmal subarachnoid hemorrhage was 66.7% vs. 58.6% (p = 0.58). Fenestrations were more often within the posterior circulation (73.2%) than the anterior circulation (24.6%), though there was no difference in the prevalence of aneurysms within these groups (61.1% vs. 60.7%, p = 1.0). Cerebral arterial fenestrations are an anatomic variant more often manifesting at the anterior communicating arterial complex and basilar artery and with no definite pathological relationship with aneurysms. PMID:24976087

  9. Cerebral autoregulation is compromised during simulated fluctuations in gravitational stress.

    PubMed

    Brown, Clive M; Dütsch, Matthias; Ohring, Susanne; Neundörfer, Bernhard; Hilz, Max J

    2004-03-01

    Gravity places considerable stress on the cardiovascular system but cerebral autoregulation usually protects the cerebral blood vessels from fluctuations in blood pressure. However, in conditions such as those encountered on board a high-performance aircraft, the gravitational stress is constantly changing and might compromise cerebral autoregulation. In this study we assessed the effect of oscillating orthostatic stress on cerebral autoregulation. Sixteen (eight male) healthy subjects [aged 27 (1) years] were exposed to steady-state lower body negative pressure (LBNP) at -15 and -40 mmHg and then to oscillating LBNP at the same pressures. The oscillatory LBNP was applied at 0.1 and 0.2 Hz. We made continuous recordings of RR-interval, blood pressure, cerebral blood flow velocity (CBFV), respiratory frequency and end-tidal CO(2). Oscillations in mean arterial pressure (MAP) and CBFV were assessed by autoregressive spectral analysis. Respiration was paced at 0.25 Hz to avoid interference from breathing. Steady-state LBNP at -40 mmHg significantly increased low-frequency (LF, 0.03-0.14 Hz) powers of MAP ( P<0.01) but not of CBFV. Oscillatory 0.1 Hz LBNP (0 to -40 mmHg) significantly increased the LF power of MAP to a similar level as steady-state LBNP but also resulted in a significant increase in the LF power of CBFV ( P<0.01). Oscillatory LBNP at 0.2 Hz induced oscillations in MAP and CBFV at 0.2 Hz. Cross-spectral analysis showed that the transfer of LBNP-induced oscillations in MAP onto the CBFV was significantly greater at 0.2 Hz than at 0.1 Hz ( P<0.01). These results show that the ability of the cerebral vessels to modulate fluctuations in blood pressure is compromised during oscillatory compared with constant gravitational stress. Furthermore, this effect seems to be more pronounced at higher frequencies of oscillatory stress.

  10. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    SciTech Connect

    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  11. Cerebral aneurysms following radiotherapy for medulloblastoma

    SciTech Connect

    Benson, P.J.; Sung, J.H.

    1989-04-01

    Three patients, two males and one female aged 21, 14, and 31 years, respectively, developed cerebral saccular aneurysms several years after undergoing radiotherapy for cerebellar medulloblastoma at 2, 5, and 14 years of age, respectively. Following surgery, all three received combined cobalt-60 irradiation and intrathecal colloidal radioactive gold (/sup 198/Au) therapy, and died from rupture of the aneurysm 19, 9, and 17 years after the radiotherapy, respectively. Autopsy examination revealed no recurrence of the medulloblastoma, but widespread radiation-induced vasculopathy was found at the base of the brain and in the spinal cord, and saccular aneurysms arose from the posterior cerebral arteries at the basal cistern or choroidal fissure. The aneurysms differed from the ordinary saccular aneurysms of congenital type in their location and histological features. Their locations corresponded to the areas where intrathecally administered colloidal /sup 198/Au is likely to pool, and they originated directly from a segment of the artery rather than from a branching site as in congenital saccular aneurysms. It is, therefore, concluded that the aneurysms in these three patients were most likely radiation-induced.

  12. Cerebral hydatid disease in Britain

    PubMed Central

    Anderson, Milne; Bickerstaff, Edwin R.; Hamilton, J. G.

    1975-01-01

    Two cases of cerebral hydatid disease are described. This condition, acquired by Britons in Britain, is extremely rare as only two similar cases have been reported before. Details of clinical presentation, investigation and treatment are described. Images PMID:1206419

  13. Cerebral emboli of paradoxical origin.

    PubMed

    Jones, H R; Caplan, L R; Come, P C; Swinton, N W; Breslin, D J

    1983-03-01

    A diagnosis of paradoxical cerebral embolus (PCE) was made in five patients aged 31 to 62 years who sustained eight cerebral ischemic events. No patient had evidence of primary carotid system or left heart disease. A probe-patent foramen ovale was the presumed mechanism in four patients, and an unsuspected congenital atrial septal defect was found in the fifth patient. Clinically apparent pulmonary emboli or venous thrombosis preceded the cerebral event in only one instance. Review of the literature reveals a high mortality with PCE. However, careful clinical search for this lesion may be rewarding: four of our five patients survived. One should consider PCE in any patient with cerebral embolus in whom there is no demonstrable left-sided circulatory source. This principle applies particularly if there is concomitant venous thrombosis, pulmonary embolism, or enhanced potential for venous thrombosis due to, for example, morbid obesity, use of hormonal birth control pills, prolonged bed rest (especially postoperatively), or systemic carcinoma.

  14. Cerebral ganglioglioma. A Golgi study.

    PubMed

    Ferrer, I; Ribalta, T; Digon, E; Acebes, J

    1983-01-01

    The morphological characteristics of neurons revealed by Golgi's method are reported in a case of cerebral ganglioglioma. Spindle-shaped (leptodendritic) neurons and radiated type I neurons form the bulk of this tumour. According to Ramon-Moliner (1968) isodendritic neurons (both leptodendritic and radiate type I) are philogenetically primitive cells and differ greatly from those observed in most of the deep cerebral nuclei of the mammalian's brain.

  15. Resource Allocation in Cerebral Specialization.

    DTIC Science & Technology

    1980-01-01

    of this multiple-resources view. EXTENSION OF THE THEORY TO THE TWO CEREBRAL HEMISPHERES Since the anatomical division of the brain invites...performance differences between the hemispheres (e.g., right-handed males with no familial history of left- handedness who use a normal rather than an...G. Beaumont (Eds.), Hemisphere function in the human rain.. New York: Halstead Press, 1974. Kinsbourne, M. The cerebral basis of lateral asymmetries

  16. Adrenergic and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs

    SciTech Connect

    Armstead, W.M.; Leffler, C.W.; Busija, D.W.; Beasley, D.G.; Mirro, R. )

    1988-04-01

    The interaction between adrenergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious, hypotensive newborn pig was investigated. Pretreatment with the selective {alpha}{sub 1}- and {alpha}{sub 2}-adrenoceptor antagonists prazosin and yohimbine, respectively, had no effect on cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or after hemmorrhagic hypotension. Indomethacin treatment (5 mg/kg ia) of piglets following hemorrhage caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 54 and 177%, 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.42 {+-} 0.28 to 1.45 {+-} 0.28 ml{center dot}100 g{sup {minus}1} and to 1.0 {+-} 0.28 ml{center dot}100 g{sup {minus}1}{center dot}min{sup {minus}1} 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were the same as in animals pretreated with vehicle, prazosin, or yohimbine. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn, as reported previously. These data do not implicate removal of sympathetic modulation by prostanoids as a mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

  17. Therapeutic implications of melatonin in cerebral edema.

    PubMed

    Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit

    2014-12-01

    Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema.

  18. Increased Pulsatile Cerebral Blood Flow, Cerebral Vasodilation, and Post-syncopal Headache in Adolescents

    PubMed Central

    Ocon, Anthony J.; Messer, Zachary; Medow, Marvin S.; Stewart, Julian M.

    2011-01-01

    Objective We hypothesize that following a sudden decrease in cerebral blood flow velocity (CBFV) in adolescents at faint, rapid hyperemic pulsatile CBFV occurs upon the return to the supine position, and is associated with post-syncopal headache. Study design This case-control study involved 16 adolescent subjects with history of fainting and headaches. We induced faint during 70° tilt-table testing and measured mean arterial pressure (MAP), heart rate (HR), end-tidal CO2, and CBFV. Fifteen control subjects were similarly evaluated with a tilt but did not faint, and comparisons with fainters were made at equivalent defined time points. Results Baseline values were similar between groups. Upon fainting, MAP decreased 49% in fainters vs. 6% in controls (P<0.001). HR decreased 15% in fainters and increased 35% in controls (P<0.001). In fainters, cerebrovascular critical closing pressure increased markedly resulting in reduced diastolic (-66%) and mean CBFV (-46%) at faint; systolic CBFV was similar to controls. Pulsatile CBFV (systolic – diastolic CBFV) increased 38% in fainters, driving flow-mediated dilation of cerebral vessels. Returning to supine, fainters’ CBFV exhibited increased systolic and decreased diastolic flows compared with controls (P<0.02). Conclusion Increased pulsatile CBFV during and following faint may cause post-syncopal cerebral vasodilation and headache. PMID:21596391

  19. Anti-inflammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury

    PubMed Central

    Han, Jiang-quan; Liu, Cheng-ling; Wang, Zheng-yuan; Liu, Ling; Cheng, Ling; Fan, Ya-dan

    2016-01-01

    Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4 via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4. PMID:27212926

  20. Nitroxyl exacerbates ischemic cerebral injury and oxidative neurotoxicity.

    PubMed

    Choe, Chi-un; Lewerenz, Jan; Fischer, Gerry; Uliasz, Tracy F; Espey, Michael Graham; Hummel, Friedhelm C; King, Stephen Bruce; Schwedhelm, Edzard; Böger, Rainer H; Gerloff, Christian; Hewett, Sandra J; Magnus, Tim; Donzelli, Sonia

    2009-09-01

    Nitroxyl (HNO) donor compounds function as potent vasorelaxants, improve myocardial contractility and reduce ischemia-reperfusion injury in the cardiovascular system. With respect to the nervous system, HNO donors have been shown to attenuate NMDA receptor activity and neuronal injury, suggesting that its production may be protective against cerebral ischemic damage. Hence, we studied the effect of the classical HNO-donor, Angeli's salt (AS), on a cerebral ischemia/reperfusion injury in a mouse model of experimental stroke and on related in vitro paradigms of neurotoxicity. I.p. injection of AS (40 mumol/kg) in mice prior to middle cerebral artery occlusion exacerbated cortical infarct size and worsened the persistent neurological deficit. AS not only decreased systolic blood pressure, but also induced systemic oxidative stress in vivo indicated by increased isoprostane levels in urine and serum. In vitro, neuronal damage induced by oxygen-glucose-deprivation of mature neuronal cultures was exacerbated by AS, although there was no direct effect on glutamate excitotoxicity. Finally, AS exacerbated oxidative glutamate toxicity - that is, cell death propagated via oxidative stress in immature neurons devoid of ionotropic glutamate receptors. Taken together, our data indicate that HNO might worsen cerebral ischemia-reperfusion injury by increasing oxidative stress and decreasing brain perfusion at concentrations shown to be cardioprotective in vivo.

  1. Correlation between cerebral oxygen metabolism and cerebral blood flow simultaneously measured before and after acetazolamide administration.

    PubMed

    Yamaguchi, H; Yamauchi, H; Hazama, S; Hamamoto, H; Inoue, N

    1999-10-01

    The cerebral circulation and metabolism of ten preoperative cardiac surgery patients were assessed. Alterations in regional cerebral blood flow (rCBF), measured by 123I-N-isopropyl-p-iodo-amphetamine single-photon emission computed tomography, and in cerebral oxygen metabolism, simultaneously detected by near-infrared spectroscopy (NIRS) before and after acetazolamide administration, were investigated. The rCBF (ml/min/100 g) increased significantly from 40.21±7.65 to 56.24±13.69(p<0.001), and a significant increase in oxyhemoglobin (Oxy-Hb) of 13.9% (p=0.0022) and total hemoglobin (Total-Hb) of 5.7% (0.0047) along with a significant decrease in deoxyhemoglobin (Deoxy-Hb) of 8.9% (p=0.0414) were observed concomitantly. Thus, the Oxy-Hb/Total-Hb ratio (%Oxy-Hb) rose significantly from 67.26±9.82% to 72.98±8.09%(p=0.0022). Examination of the relationships between individual parameters showed that the percentage changes in rCBF and Oxy-Hb were significantly correlated (r=0.758,p=0.011). The percentage changes in rCBF and %Oxy-Hb were also correlated significantly (r=0.740,p=0.014). In conclusion, this evidence suggested that NIRS is able to detect relative changes in cerebral hemodynamics and reflect luxury perfusion induced by acetazolamide. © 1999 Society of Photo-Optical Instrumentation Engineers.

  2. Monitoring Cerebral Oxygenation in Neonates: An Update

    PubMed Central

    Dix, Laura Marie Louise; van Bel, Frank; Lemmers, Petra Maria Anna

    2017-01-01

    Cerebral oxygenation is not always reflected by systemic arterial oxygenation. Therefore, regional cerebral oxygen saturation (rScO2) monitoring with near-infrared spectroscopy (NIRS) is of added value in neonatal intensive care. rScO2 represents oxygen supply to the brain, while cerebral fractional tissue oxygen extraction, which is the ratio between rScO2 and systemic arterial oxygen saturation, reflects cerebral oxygen utilization. The balance between oxygen supply and utilization provides insight in neonatal cerebral (patho-)physiology. This review highlights the potential and limitations of cerebral oxygenation monitoring with NIRS in the neonatal intensive care unit. P