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Sample records for rat brain coupled

  1. Connexin expression in electrically coupled postnatal rat brain neurons

    PubMed Central

    Venance, Laurent; Rozov, Andrei; Blatow, Maria; Burnashev, Nail; Feldmeyer, Dirk; Monyer, Hannah

    2000-01-01

    Electrical coupling by gap junctions is an important form of cell-to-cell communication in early brain development. Whereas glial cells remain electrically coupled at postnatal stages, adult vertebrate neurons were thought to communicate mainly via chemical synapses. There is now accumulating evidence that in certain neuronal cell populations the capacity for electrical signaling by gap junction channels is still present in the adult. Here we identified electrically coupled pairs of neurons between postnatal days 12 and 18 in rat visual cortex, somatosensory cortex, and hippocampus. Notably, coupling was found both between pairs of inhibitory neurons and between inhibitory and excitatory neurons. Molecular analysis by single-cell reverse transcription–PCR revealed a differential expression pattern of connexins in these identified neurons. PMID:10944183

  2. Automatic cropping of MRI rat brain volumes using pulse coupled neural networks.

    PubMed

    Murugavel, Murali; Sullivan, John M

    2009-04-15

    The Pulse Coupled Neural Network (PCNN) was developed by Eckhorn to model the observed synchronization of neural assemblies in the visual cortex of small mammals such as a cat. In this paper we show the use of the PCNN as an image segmentation strategy to crop MR images of rat brain volumes. We then show the use of the associated PCNN image 'signature' to automate the brain cropping process with a trained artificial neural network. We tested this novel algorithm on three T2 weighted acquisition configurations comprising a total of 42 rat brain volumes. The datasets included 40 ms, 48 ms and 53 ms effective TEs, acquisition field strengths of 4.7 T and 9.4 T, image resolutions from 64x64 to 256x256, slice locations ranging from +6 mm to -11 mm AP, two different surface coil manufacturers and imaging protocols. The results were compared against manually segmented gold standards and Brain Extraction Tool (BET) V2.1 results. The Jaccard similarity index was used for numerical evaluation of the proposed algorithm. Our novel PCNN cropping system averaged 0.93 compared to BET scores circa 0.84.

  3. Thiamine triphosphate synthesis in rat brain occurs in mitochondria and is coupled to the respiratory chain.

    PubMed

    Gangolf, Marjorie; Wins, Pierre; Thiry, Marc; El Moualij, Benaïssa; Bettendorff, Lucien

    2010-01-01

    In animals, thiamine deficiency leads to specific brain lesions, generally attributed to decreased levels of thiamine diphosphate, an essential cofactor in brain energy metabolism. However, another far less abundant derivative, thiamine triphosphate (ThTP), may also have a neuronal function. Here, we show that in the rat brain, ThTP is essentially present and synthesized in mitochondria. In mitochondrial preparations from brain (but not liver), ThTP can be produced from thiamine diphosphate and P(i). This endergonic process is coupled to the oxidation of succinate or NADH through the respiratory chain but cannot be energized by ATP hydrolysis. ThTP synthesis is strongly inhibited by respiratory chain inhibitors, such as myxothiazol and inhibitors of the H(+) channel of F(0)F(1)-ATPase. It is also impaired by disruption of the mitochondria or by depolarization of the inner membrane (by protonophores or valinomycin), indicating that a proton-motive force (Deltap) is required. Collapsing Deltap after ThTP synthesis causes its rapid disappearance, suggesting that both synthesis and hydrolysis are catalyzed by a reversible H(+)-translocating ThTP synthase. The synthesized ThTP can be released from mitochondria in the presence of external P(i). However, ThTP probably does not accumulate in the cytoplasm in vivo, because it is not detected in the cytosolic fraction obtained from a brain homogenate. Our results show for the first time that a high energy triphosphate compound other than ATP can be produced by a chemiosmotic type of mechanism. This might shed a new light on our understanding of the mechanisms of thiamine deficiency-induced brain lesions.

  4. Biofuel cell based on microscale nanostructured electrodes with inductive coupling to rat brain neurons.

    PubMed

    Andoralov, Viktor; Falk, Magnus; Suyatin, Dmitry B; Granmo, Marcus; Sotres, Javier; Ludwig, Roland; Popov, Vladimir O; Schouenborg, Jens; Blum, Zoltan; Shleev, Sergey

    2013-11-20

    Miniature, self-contained biodevices powered by biofuel cells may enable a new generation of implantable, wireless, minimally invasive neural interfaces for neurophysiological in vivo studies and for clinical applications. Here we report on the fabrication of a direct electron transfer based glucose/oxygen enzymatic fuel cell (EFC) from genuinely three-dimensional (3D) nanostructured microscale gold electrodes, modified with suitable biocatalysts. We show that the process underlying the simple fabrication method of 3D nanostructured electrodes is based on an electrochemically driven transformation of physically deposited gold nanoparticles. We experimentally demonstrate that mediator-, cofactor-, and membrane-less EFCs do operate in cerebrospinal fluid and in the brain of a rat, producing amounts of electrical power sufficient to drive a self-contained biodevice, viz. 7 μW cm(-2) in vitro and 2 μW cm(-2) in vivo at an operating voltage of 0.4 V. Last but not least, we also demonstrate an inductive coupling between 3D nanobioelectrodes and living neurons.

  5. Biofuel Cell Based on Microscale Nanostructured Electrodes with Inductive Coupling to Rat Brain Neurons

    PubMed Central

    Andoralov, Viktor; Falk, Magnus; Suyatin, Dmitry B.; Granmo, Marcus; Sotres, Javier; Ludwig, Roland; Popov, Vladimir O.; Schouenborg, Jens; Blum, Zoltan; Shleev, Sergey

    2013-01-01

    Miniature, self-contained biodevices powered by biofuel cells may enable a new generation of implantable, wireless, minimally invasive neural interfaces for neurophysiological in vivo studies and for clinical applications. Here we report on the fabrication of a direct electron transfer based glucose/oxygen enzymatic fuel cell (EFC) from genuinely three-dimensional (3D) nanostructured microscale gold electrodes, modified with suitable biocatalysts. We show that the process underlying the simple fabrication method of 3D nanostructured electrodes is based on an electrochemically driven transformation of physically deposited gold nanoparticles. We experimentally demonstrate that mediator-, cofactor-, and membrane-less EFCs do operate in cerebrospinal fluid and in the brain of a rat, producing amounts of electrical power sufficient to drive a self-contained biodevice, viz. 7 μW cm−2 in vitro and 2 μW cm−2 in vivo at an operating voltage of 0.4 V. Last but not least, we also demonstrate an inductive coupling between 3D nanobioelectrodes and living neurons. PMID:24253492

  6. Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain

    SciTech Connect

    Sumners, C.; Wei Tang; Zelezna, B.; Raizada, M.K. )

    1991-09-01

    Both neurons and astrocytes contain specific receptors for angiotensin II (AII). The authors used selective ligands for the AT{sub 1} and AT{sub 2} types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of {sup 125}I-labeled AII ({sup 125}I-AII) specific binding with AT{sub 1} (DuP753) or AT{sub 2} {l brace}PD123177, CGP42112A, (Phe(p-NH{sub 2}){sup 6})AII{r brace} selective receptor ligands revealed a potency series of AII > DuP753 > > > CGP42112A > (Phe(p-NH{sub 2}){sup 6})AII > PD123177. These results suggest a predominance of the AT{sub 1} receptor subtype in neonatal astrocytes. {sup 125}I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 {mu} MPD123177, and the residual {sup 125}I-AII specific binding was eliminated by DuP753. The results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT{sub 1} receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT{sub 2} receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT{sub 1} receptors is also present in these neurons.

  7. Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA,‘ecstasy’) exposure

    PubMed Central

    Coman, Daniel; Sanganahalli, Basavaraju G.; Jiang, Lihong; Hyder, Fahmeed; Behar, Kevin L.

    2015-01-01

    (+/−)3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is an abused psychostimulant producing strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCP), primarily a type specific to skeletal muscle (UCP-3) and which is absent in brain, although other UCP types are expressed in brain (e.g., thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights of MDMA action, we measured spatial distributions of systemically-administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation of Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA4−)). The MDMA-induced temperature rise in cortex was greater than in subcortex (1.6±0.4°C vs. 1.3±0.4°C) and occurred more rapidly (2.0±0.2°C/h vs. 1.5±0.2°C/h). MDMA-induced temperature changes and dynamics in cortex and body were correlated, although body temperature exceeded cortex before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in cortex and subcortex (i.e., thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to cortex, a biphasic relationship was seen in subcortex (i.e., thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature >37°C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as

  8. Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") exposure.

    PubMed

    Coman, Daniel; Sanganahalli, Basavaraju G; Jiang, Lihong; Hyder, Fahmeed; Behar, Kevin L

    2015-10-01

    (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an abused psychostimulant that produces strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP-3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA(4-))). The MDMA-induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA-induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions

  9. Purification and identification of the functional sodium- and chloride-coupled gamma-aminobutyric acid transport glycoprotein from rat brain.

    PubMed

    Radian, R; Bendahan, A; Kanner, B I

    1986-11-25

    Using the reconstitution conditions developed recently (Radian, R., and Kanner, B. I. (1985) J. Biol. Chem. 260, 11859-11865) we have now purified the sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain to apparent homogeneity. A partially purified transporter preparation was passed over wheat germ agglutinin-Sepharose 6MB and non-bound proteins were washed away. The transport activity, as expressed upon reconstitution of the protein into liposomes, was eluted by a solution containing Triton X-100 and N-acetylglucosamine. The specific transport activity was increased almost 400-fold over that of the crude extract. Taking into account an approximately 2.5-fold inactivation during the lectin column chromatography, the actual purification is about 1000-fold. Sodium dodecyl sulfate-polyacrylamide electrophoresis of the active fractions revealed one band of 80 kDa and small amounts of a band which ran at an apparent molecular mass of 160 kDa. The ratio between the two could be experimentally changed such as, for instance, by lyophilization. Polyclonal antibodies were prepared against the 80-kDa band which also cross-reacted with the 160-kDa band, indicating that the latter apparently represents a dimer form of the first. Using Protein A-Sepharose Cl-4B and the antibody against the 80-kDa band, we were able to quantitatively immunoprecipitate the potential gamma-aminobutyric acid transport activity from a crude transporter preparation. The pure transporter preparation exhibited the same features of the transporter in synaptic plasma membrane vesicles, namely dependence on sodium and chloride, electrogeneity, affinity, and efflux and exchange properties. We conclude that the 80-kDa band represents the gamma-aminobutyric acid transporter.

  10. Implanted, inductively-coupled, radiofrequency coils fabricated on flexible polymeric material: Application to in vivo rat brain MRI at 7 T

    NASA Astrophysics Data System (ADS)

    Ginefri, J.-C.; Rubin, A.; Tatoulian, M.; Woytasik, M.; Boumezbeur, F.; Djemaï, B.; Poirier-Quinot, M.; Lethimonnier, F.; Darrasse, L.; Dufour-Gergam, E.

    2012-11-01

    Combined with high-field MRI scanners, small implanted coils allow for high resolution imaging with locally improved SNR, as compared to external coils. Small flexible implantable coils dedicated to in vivo MRI of the rat brain at 7 T were developed. Based on the Multi-turn Transmission Line Resonator design, they were fabricated with a Teflon substrate using copper micromolding process and a specific metal-polymer adhesion treatment. The implanted coils were made biocompatible by PolyDimethylSiloxane (PDMS) encapsulation. The use of low loss tangent material achieves low dielectric losses within the substrate and the use of the PDMS layer reduces the parasitic coupling with the surrounding media. An implanted coil was implemented in a 7 T MRI system using inductive coupling and a dedicated external pick-up coil for signal transmission. In vivo images of the rat brain acquired with in plane resolution of (150 μm)2 thanks to the implanted coil revealed high SNR near the coil, allowing for the visualization of fine cerebral structures.

  11. Simultaneous determination of nicotine and its metabolite, cotinine, in rat blood and brain tissue using microdialysis coupled with liquid chromatography: pharmacokinetic application.

    PubMed

    Chang, Yuh-Lih; Tsai, Pi-Lo; Chou, Yueh-Ching; Tien, Jung-Hsiung; Tsai, Tung-Hu

    2005-09-23

    To elucidate the disposition of nicotine in the brain is important because the neuropharmacological effects from nicotine exposure are centrally predominated. The aim of the present study was to develop a rapid and simple method for the simultaneous determination of unbound nicotine and its main metabolite, cotinine, in rat blood and brain tissue. We coupled a multiple sites microdialysis sampling technique with HPLC-UV system to characterize the pharmacokinetics of both nicotine and cotinine. Microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats, and nicotine (2 mg/kg, i.v.) was administered via the femoral vein. Dialysates were collected every 10 min and injected directly into a HPLC system. Both nicotine and cotinine were separated by a phenyl-hexyl column (150 mm x 4.6 mm) from dialysates within 12 min. The mobile phase consisted of an acetonitrile-methanol-20 mM monosodium phosphate buffer (55:45:900, v/v/v, pH adjusted to 5.1) with a flow-rate of 1 ml/min. The wavelength of the UV detector was set at 260 nm. The limit of quantification for nicotine and cotinine were 0.25 microg/ml and 0.05 microg/ml, respectively. Intra- and inter-day precision and accuracy of both measurements fell well within the predefined limits of acceptability. The blood and brain concentration-time profile of nicotine and cotinine suggests that nicotine is easily to get into the central nervous system and cotinine exhibits a long retention time and accumulates in blood.

  12. Reduction in LFP cross-frequency coupling between theta and gamma rhythms associated with impaired STP and LTP in a rat model of brain ischemia.

    PubMed

    Xu, Xiaxia; Zheng, Chenguang; Zhang, Tao

    2013-01-01

    The theta-gamma cross-frequency coupling (CFC) in hippocampus was reported to reflect memory process. In this study, we measured the CFC of hippocampal local field potentials (LFPs) in a two-vessel occlusion (2VO) rat model, combined with both amplitude and phase properties and associated with short and long-term plasticity indicating the memory function. Male Wistar rats were used and a 2VO model was established. STP and LTP were recorded in hippocampal CA3-CA1 pathway after LFPs were collected in both CA3 and CA1. Based on the data of relative power spectra and phase synchronization, it suggested that both the amplitude and phase coupling of either theta or gamma rhythm were involved in modulating the neural network in 2VO rats. In order to determine whether the CFC was also implicated in neural impairment in 2VO rats, the coupling of CA3 theta-CA1 gamma was measured by both phase-phase coupling (n:m phase synchronization) and phase-amplitude coupling. The attenuated CFC strength in 2VO rats implied the impaired neural communication in the coordination of theta-gamma entraining process. Moreover, compared with modulation index (MI) a novel algorithm named cross frequency conditional mutual information (CF-CMI), was developed to focus on the coupling between theta phase and the phase of gamma amplitude. The results suggest that the reduced CFC strength probably attributed to the disruption of the phase of CA1 gamma envelop. In conclusion, it implied that the phase coupling and CFC of hippocampal theta and gamma played an important role in supporting functions of neural network. Furthermore, synaptic plasticity on CA3-CA1 pathway was reduced in line with the decreased CFC strength from CA3 to CA1. It partly supported our hypothesis that directional CFC indicator might probably be used as a measure of synaptic plasticity.

  13. Coupled heterocellular arrays in the brain.

    PubMed

    Fróes, M M; Menezes, J R L

    2002-11-01

    Gap junctions are transcellular pathways that enable a dynamic metabolic coupling and a selective exchange of biological signaling mediators. Throughout the course of the brain development these intercellular channels are assembled into regionally and temporally defined patterns. The present review summarizes the possibilities of heterocellular gap junctional pairing in the brain parenchyma, involving glial cells, neurons and neural precursors as well as it highlights on the meaningfulness of these coupled arrays to the concept of brain functional compartments.

  14. Imaging of uranium on rat brain sections using laser ablation inductively coupled plasma mass spectrometry: a new tool for the study of critical substructures affined to heavy metals in tissues.

    PubMed

    Becker, J Sabine; Dobrowolska, Justina; Zoriy, Miroslav; Matusch, Andreas

    2008-09-01

    The specific toxicity of trace metals and compounds largely depends on their bioavailability in different organs or compartments of the organism considered. Imaging mass spectrometry (IMS) using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) with a spatial resolution in the 100 microm range was developed and employed to study heavy metal distribution in brain tissues for toxicological screening. Rat brain post-mortem tissues were stained in an aqueous solution of either uranium or neodymium (metal concentration 100 microg g(-1)) for 3 h. The incubation of heavy metal in thin slices of brain tissue is followed by an imaging mass spectrometric LA-ICP-MS technique. Stained rat brain tissue (thickness 30 microm) were scanned with a focused laser beam (wavelength 266 nm, diameter of laser crater 100 microm and laser power density 3 x 10(9) W cm(-2)). The ion intensities of (235)U(+), (238)U(+), (145)Nd(+) and (146)Nd(+) were measured by LA-ICP-MS within the ablated area. For quantification purposes, matrix-matched laboratory standards were prepared by dosing each analyte to the pieces of homogenized brain tissue. Imaging LA-ICP-MS allows structures of interest to be identified and the relevant dose range to be estimated.

  15. Divergent Developmental Expression and Function of the Proton-Coupled Oligopeptide Transporters PepT2 and PhT1 in Regional Brain Slices of Mouse and Rat

    PubMed Central

    Hu, Yongjun; Xie, Yehua; Keep, Richard F.; Smith, David E.

    2014-01-01

    This study evaluated the developmental gene and protein expression of proton-coupled oligopeptide transporters (POTs: PepT1, PepT2, PhT1 and PhT2) in different regions of rodent brain, and the age-dependent uptake of a POT substrate, glycylsarcosine, in brain slices. Slices were obtained from cerebral cortex, cerebellum and hypothalamus of wildtype and PepT2 null mice, and from rats at different ages. Gene and protein expression were determined by real-time PCR and immunoblot analyses. Brain slice uptakes of radiolabeled glycylsarcosine were determined in the absence and presence of excess unlabeled glycylsarcosine or L-histidine, the latter being an inhibitor of PhT1/2 but not PepT1/2. Whereas PepT2 and PhT1 transcripts were abundantly expressed in all three regions of mouse brain, little to no expression was observed for PepT1 and PhT2. PhT1 protein was present in brain regions of adult but not neonatal mice and expression levels increased with age in rats. Glycylsarcosine uptake, inhibition and transporter dominance did not show regional brain or species differences. However, there were clear age-related differences in functional activity, with PepT2 dominating in neonatal mice and rats, and PhT1 dominating in adult rodents. These developmental changes may markedly impact the neural activity of both endogenous and exogenous (drug) peptides/mimetics. PMID:24548120

  16. The rat brain hippocampus proteome.

    PubMed

    Fountoulakis, Michael; Tsangaris, George T; Maris, Antony; Lubec, Gert

    2005-05-05

    The hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In humans, the CA1 area of hippocampus is one of the first brain areas to display pathology in Alzheimer's disease. A comprehensive analysis of the hippocampus proteome has not been accomplished yet. We applied proteomics technologies to construct a two-dimensional database for rat brain hippocampus proteins. Hippocampus samples from eight months old animals were analyzed by two-dimensional electrophoresis and the proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The database comprises 148 different gene products, which are in the majority enzymes, structural proteins and heat shock proteins. It also includes 39 neuron specific gene products. The database may be useful in animal model studies of neurological disorders.

  17. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    PubMed

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH.

  18. Comparative imaging of P, S, Fe, Cu, Zn and C in thin sections of rat brain tumor as well as control tissues by laser ablation inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zoriy, Myroslav V.; Dehnhardt, Markus; Matusch, Andreas; Becker, J. Sabine

    2008-03-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for quantitative imaging of selected elements (P, S, Fe, Cu, Zn and C) in thin sections of rat brain samples (thickness 20 μm). The sample surface was scanned (raster area ~ 2 cm 2) with a focused laser beam (wavelength 266 nm, diameter of laser crater 50 μm, and irradiance 1 × 10 9 W cm - 2 ). The laser ablation system was coupled to a double-focusing sector field. The possibility was evaluated of using carbon (via measurement of 13C +) as an internal standard element for imaging element distribution as part of this method. The LA-ICP-MS images obtained for P, S, Fe Cu and Zn were quantified using synthetically prepared matrix-matched laboratory standards. Depending on the sample analyzed, concentrations of Cu and Zn in the control tissue were found to be in the range of 8-10 μg g - 1 and 10-12 μg g - 1 , while in the tumor tissue these concentrations were in the range of 12-15 μg g - 1 and 15-17 μg g - 1 , respectively. The measurements of P, S and Fe distribution revealed the depletion of these elements in tumor tissue. In all the samples, the shape of the tumor could be clearly distinguished from the surrounding healthy tissue by the depletion in carbon. Additional experiments were performed in order to study the influence of the water content of the analyzed tissue on the intensity signal of the analyte. The results of these measurements show the linear correlation ( R2 = 0.9604) between the intensity of analyte and amount of water in the sample. The growth of a brain tumor was thus studied for the first time by imaging mass spectrometry.

  19. Deformation-based brain morphometry in rats.

    PubMed

    Gaser, Christian; Schmidt, Silvio; Metzler, Martin; Herrmann, Karl-Heinz; Krumbein, Ines; Reichenbach, Jürgen R; Witte, Otto W

    2012-10-15

    Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra-high field dedicated animal MRI systems. Here, we developed a novel deformation-based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of-interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats.

  20. Alcohol induced changes in phosphoinositide signaling system in rat brain

    SciTech Connect

    Pandey, S.; Piano, M.; Schwertz, D.; Davis, J.; Pandey, G. )

    1991-03-11

    Agonist-induced phosphoinositide break down functions as a signal generating system in a manner similar to the C-AMP system. In order to examine if the changes produced by chronic ethanol treatment on membrane lipid composition and metabolism effect the cellular functions of the neuron, the authors have examined the effect of chronic ethanol exposure on norepinephrine (NE) serotonin (5HT) and calcium ionophore (CI) stimulated phosphoinositide (PI) hydrolysis in rat cortical slices. Rats were maintained on liber-decarli diet alcohol and control liquid diet containing isocaloric sucrose substitute for two months. They were then sacrificed and brain was removed for determination of PI turnover. 5HT stimulated {sup 3}H- inositol monophosphate ({sup 3}H-IPI) formation was significantly lower in the cortex of alcohol treated rats as compared to control rats. However, neither CI nor NE stimulated IP1 formation was significantly different from control rats. The results thus indicate that chronic exposure to ethanol decreases 5HT induced PI breakdown in rat cortex. In order to examine if this decrease is related to a decrease in 5HT2 receptors, or decreased in coupling of receptor to the effector pathway, the authors are currently determining the number and affinity of 5HT2 receptors in alcohol treated rats.

  1. Laser scattering by transcranial rat brain illumination

    NASA Astrophysics Data System (ADS)

    Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

    2012-06-01

    Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

  2. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  3. EVALUATION OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT BRAIN

    EPA Science Inventory

    This study examined whether there is a differential distribution of PFOS within the brain, and compares adult rats with neonatal rats at an age when formation of the blood-brain barrier is not yet complete (postnatal day 7). Male and female Sprague-Dawley rats (60-70 day old, 4/...

  4. Effects of Acyzol on Zinc Content in Rat Brain and Blood Plasma.

    PubMed

    Yakimoskii, A F; Shantyr, I I; Vlasenko, M A; Yakovleva, M V

    2017-01-01

    Zinc level in the blood plasma and brain of rats was studied by inductively coupled plasma mass spectrometry. Maximum amount of zinc was observed in the cerebellum (15.0±5.5 μg/mg wet tissue). Single intraperitoneal administration of a zinc donor acyzol (24 mg/kg) did not change the content of this element in the tissues. Repeated injections of acyzol (7 injections over 14 days) significantly increased zinc level in rat plasma and brain. This elevation was most pronounced in the forebrain (cortex and subcortical structures). The rise in zinc concentration in blood plasma correlated with its level in the brain.

  5. Neurovascular coupling develops alongside neural circuits in the postnatal brain.

    PubMed

    Kozberg, Mariel G; Hillman, Elizabeth M C

    2016-01-01

    In the adult brain, increases in local neural activity are accompanied by increases in regional blood flow. This relationship between neural activity and hemodynamics is termed neurovascular coupling and provides the blood flow-dependent contrast detected in functional magnetic resonance imaging (fMRI). Neurovascular coupling is commonly assumed to be consistent and reliable from birth; however, numerous studies have demonstrated markedly different hemodynamics in the early postnatal brain. Our recent study in J. Neuroscience examined whether different hemodynamics in the immature brain are driven by differences in the underlying spatiotemporal properties of neural activity during this period of robust neural circuit expansion. Using a novel wide-field optical imaging technique to visualize both neural activity and hemodynamics in the mouse brain, we observed longer duration and increasingly complex patterns of neural responses to stimulus as cortical connectivity developed over time. However, imaging of brain blood flow, oxygenation, and metabolism in the same mice demonstrated an absence of coupled blood flow responses in the newborn brain. This lack of blood flow coupling was shown to lead to oxygen depletions following neural activations - depletions that may affect the duration of sustained neural responses and could be important to the vascular patterning of the rapidly developing brain. These results are a step toward understanding the unique neurovascular and neurometabolic environment of the newborn brain, and provide new insights for interpretation of fMRI BOLD studies of early brain development.

  6. Studies of aluminum in rat brain

    SciTech Connect

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  7. Coupled Harmonic Bases for Longitudinal Characterization of Brain Networks.

    PubMed

    Hwang, Seong Jae; Adluru, Nagesh; Collins, Maxwell D; Ravi, Sathya N; Bendlin, Barbara B; Johnson, Sterling C; Singh, Vikas

    2016-01-01

    There is a great deal of interest in using large scale brain imaging studies to understand how brain connectivity evolves over time for an individual and how it varies over different levels/quantiles of cognitive function. To do so, one typically performs so-called tractography procedures on diffusion MR brain images and derives measures of brain connectivity expressed as graphs. The nodes correspond to distinct brain regions and the edges encode the strength of the connection. The scientific interest is in characterizing the evolution of these graphs over time or from healthy individuals to diseased. We pose this important question in terms of the Laplacian of the connectivity graphs derived from various longitudinal or disease time points - quantifying its progression is then expressed in terms of coupling the harmonic bases of a full set of Laplacians. We derive a coupled system of generalized eigenvalue problems (and corresponding numerical optimization schemes) whose solution helps characterize the full life cycle of brain connectivity evolution in a given dataset. Finally, we show a set of results on a diffusion MR imaging dataset of middle aged people at risk for Alzheimer's disease (AD), who are cognitively healthy. In such asymptomatic adults, we find that a framework for characterizing brain connectivity evolution provides the ability to predict cognitive scores for individual subjects, and for estimating the progression of participant's brain connectivity into the future.

  8. Brain-to-Brain coupling: A mechanism for creating and sharing a social world

    PubMed Central

    Hasson, Uri; Ghazanfar, Asif A.; Galantucci, Bruno; Garrod, Simon; Keysers, Christian

    2012-01-01

    Cognition materializes in an interpersonal space. The emergence of complex behaviors requires the coordination of actions among individuals according to a shared set of rules. Despite the central role of other individuals in shaping our minds, most cognitive studies focus on processes that occur within a single individual. We call for a shift from a single-brain to a multi-brain frame of reference. We argue that in many cases the neural processes in one brain are coupled to the neural processes in another brain via the transmission of a signal through the environment. Brain-to-brain coupling constrains and simplifies the actions of each individual in a social network, leading to complex joint behaviors that could not have emerged in isolation. PMID:22221820

  9. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    SciTech Connect

    Periyasamy, S.; Hoss, W. )

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  10. Hybridizable ribonucleic acid of rat brain

    PubMed Central

    Bondy, S. C.; Roberts, Sidney

    1968-01-01

    1. Cerebral RNA of adult and newborn rats was labelled in vivo by intracervical injection of [5-3H]uridine or [32P]phosphate. Hepatic RNA of similar animals was labelled by intraperitoneal administration of [6-14C]orotic acid. Nuclear and cytoplasmic fractions were isolated and purified by procedures involving extraction with phenol and repeated precipitation with ethanol. 2. The fraction of pulse-labelled RNA from cerebral nuclei that hybridized to homologous DNA exhibited a wide range of turnover values and was heterogeneous in sucrose density gradients. 3. Base composition of the hybridizable RNA was similar to that of the total pulse-labelled material; both were DNA-like. 4. Pulse-labelled cerebral nuclear RNA hybridized to a greater extent than cytoplasmic RNA for at least a week after administration of labelled precursor. This finding suggested that cerebral nuclei contained a hybridizable component that was not transferred to cytoplasm. 5. The rates of decay of the hybridizable fractions of cerebral nuclei and cytoplasm were faster in the newborn animal than in the adult. Presumably a larger proportion of labile messenger RNA molecules was present in the immature brain. 6. Cerebral nuclear and cytoplasmic RNA fractions from newborn or adult rats, labelled either in vivo for periods varying from 4min. to 7 days or in vitro by exposure to [3H]-dimethyl sulphate, uniformly hybridized more effectively than the corresponding hepatic preparation. These data suggested that a larger proportion of RNA synthesis was oriented towards messenger RNA formation in brain than in liver. PMID:5683505

  11. Brain adaptation to acute hyponatremia in young rats.

    PubMed

    Silver, S M; Schroeder, B M; Bernstein, P; Sterns, R H

    1999-06-01

    Brain swelling after acute hyponatremia in prepubescent rats, in contrast to adults, has recently been associated with an increase in brain sodium and a high mortality that could be prevented by preadministration of testosterone. To reexamine the effect of acute hyponatremia in young brain, we measured brain water and solute content in prepubescent rats after induction of hyponatremia over 4 h with water and arginine vasopressin. An 18% decrease in plasma sodium was associated with a 13% increase in brain water and a decrease in brain sodium and glutamate contents. No animals died. To assess the effect of sex hormones on brain adaptation, prepubescent rats were pretreated with estrogen or testosterone before acute hyponatremia. Brain sodium and potassium contents were significantly reduced in comparison to normonatremia in testosterone-pretreated but not estrogen-pretreated animals. However, there was no difference between estrogen-pretreated and testosterone-pretreated groups in mortality or in brain contents of water, electrolytes, or major organic osmolytes. In conclusion, we found that brain adaptation to acute hyponatremia in prepubescent rats is similar to that observed in adults.

  12. Neurovascular coupling and energy metabolism in the developing brain

    PubMed Central

    Kozberg, M.; Hillman, E.

    2016-01-01

    In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

  13. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    NASA Astrophysics Data System (ADS)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja; Majumdar, Subrata; Jain, Sanjay K.

    2013-11-01

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  14. Aluminium toxicity in the rat liver and brain

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Ohashi, H.; Nagai, H.; Kakimi, S.; Ishikawa, A.; Kobayashi, K.; Ogawa, Y.; Ishii, K.

    1993-04-01

    To investigate the etiology of Alzheimer's disease, we examined the brain and liver tissue uptake of aluminium 5-75 days after aluminium injection into healthy rats. Ten days after the last injection, Al was detected in the brain and the brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Al was also demonstrated in the liver and the liver cell nuclei by PIXE analysis and electron energy loss spectrometry (EELS). The morphological changes of the rat brain examined 75 days after the injection were similar to those which have been reportedly observed in the brain of patients with Alzheimer's disease. These results support the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium in the brain, as well as in the nuclei of brain cells.

  15. 26Al uptake and accumulation in the rat brain

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Nagai, H.; Imamura, M.; Matsuzaki, H.; Hayashi, K.; Masuda, A.; Kumazawa, H.; Ohashi, H.; Kobayashi, K.

    1997-03-01

    To investigate the cause of Alzheimer's disease (senile dementia), 26Al incorporation in the rat brain was studied by accelerator mass spectrometry (AMS). When 26Al was injected into healthy rats, a considerable amount of 26Al entered the brain (cerebrum) through the blood-brain barrier 5 days after a single injection, and the brain 26Al level remained almost constant from 5 to 270 days. On the other hand, the level of 26Al in the blood decreased remarkably 75 days after injection. Approximately 89% of the 26Al taken in by the brain cell nuclei bound to chromatin. This study supports the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium (Al) in the brain, and brain cell nuclei.

  16. The Extended Mind: Coupling Environment and Brain

    NASA Astrophysics Data System (ADS)

    Vrobel, Susie

    2010-11-01

    This paper describes embodiment and cognitive extension as examples of strong anticipation as defined by Dubois. Clark and Chalmers formulated a thesis which states that parts of the environment, if coupled successfully, can become part of the extended mind. This coupling, be it deliberate or unintentional, shifts the observer-world boundary outwards when the observer encompasses parts of his environment. The resulting extended observer forms a new systemic whole, which consists of both the assimilated context and the recalibrated version of the original observer. Recalibration occurs when conditioning and adaptation lead to corresponding changes on the neural level, for instance, when an agent compensates for delays in a control loop. Plasticity is a prerequisite for any successful incorporation of external structures. However, uncoupled parts of the observer must remain inviolate in order to preserve the boundary. Neither the extended mind nor the core observer are absolute concepts. Depending on whether we focus on local-scale interactions or on large-scale behaviour, boundaries are formed at different interfacial cuts, which lead to either an endo- or an exo-perspective or endo- or exo-anticipation, respectively. For biological extended agents which undergo a transition from exo- to endo-states, a tell-tale sign of a successful exo-endo transition is invisibility. This invisibility occurs when the agent is no longer aware of the delay originally introduced into the control loop by the assimilated part of the environment. Explaining the world in terms of effective causality is not sufficient to account for extended minds. The latter require explanations in terms of final causation. For extended minds, this ordering principle comes in the shape of nested hierarchical layers. The interfaces of these layers may have merged for an endo-observer, whereas an exo-observer can make out the detailed structure, including artificially introduced delays. A sufficient

  17. Action of AF64A on rat brain muscarinic receptors

    SciTech Connect

    Eva, C.; Costa, E.

    1986-03-01

    ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.

  18. Transcranial Photoacoustic Measurements of Cold-Injured Brains in Rats

    NASA Astrophysics Data System (ADS)

    Ueda, Yoshinori; Sato, Shunichi; Hasegawa, Makoto; Nawashiro, Hiroshi; Saitoh, Daizoh; Shima, Katsuji; Ashida, Hiroshi; Obara, Minoru

    2005-09-01

    We performed transcranial photoacoustic measurements of cold-injured brains in rats. Before inducing injury, a signal peak was observed at two locations corresponding to the surfaces of the skull and brain, while after injury, a third peak appeared at a location corresponding to the back surface of the skull; the third peak was found to be caused by subdural hematoma. The signal peak for the brain surface shifted to a deeper region with elapse of time after injury, indicating deformation of the brain. These findings suggest that small hemorrhage and morphological change of the brain can be transcranially detected by photoacoustic measurement.

  19. Actin purification from a gel of rat brain extracts.

    PubMed

    Levilliers, N; Peron-Renner, M; Coffe, G; Pudles, J

    1984-01-01

    Actin, 99% pure, has been recovered from rat brain with a high yield (greater than 15 mg/100 g brain). We have shown that: 1. a low ionic strength extract from rat brain tissue is capable of giving rise to a gel; 2. actin is the main gel component and its proportion is one order of magnitude higher than in the original extract; 3. actin can be isolated from this extract by a three-step procedure involving gelation, dissociation of the gel in 0.6 M KCl, followed by one or two depolymerization-polymerization cycles.

  20. Effects of photoradiation therapy on normal rat brain

    SciTech Connect

    Cheng, M.K.; McKean, J.; Boisvert, D.; Tulip, J.; Mielke, B.W.

    1984-12-01

    Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. The authors conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

  1. Cross-frequency coupling in real and virtual brain networks

    PubMed Central

    Jirsa, Viktor; Müller, Viktor

    2013-01-01

    Information processing in the brain is thought to rely on the convergence and divergence of oscillatory behaviors of widely distributed brain areas. This information flow is captured in its simplest form via the concepts of synchronization and desynchronization and related metrics. More complex forms of information flow are transient synchronizations and multi-frequency behaviors with metrics related to cross-frequency coupling (CFC). It is supposed that CFC plays a crucial role in the organization of large-scale networks and functional integration across large distances. In this study, we describe different CFC measures and test their applicability in simulated and real electroencephalographic (EEG) data obtained during resting state. For these purposes, we derive generic oscillator equations from full brain network models. We systematically model and simulate the various scenarios of CFC under the influence of noise to obtain biologically realistic oscillator dynamics. We find that (i) specific CFC-measures detect correctly in most cases the nature of CFC under noise conditions, (ii) bispectrum (BIS) and bicoherence (BIC) correctly detect the CFCs in simulated data, (iii) empirical resting state EEG show a prominent delta-alpha CFC as identified by specific CFC measures and the more classic BIS and BIC. This coupling was mostly asymmetric (directed) and generally higher in the eyes closed (EC) than in the eyes open (EO) condition. In conjunction, these two sets of measures provide a powerful toolbox to reveal the nature of couplings from experimental data and as such allow inference on the brain state dependent information processing. Methodological advantages of using CFC measures and theoretical significance of delta and alpha interactions during resting and other brain states are discussed. PMID:23840188

  2. Brain-Spleen Inflammatory Coupling: A Literature Review

    PubMed Central

    Rasouli, J; Lekhraj, R; Ozbalik, M; Lalezari, P; Casper, D

    2012-01-01

    Recent evidence suggests a link between brain injury and the autonomic release of pro-inflammatory cytokines by resident macrophages in the spleen. This phenomenon, termed “brain-spleen inflammatory coupling,” has garnered attention from scientific and medical communities interested in developing novel treatments for traumatic brain injury (TBI). Cholinergic stimulation of the α7-subunit nicotinic acetylcholine receptor (α7NAchR) on splenic macrophages has been shown to inhibit their release of pro-inflammatory cytokines. This inhibition, mediated by the parasympathetic nervous system, has been shown to improve outcomes in animal models of sepsis, stroke, and TBI. As evidence of a beneficial role of splenic inhibition grows, new treatment strategies might be applied to many medical conditions involving neuroinflammation, a process that contributes to further neurological deterioration. PMID:22611344

  3. Induction of oxidative stress in rat brain by acrylonitrile (ACN).

    PubMed

    Jiang, J; Xu, Y; Klaunig, J E

    1998-12-01

    Chronic treatment with acrylonitrile (ACN) has been shown to produce a dose-related increase in glial cell tumors (astrocytomas) in rats. The mechanism(s) for ACN-induced carcinogenicity remains unclear. While ACN has been reported to induce DNA damage in a number of short-term systems, evidence for a genotoxic mechanism of tumor induction is the brain is not strong. Other toxic mechanisms appear to participate in the induction of tumor or induce the astrocytomas solely. In particular, nongenotoxic mechanisms of carcinogen induction have been implicated in this ACN-induced carcinogenic effect in the rat brain. One major pathway of ACN metabolism is through glutathione (GSH) conjugation. Extensive utilization and depletion of GSH, an important intracellular antioxidant, by ACN may lead to cellular oxidative stress. The present study examined the ability of ACN to induce oxidative stress in male Sprague-Dawley rats. Rats were administered ACN at concentrations of 0, 5, 10, 100, or 200 ppm in the drinking water and sampled after 14, 28, or 90 days of continuous treatment. Oxidative DNA damage indicated by the presence of 8-hydroxy-2'-deoxyguanosine (OH8dG) and lipid peroxidation indicated by the presence of malondialdehyde (MDA), a lipid peroxidation product, in rat brains and livers were examined. The levels of reactive oxygen species (ROS) were also determined in different rat tissues. Both the levels of nonenzymatic antioxidants (GSH, vitamin E) and the activities of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase) in rat brains and livers were measured. Increased levels of OH8dG, MDA, and ROS were found in the brains of ACN-treated rats. Decreased levels of GSH and activities of catalase and SOD were also observed in the brains of ACN-treated rats compared to the control group. Interestingly, there were no changes of these indicators of oxidative stress in the livers of ACN-treated rats. Rat liver is not a target for ACN

  4. Transport of 3-hydroxybutyrate by cultured rat brain astrocytes

    SciTech Connect

    McKenna, M.C.; Tildon, J.T.; Stevenson, J.H.; Couto, R.; Caprio, F.J. )

    1990-02-26

    Studies by a number of investigators have shown that 3-hydroxybutyrate is a preferred energy substrate for brain during early development. Since recent studies by the authors group suggest that the utilization of oxidizable substrates by brain may be regulated in part by transport across the plasma membrane, the authors investigated the transport of ({sup 3}H) D- and L-3-hydroxybutyrate and 3-hydroxy-(3-{sup 14}C) butyrate by primary cultures of rat brain astrocytes. The data is consistent with the hypothesis that 3-hydroxybutyrate is taken up into cultured rat brain astrocytes by both diffusion and a carrier mediated transport system, and further support the concept that transport at the cellular level contributes to the regulation of substrate utilization by brain cells.

  5. Non-signalling energy use in the developing rat brain

    PubMed Central

    Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N

    2016-01-01

    Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain. PMID:27170699

  6. Non-signalling energy use in the developing rat brain.

    PubMed

    Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N; Attwell, David

    2017-03-01

    Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.

  7. Effect of carnosine on rats under experimental brain ischemia.

    PubMed

    Gallant, S; Kukley, M; Stvolinsky, S; Bulygina, E; Boldyrev, A

    2000-06-01

    The effect of dietary carnosine on the behavioral and biochemical characteristics of rats under experimental ischemia was studied. Carnosine was shown to improve the animals orientation and learning in "Open Field" and "T-Maze" tests, and this effect was accompanied with an increase in glutamate binding to N-methyl-D-aspartate (NMDA) receptors in brain synaptosomes. Long-term brain ischemia induced by both sides' occlusion of common carotid arteries resulted in 55% mortality of experimental rats, and those who survived were characterized by partial suppression of orientation in T-maze. In the group of rats treated with carnosine, mortality after ischemic attack was decreased (from 55% to 17%) and most of the learning parameters were kept at the pre-ischemic level. Monoamine oxidase B (MAO B) activity in brain of the carnosine treated rats was not changed by ischemia significantly (compared to that of ischemic untreated rats) but NMDA binding to brain synaptosomal membranes being increased by ischemic attack was significantly suppressed and reached the level characteristic of normal brain. The suggestion was made that carnosine possesses a dual effect on NMDA receptors resulting in increase in their amount after long-term treatment but decrease the capacity to bind NMDA after ischemic attack.

  8. SEROTONIN BINDING TO PREPARATIONS FROM RAT BRAIN,

    DTIC Science & Technology

    BRAIN , SEROTONIN, SEROTONIN, OXIDOREDUCTASES, LYSERGIC ACIDS, RESERPINE, CHLORPROMAZINE, ACETYLCHOLINE, FATTY ACIDS, NOREPINEPHRINE, LEARNING, PERMEABILITY, MITOCHONDRIA, MORPHOLOGY(BIOLOGY), DRUGS, PHYSIOLOGY.

  9. Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats.

    PubMed

    Tian, Runfa; Hou, Zonggang; Hao, Shuyu; Wu, Weichuan; Mao, Xiang; Tao, Xiaogang; Lu, Te; Liu, Baiyun

    2016-04-15

    Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.

  10. Proinflammatory cytokines in injured rat brain following perinatal asphyxia.

    PubMed

    Maślińska, Danuta; Laure-Kamionowska, Milena; Kaliszek, Agnieszka; Makarewicz, Dorota

    2002-01-01

    In contrast to astrogliosis, which is common to injuries of the adult CNS, in the developing brain this process is minimal. Reasons postulated for this include the relative immaturity of the immune system and the consequent insufficient production of cytokines to evoke astrogliosis. To explore this hypothesis, the study was undertaken to detect the presence of some proinflammatory cytokines in the injured rat brain following perinatal asphyxia (ischaemia/hypoxia). The localisation of TNF-alpha, IL-15, IL-17 and IL-17 receptors was visualised by means of immunohistochemistry. In numerous neurones of the rat brain, the IL-17 appeared to be constitutively expressed. In the early period of inflammation the IL-15 was produced mainly by the blood cells penetrating the injured brain but later it was synthesised also by reactive astrocytes surrounding brain cysts and forming dense astrogliosis around necrotic brain regions. The direct effect on astrogliosis of other estimated cytokines seems to be negligible. All the results lead to the conclusion that from all cytokines identified in the injured immature rat brain the IL-15 plays the most important role during inflammatory response and participates in the gliosis of reactive astrocytes.

  11. Thermal imaging of brain tumors in a rat glioma model

    NASA Astrophysics Data System (ADS)

    Papaioannou, Thanassis; Thompson, Reid C.; Kateb, Babak; Sorokoumov, Oleg; Grundfest, Warren S.; Black, Keith L.

    2002-05-01

    We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P(greater than)0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

  12. Hydrophilic solute transport across the rat blood-brain barrier

    SciTech Connect

    Lucchesi, K.J.

    1987-01-01

    Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB) was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.

  13. Simultaneous MRI and PET imaging of a rat brain

    NASA Astrophysics Data System (ADS)

    Raylman, Raymond R.; Majewski, Stan; Lemieux, Susan K.; Sendhil Velan, S.; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Zorn, Carl; Marano, Gary D.

    2006-12-01

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  14. System for the measurement of blood flow and oxygenation in tissue applied to neurovascular coupling in brain

    NASA Astrophysics Data System (ADS)

    Kohl-Bareis, Matthias; Leithner, Christoph; Sellien, Heike; Guertler, Roland; Geraskin, Dmitri; Rohrer, Benjamin; Royl, Georg; Dirnagl, Ulrich; Lindauer, Ute

    2005-08-01

    We designed a system incorporating the independent measurement of blood flow and oxygenation of haemoglobin. This is based on laser-Doppler spectroscopy with NIR wavelengths which gives a measure for changes in blood flow or tissue perfusion as well as reflectance spectroscopy in the VIS wavelength range for the calculation of the oxygenated and deoxygenated haemoglobin components. The co-registration of these parameters allows the neurovascular coupling of brain to be investigated. This is demonstrated by recording functional activity of the rat brain during electrical forepaw stimulation.

  15. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat.

    PubMed

    Feng, Yangzheng; Paul, Ian A; LeBlanc, Michael H

    2006-03-31

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

  16. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

    PubMed Central

    Feng, Yangzheng; Paul, Ian A.; LeBlanc, Michael H.

    2011-01-01

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity. PMID:16533659

  17. Isatin, regional distribution in rat brain and tissues.

    PubMed

    Watkins, P; Clow, A; Glover, V; Halket, J; Przyborowska, A; Sandler, M

    1990-01-01

    Isatin has recently been identified in rat tissues and normal human urine, where it forms the major proportion of the endogenous monoamine oxidase inhibitor, tribulin. In this paper, we show that isatin, measured by gas chromatography/mass spectrometry, has a distinct regional distribution in rat tissues, with highest concentrations in seminal vesicles (1.6 ?g/g) and vas deferens (3.4 ?g/g). There was also a discontinuous distribution within rat brain, concentrations being highest in the hippocampus (0.13 ?g/g).

  18. Evaluation of the brain-specific delivery of radioiodinated (iodophenyl)alkyl-substituted amines coupled to a dihydropyridine carrier

    SciTech Connect

    Tedjamulia, M.L.; Srivastava, P.C.; Knapp, F.F. Jr.

    1985-11-01

    To evaluate the potential usefulness of radioiodinated phenylamines attached to dihydropyridine carriers as a means of brain-specific delivery of radiopharmaceuticals, 1-methyl-3-(N-(beta- (4-(125I)iodophenyl)ethyl)carbamoyl)-1,4-dihydropyridine ((125I)-9) and 1-methyl-3-(N-(4-(125I)iodophenyl)carbamoyl)-1,4-dihydropyridine ((125I)-13) have been prepared by dithionite reduction of the corresponding pyridinium precursors, (125I)-8 and (125I)-12, respectively. Formation of 8 involved coupling of (p-aminophenyl)ethylamine with N-succinimidyl (1-methyl-3-pyridinio)formate iodide (4) followed by transformation to the corresponding N-piperidinyl- (6) or (diethylamino)- (7) triazines that were converted to 8 by treatment with HI. Alternatively, 12 was prepared by initial conversion of (4-amino-phenyl)mercuric acetate (10) to 4-iodoaniline (11) by treatment with I2 and then coupling with 4. The radioiodinated quaternary products, 8 and 12, showed low brain uptake and low brain to blood ratios, whereas the dihydropyridine analogues, 9 and 13, showed comparatively good brain uptake and good brain to blood ratios in rats. These data demonstrate that dihydropyridine-coupled radiopharmaceuticals can cross the blood-brain barrier and the technique may be useful for the measurement of cerebral blood perfusion.

  19. Oxidative damage to rat brain in iron and copper overloads.

    PubMed

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  20. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  1. Electrical coupling of astrocytes in rat hippocampal slices under physiological and simulated ischemic conditions.

    PubMed

    Xu, Guangjin; Wang, Wei; Kimelberg, Harold K; Zhou, Min

    2010-03-01

    Mammalian protoplasmic astrocytes are extensively coupled through gap junction channels but the biophysical properties of these channels under physiological and ischemic conditions in situ are not well defined. Using confocal morphometric analysis of biocytin-filled astrocytic syncytia in rat hippocampal CA1 stratum radiatum we found that each astrocyte directly couples, on average, to 11 other astrocytes with a mean interastrocytic distance of 45 microm. Voltage-independent and bidirectional transjunctional currents were always measured between directly coupled astrocyte pairs in dual voltage-clamp recordings, but never from astrocyte-NG2 glia or astrocyte-interneuron pairs. The electrical coupling ratio varied considerably among astrocytes in developing postnatal day 14 rats (P14, 0.5-12.4%, mean = 3.6%), but became more constant in young adult P21 rats (0.18-3.9%, mean = 1.6%), and the coupling ratio declined exponentially with increasing pair distance. Electrical coupling was not affected by short-term oxygen-glucose deprivation (OGD) treatment, but showed delayed inhibition in an acidic extracellular pH of 6.4. Combination of acidic pH (6.4) and OGD, a condition that better represents cerebral ischemia in vivo, accelerated the inhibition of electrical coupling. Our results show that, under physiological conditions, 20.7-24.2% of K(+) induced currents can travel from any astrocytic soma in CA1 stratum radiatum to the gap junctions of the nearest neighbor astrocytes, but this should be severely inhibited as a consequence of the OGD and acidosis seen in the ischemic brain.

  2. Demonstration of endogenous imipramine like material in rat brain

    SciTech Connect

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  3. Waxholm Space atlas of the Sprague Dawley rat brain.

    PubMed

    Papp, Eszter A; Leergaard, Trygve B; Calabrese, Evan; Johnson, G Allan; Bjaalie, Jan G

    2014-08-15

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 μm isotropic voxels for the MRI volume and 78 μm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multi-level data integration and analysis across reference spaces.

  4. EVALUATION OF PERFLUOROOCTANE SULFONATE IN THE RAT BRAIN

    EPA Science Inventory

    Perfluorooctane Sulfonate (PFOS) is an environmentally persistent chemical that has been detected in humans and wildlife. PFOS is primarily distributed in liver and blood. The current study evaluated the level of PFOS in the adult and neonatal rat brain and determined whether t...

  5. Experimental induction of corpora amylacea in adult rat brain.

    PubMed

    Schipper, H M

    1998-10-01

    Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

  6. Thyroid insufficiency in developing rat brain: A genomic analysis.

    EPA Science Inventory

    Thyroid Insufficiency in the Developing Rat Brain: A Genomic Analysis. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption (ED) is an area of major concern in environmental neurotoxicity. Severe deficits in thyroid hormone (TH) levels have bee...

  7. Autoradiographic localization of relaxin binding sites in rat brain

    SciTech Connect

    Osheroff, P.L.; Phillips, H.S. )

    1991-08-01

    Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, the authors have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, they describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. They conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.

  8. FACS purification of immunolabeled cell types from adult rat brain.

    PubMed

    Guez-Barber, Danielle; Fanous, Sanya; Harvey, Brandon K; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G; Picciotto, Marina R; Hope, Bruce T

    2012-01-15

    Molecular analysis of brain tissue is greatly complicated by having many different classes of neurons and glia interspersed throughout the brain. Fluorescence-activated cell sorting (FACS) has been used to purify selected cell types from brain tissue. However, its use has been limited to brain tissue from embryos or transgenic mice with promoter-driven reporter genes. To overcome these limitations, we developed a FACS procedure for dissociating intact cell bodies from adult wild-type rat brains and sorting them using commercially available antibodies against intracellular and extracellular proteins. As an example, we isolated neurons using a NeuN antibody and confirmed their identity using microarray and real time PCR of mRNA from the sorted cells. Our FACS procedure allows rapid, high-throughput, quantitative assays of molecular alterations in identified cell types with widespread applications in neuroscience.

  9. The First in Vivo Observation of 13C- 15N Coupling in Mammalian Brain

    NASA Astrophysics Data System (ADS)

    Kanamori, Keiko; Ross, Brian D.

    2001-12-01

    [5-13C,15N]Glutamine, with 1J(13C-15N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by 13C MRS at 4.7 T. The brain [5-13C]glutamine peak consisted of the doublet from [5-13C,15N]glutamine and the center [5-13C,14N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-13C,15N]glutamine was monitored in vivo with a time resolution of 20-35 min. This [5-13C,15N]glutamine was formed by glial uptake of released neurotransmitter [5-13C]glutamate and its reaction with 15NH3 catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively13C-enriched by intravenous [2,5-13C]glucose infusion to 13C-label whole-brain glutamate C5, followed by [12C]glucose infusion to chase 13C from the small and rapidly turning-over glial glutamate pool, leaving 13C mainly in the neurotransmitter [5-13C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-13C,15N]glutamine arises from a coupling between 13C of neuronal origin and 15N of glial origin. Measurement of the rate of brain [5-13C,15N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.

  10. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  11. Perinatal manganese exposure and hydroxyl radical formation in rat brain.

    PubMed

    Bałasz, Michał; Szkilnik, Ryszard; Brus, Ryszard; Malinowska-Borowska, Jolanta; Kasperczyk, Sławomir; Nowak, Damian; Kostrzewa, Richard M; Nowak, Przemysław

    2015-01-01

    The present study was designed to investigate the role of pre- and postnatal manganese (Mn) exposure on hydroxyl radical (HO(•)) formation in the brains of dopamine (DA) partially denervated rats (Parkinsonian rats). Wistar rats were given tap water containing 10,000 ppm manganese chloride during the duration of pregnancy and until the time of weaning. Control rat dams consumed tap water without added Mn. Three days after birth, rats of both groups were treated with 6-hydroxydopamine at one of three doses (15, 30, or 67 µg, intraventricular on each side), or saline vehicle. We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy. In neonates, the major organs that accumulated Mn were the femoral bone and liver. However, Mn was not elevated in tissues in adulthood. To determine the possible effect on generation of the reactive species, HO(•) in Mn-induced neurotoxicity, we analyzed the contents of 2.3- and 2.5-dihydroxybenzoic acid (spin trap products of salicylate; HO(•) being an index of in vivo HO(•) generation), as well as antioxidant enzyme activities of superoxide dismutase (SOD) isoenzymes and glutathione S-transferase (GST). 6-OHDA-depletion of DA produced enhanced HO(•) formation in the brain tissue of newborn and adulthood rats that had been exposed to Mn, and the latter effect did not depend on the extent of DA denervation. Additionally, the extraneuronal, microdialysate, content of HO(•) in neostriatum was likewise elevated in 6-OHDA-lesioned rats. Interestingly, there was no difference in extraneuronal HO(•) formation in the neostriatum of Mn-exposed versus control rats. In summary, findings in this study indicate that Mn crosses the placenta but in contrast to other heavy metals, Mn is not deposited long term in tissues. Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in

  12. GABA(B) receptors: altered coupling to G-proteins in rats sensitized to amphetamine.

    PubMed

    Zhang, K; Tarazi, F I; Campbell, A; Baldessarini, R J

    2000-01-01

    Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of both neurotransmitters is influenced by GABA(B) metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABA(B) receptors were examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [(3)H]baclofen binding and baclofen-mediated [(35)S]GTP gamma S binding. Repeated treatment with (+)-amphetamine (5mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1mg/kg) at 14 days, but not one day, later. GABA(B) receptor density was not altered at either time. Baclofen-mediated [(35)S]GTP gamma S binding, however, was selectively augmented in the prefrontal cortex and attenuated in the nucleus accumbens at 14 days, but not one day, after amphetamine treatment. Changes in GABA(B) receptor coupling to G-proteins in rats sensitized to amphetamine, but not in similarly treated but unsensitized rats, lead us to suggest that altered GABA(B) receptor functioning may contribute to the expression of amphetamine-induced behavioral sensitization.

  13. Inducible Gene Manipulations in Brain Serotonergic Neurons of Transgenic Rats

    PubMed Central

    Tews, Björn; Bartsch, Dusan

    2011-01-01

    The serotonergic (5-HT) system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP), in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system. PMID:22140568

  14. Anesthesia-induced neurodegeneration in fetal rat brains

    PubMed Central

    Wang, Shouping; Peretich, Kelly; Zhao, Yifan; Liang, Ge; Meng, Qingcheng; Wei, Huafeng

    2011-01-01

    Summary We investigated the extent of isoflurane induced neurodegeneration on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 21 were divided into three experimental groups. Rats in the control group spontaneously breathed 100% oxygen for one hour. Rats in the treatment groups breathed either 1.3% or 3% isoflurane in 100% oxygen through an endotracheal tube with mechanical ventilation for one hour. Rat pups were delivered by Caesarian section six hours after treatment and fetal blood was sampled from the left ventricle of each fetal heart and evaluated for S100β. Fetal brains were then evaluated for apoptosis using caspase-3 immunohistochemistry in the CA1 region of the hippocampus and the retrosplenial cortex (RS). The 3% isoflurane treatment group showed significantly higher levels of S100β levels and significantly increased average densities of total caspase-3 positive cells in the CA1 hippocampus and RS cortex as compared to the control and 1.3% isoflurane groups. There were no differences in S100β levels or densities of caspase-3 positive cells between the control and 1.3% isoflurane groups. Isoflurane at a concentration of 3% for one hour increased neurodegeneration in the hippocampal CA1 area and the retrosplenial cortex in the developing brain of fetal rats. PMID:20016413

  15. Pharmacological modulation of blood-brain barrier increases permeability of doxorubicin into the rat brain.

    PubMed

    Sardi, Iacopo; la Marca, Giancarlo; Cardellicchio, Stefania; Giunti, Laura; Malvagia, Sabrina; Genitori, Lorenzo; Massimino, Maura; de Martino, Maurizio; Giovannini, Maria G

    2013-01-01

    Our group recently demonstrated in a rat model that pretreatment with morphine facilitates doxorubicin delivery to the brain in the absence of signs of increased acute systemic toxicity. Morphine and other drugs such as dexamethasone or ondansetron seem to inhibit MDR proteins localized on blood-brain barrier, neurons and glial cells increasing the access of doxorubicin to the brain by efflux transporters competition. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine dexamethasone or ondansetron pretreatment, to allow doxorubicin accumulation into the brain in a rodent model. Rats were pretreated with morphine (10 mg/kg, i.p.), dexamethasone (2 mg/kg, i.p.) or ondansetron (2 mg/kg, i.p.) before injection of doxorubicin (12 mg/kg, i.p.). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine (P < 0.001) or ondansetron (P < 0.05) than in control tissues. The concentration of doxorubicin was significantly higher in cerebral hemispheres and brainstem (P < 0.05) but not in cerebellum of rats pretreated with dexamethasone than in control tissues. Pretreatment with any of these drugs did not increase LDH activity or lipid peroxidation compared to controls. Our data suggest that morphine, dexamethasone or ondansetron pretreatment is able to allow doxorubicin penetration inside the brain by modulating the BBB. This effect is not associated with acute cardiac or renal toxicity. This finding might provide the rationale for clinical applications in the treatment of refractory brain tumors and pave the way to novel applications of active but currently inapplicable chemotherapeutic drugs.

  16. Neurovascular coupling: in vivo optical techniques for functional brain imaging

    PubMed Central

    2013-01-01

    Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology. PMID:23631798

  17. Neurovascular coupling: in vivo optical techniques for functional brain imaging.

    PubMed

    Liao, Lun-De; Tsytsarev, Vassiliy; Delgado-Martínez, Ignacio; Li, Meng-Lin; Erzurumlu, Reha; Vipin, Ashwati; Orellana, Josue; Lin, Yan-Ren; Lai, Hsin-Yi; Chen, You-Yin; Thakor, Nitish V

    2013-04-30

    Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology.

  18. Rat umbilical cord blood cells attenuate hypoxic–ischemic brain injury in neonatal rats

    PubMed Central

    Nakanishi, Keiko; Sato, Yoshiaki; Mizutani, Yuka; Ito, Miharu; Hirakawa, Akihiro; Higashi, Yujiro

    2017-01-01

    Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells. PMID:28281676

  19. Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat.

    PubMed

    Serres, Sébastien; Bezancon, Eric; Franconi, Jean-Michel; Merle, Michel

    2007-06-01

    The occurrence of pyruvate recycling in the rat brain was studied in either pentobarbital anesthetized animals or awake animals receiving a light analgesic dose of morphine, which were infused with either [1-13C]glucose + acetate or glucose + [2-13C]acetate for various periods of time. Metabolite enrichments in the brain, blood and the liver were determined from NMR analyses of tissue extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain of both the anesthetized and awake animals, as well as from lactate and alanine enrichments as from glutamate isotopomer composition, but only after infusion of glucose + [2-13C]acetate. (ii) Brain glucose was labelled from [2-13C]acetate at the same level in anaesthetized and awake rats (approximately 4%). Comparing its enrichment with that of blood and liver glucose indicated that brain glucose labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13C-13C coupling in the brain, blood and the liver confirmed that brain glucose could be labelled in the liver through the activities of both pyruvate recycling and gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4-C5 coupling, a marker of pyruvate recycling when starting from [2-13C]acetate, were lower than those of brain glucose labelling from hepatic metabolism. (v) The evaluation of the contributions of glucose and acetate to glutamate metabolism revealed that more than 60% of brain glutamate was synthesized from glucose whereas only 7% was from acetate and that glutamate C4-C5 coupling was mainly due to the metabolism of glucose labelled through hepatic gluconeogenesis. All these results indicate that, under the present conditions, the pyruvate recycling observed through the labelling of brain metabolites mainly originates from peripheral metabolism.

  20. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    PubMed Central

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  1. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    PubMed

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  2. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  3. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    PubMed

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  4. Advanced in vitro approach to study neurovascular coupling mechanisms in the brain microcirculation

    PubMed Central

    Kim, Ki Jung; Filosa, Jessica A

    2012-01-01

    An understanding of the signalling events underlying neurovascular coupling mechanisms in the brain is a crucial step in the development of novel therapeutic approaches for the treatment of cerebrovascular-associated disorders. In this study we present an enhanced in vitro brain slice preparation from male Wistar rat cortical slices that incorporates haemodynamic variables (flow and pressure) into parenchymal arterioles resulting in the development of myogenic tone (28% from maximum dilatation). Moreover, we characterized flow-induced vascular responses, resulting in various degrees of vasoconstrictions and the response to 10 mm K+ or astrocytic activation with the mGluR agonist, t-ACPD (100 μm), resulting in vasodilatations of 33.6 ± 4.7% and 38.6 ± 4.6%, respectively. Using fluorescence recovery, we determined perfusate velocity to calculate diameter changes under different experimental pH conditions. Using this approach, we demonstrate no significant differences between diameter changes measured using video microscopy or predicted from the velocity values obtained using fluorescence recovery after photobleaching. The model is further validated by demonstrating our ability to cannulate arterioles in two brain regions (cortex and supraoptic nucleus of the hypothalamus). Altogether, we believe this is the first study demonstrating successful cannulation and perfusion of parenchymal arterioles while monitoring/estimating luminal diameter and pressure under conditions where flow rates are controlled. PMID:22310311

  5. Effects of treating old rats with an aqueous Agaricus blazei extract on oxidative and functional parameters of the brain tissue and brain mitochondria.

    PubMed

    de Sá-Nakanishi, Anacharis B; Soares, Andréia A; de Oliveira, Andrea Luiza; Comar, Jurandir Fernando; Peralta, Rosane M; Bracht, Adelar

    2014-01-01

    Dysfunction of the mitochondrial respiratory chain and increased oxidative stress is a striking phenomenon in the brain of aged individuals. For this reason there has been a constant search for drugs and natural products able to prevent or at least to mitigate these problems. In the present study the effects of an aqueous extract of Agaricus blazei, a medicinal mushroom, on the oxidative state and on the functionality of mitochondria from the brain of old rats (21 months) were conducted. The extract was administered intragastrically during 21 days at doses of 200 mg/kg. The administration of the A. blazei extract was protective to the brain of old rats against oxidative stress by decreasing the lipid peroxidation levels and the reactive oxygen species content and by increasing the nonenzymic and enzymic antioxidant capacities. Administration of the A. blazei extract also increased the activity of several mitochondrial respiratory enzymes and, depending on the substrate, the mitochondrial coupled respiration.

  6. Effects of Treating Old Rats with an Aqueous Agaricus blazei Extract on Oxidative and Functional Parameters of the Brain Tissue and Brain Mitochondria

    PubMed Central

    de Sá-Nakanishi, Anacharis B.; Soares, Andréia A.; de Oliveira, Andrea Luiza; Fernando Comar, Jurandir; Peralta, Rosane M.; Bracht, Adelar

    2014-01-01

    Dysfunction of the mitochondrial respiratory chain and increased oxidative stress is a striking phenomenon in the brain of aged individuals. For this reason there has been a constant search for drugs and natural products able to prevent or at least to mitigate these problems. In the present study the effects of an aqueous extract of Agaricus blazei, a medicinal mushroom, on the oxidative state and on the functionality of mitochondria from the brain of old rats (21 months) were conducted. The extract was administered intragastrically during 21 days at doses of 200 mg/kg. The administration of the A. blazei extract was protective to the brain of old rats against oxidative stress by decreasing the lipid peroxidation levels and the reactive oxygen species content and by increasing the nonenzymic and enzymic antioxidant capacities. Administration of the A. blazei extract also increased the activity of several mitochondrial respiratory enzymes and, depending on the substrate, the mitochondrial coupled respiration. PMID:24876914

  7. Alterations of amino Acid level in depressed rat brain.

    PubMed

    Yang, Pei; Li, Xuechun; Ni, Jian; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-10-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

  8. Human and rat brain lipofuscin proteome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of an autofluorescent pigment called lipofuscin in neurons is an invariable hallmark of brain aging. So far, this material has been considered to be waste material without particular relevance for cellular pathology. However, two lines of evidence argue that lipofuscin may have yet ...

  9. Regional development of glutamate dehydrogenase in the rat brain.

    PubMed

    Leong, S F; Clark, J B

    1984-07-01

    The development of glutamate dehydrogenase enzyme activity in rat brain regions has been followed from the late foetal stage to the adult and through to the aged (greater than 2 years) adult. In the adult brain the enzyme activity was greatest in the medulla oblongata and pons greater than midbrain = hypothalamus greater than cerebellum = striatum = cortex. In the aged adult brain, glutamate dehydrogenase activity was significantly lower in the medulla oblongata and pons when compared to the 90-day-old adult value, but not in other regions. The enzyme-specific activity of nonsynaptic (free) mitochondria purified from the medulla oblongata and pons of 90-day-old animals was about twice that of mitochondria purified from the striatum and the cortex. The specific activity of the enzyme in synaptic mitochondria purified from the above three brain regions, however, remained almost constant.

  10. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    SciTech Connect

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. )

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  11. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    PubMed

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  12. Determination of boron distribution in rat's brain, kidney and liver.

    PubMed

    Pazirandeh, Ali; Jameie, Behnam; Zargar, Maysam

    2009-07-01

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  13. Differential expression of sirtuins in the aging rat brain

    PubMed Central

    Braidy, Nady; Poljak, Anne; Grant, Ross; Jayasena, Tharusha; Mansour, Hussein; Chan-Ling, Tailoi; Smythe, George; Sachdev, Perminder; Guillemin, Gilles J.

    2015-01-01

    Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of “physiologically” aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging. PMID:26005404

  14. Rat brains also have a default mode network

    PubMed Central

    Lu, Hanbing; Zou, Qihong; Gu, Hong; Raichle, Marcus E.; Stein, Elliot A.; Yang, Yihong

    2012-01-01

    The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function(s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies. PMID:22355129

  15. HEPES prevents edema in rat brain slices.

    PubMed

    MacGregor, D G; Chesler, M; Rice, M E

    2001-05-11

    Brain slices gain water when maintained in bicarbonate-buffered artificial cerebro-spinal fluid (ACSF) at 35 degrees C. We previously showed that this edema is linked to glutamate receptor activation and oxidative stress. An additional factor that may contribute to swelling is acidosis, which arises from high CO2 tension in brain slices. To examine the role of acidosis in slice edema, we added N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to osmotically balanced ACSF (HEPES-ACSF), thereby increasing buffering capacity beyond that provided by bicarbonate/CO2. Water gain was markedly inhibited in HEPES-ACSF. After 3 h incubation in HEPES-ACSF at 35 degrees C, water gain was limited to that of fresh slices after 1 h recovery in ACSF at room temperature. The effect of HEPES in decreasing slice water gain was concentration dependent from 0.3 to 20 mM. The inhibition of water gain by HEPES suggests that tissue acidosis is a contributing factor in brain slice edema.

  16. Cloning and expression of a rat brain GABA transporter

    SciTech Connect

    Guastella, J.; Czyzyk, L.; Davidson, N.; Lester, H.A. ); Nelson, N.; Nelson, H.; Miedel, M.C. ); Keynan, S.; Kanner, B.I. )

    1990-09-14

    A complementary DNA clone (designated GAT-1) encoding a transporter for the neurotransmitter {gamma}-aminobutyric acid (GABA) has been isolated from rat brain, and its functional properties have been examined in Xenopus oocytes. Oocytes injected with GAT-1 synthetic messenger RNA accumulated ({sup 3}H)GABA to levels above control values. The transporter encoded by GAT-1 has a high affinity for GABA, is sodium- and chloride-dependent, and is pharmacologically similar to neuronal GABA transporters. The GAT-1 protein shares antigenic determinants with a native rat brain GABA transporter. The nucleotide sequence of GAT-1 predicts a protein of 599 amino acids with a molecular weight of 67 kilodaltons. Hydropathy analysis of the deduced protein suggests multiple transmembrane regions, a feature shared by several cloned transporters; however, database searches indicate that GAT-1 is not homologous to any previously identified proteins. Therefore, GAT-1 appears to be a member of a previously uncharacterized family of transport molecules.

  17. Neuroprotection of Selective Brain Cooling After Penetrating Ballistic-like Brain Injury in Rats.

    PubMed

    Wei, Guo; Lu, Xi-Chun M; Shear, Deborah A; Yang, Xiaofang; Tortella, Frank C

    2011-01-01

    Induced hypothermia has been reported to provide neuroprotection against traumatic brain injury. We recently developed a novel method of selective brain cooling (SBC) and demonstrated its safety and neuroprotection efficacy in a rat model of ischemic brain injury. The primary focus of the current study was to evaluate the potential neuroprotective efficacy of SBC in a rat model of penetrating ballistic-like brain injury (PBBI) with a particular focus on the acute cerebral pathophysiology, neurofunction, and cognition. SBC (34°C) was induced immediately after PBBI, and maintained for 2 hours, followed by a spontaneous re-warming. Intracranial pressure (ICP) and regional cerebral blood flow were monitored continuously for 3 hours, and the ICP was measured again at 24 hours postinjury. Brain swelling, blood-brain barrier permeability, intracerebral hemorrhage, lesion size, and neurological status were assessed at 24 hours postinjury. Cognitive abilities were evaluated in a Morris water maze task at 12-16 days postinjury. Results showed that SBC significantly attenuated PBBI-induced elevation of ICP (PBBI = 33.2 ± 10.4; PBBI + SBC = 18.8 ± 6.7 mmHg) and reduced brain swelling, blood-brain barrier leakage, intracerebral hemorrhage, and lesion volume by 40%-45% for each matrix, and significantly improved neurologic function. However, these acute neuroprotective benefits of SBC did not translate into improved cognitive performance in the Morris water maze task. These results indicate that 34°C SBC is effective in protecting against acute brain damage and related neurological dysfunction. Further studies are required to establish the optimal treatment conditions (i.e., duration of cooling and/or combined therapeutic approaches) needed to achieve significant neurocognitive benefits.

  18. [Effect of phenibut on interhemispheric transmission in the rat brain].

    PubMed

    Borodkina, L E; Molodavkin, G M; Tiurenkov, I N

    2009-01-01

    Effects of the nootropic drug phenibut on the transcallosal potential amplitude in the sensomotor brain cortex have been studied in rats. It is established that a single administration of phenibut in a dose of 25 mg/kg (i.p.) increases the transcallosal response amplitude, thus improving the interhemispheric transmission. This effect, being an objective evidence of the nootrope activity, confirms the drug status and corroborates the positive action of phenibut on the learning and memory processes.

  19. Identification of rat brain opioid (enkephalin) receptor by photoaffinity labeling

    SciTech Connect

    Yeung, C.W.

    1986-01-01

    A photoreactive, radioactive enkephalin derivative was prepared and purified by high performance liquid chromatography. Rat brain and spinal cord plasma membranes were incubated with this radioiodinated photoprobe and were subsequently photolysed. Autoradiography of the sodium dodecyl sulfate gel electrophoresis of the solubilized and reduced membranes showed that a protein having an apparent molecular weight of 46,000 daltons was specifically labeled, suggesting that this protein may be the opioid (enkephalin) receptor.

  20. Oxidative changes in brain of aniline-exposed rats

    SciTech Connect

    Kakkar, P.; Awasthi, S.; Viswanathan, P.N. )

    1992-10-01

    Oxidative stress in rat cerebellum, cortex and brain stem after a short-term high-dose exposure to aniline vapors under conditions akin to those after major chemical accidents, was studied. Significant increases in superoxide dismutase isozyme activities and formation of thiobarbituric acid reactive material along with depletion of ascorbic acid and non-protein sulfhydryl content suggest impairment of antioxidant defenses 24 h after single exposure to 15,302 ppm aniline vapors for 10 min.

  1. Development of specificity and stereoselectivity of rat brain dopamine receptors.

    PubMed

    Miller, J C; Friedhoff, A J

    1986-01-01

    Prenatal exposure to the neuroleptic haloperidol has been reported to produce an enduring decrement in the number of dopamine D2 receptors in rat striatum and a persistent diminution of a dopamine dependent behavior, stereotypy. The ontogeny of rat brain dopamine binding sites has been studied in terms of the kinetic properties and phenotypic specificity in rat fetal brain through early postnatal development. Sites showing some properties of the D2 binding site can be found prior to gestational day (GD) 18, can be labeled with [3H]dopamine or [3H]spiroperidol and can be displaced with dopaminergic agonists and antagonists. Saturation kinetics for specific [3H]spiroperidol has previously been found to occur on or about GD 18. It is of interest that the critical period for the prenatal effect of haloperidol to reduce striatal D2 binding sites, GD's 15-18, coincides with the period during which dopamine binding sites lack true specificity, but can be labeled with dopaminergic ligands. In these experiments the development of stereoselectivity of brain dopamine binding sites has been examined. When rat mothers were given either the neuroleptic (+)-butaclamol or its therapeutically inactive isomer (-)-butaclamol during the critical period GD's 15-18, the number of [3H]spiroperidol binding sites in striata of offspring was significantly reduced by both stereoisomers. This is in marked contrast to the postnatal treatment effect by a neuroleptic in which upregulation of striatal D2 binding sites occurs only by treatment with the therapeutically active isomer (+)-butaclamol. In vitro studies of the direct effect of the stereoisomers of butaclamol indicate that the recognition sites detected during fetal brain development with [3H]spiroperidol do not distinguish between the isomers of butaclamol.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    SciTech Connect

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  3. Gelation and fodrin purification from rat brain extracts.

    PubMed

    Levilliers, N; Péron-Renner, M; Coffe, G; Pudles, J

    1986-06-03

    Extracts from rat brain tissue have been shown to give rise to a gel which exhibits the following features. It is mainly enriched in actin and in a high-molecular-weight protein with polypeptide chains of 235 and 240 kDa, which we identified as fodrin. Tubulin is also a major component of the gel but it appears to be trapped non-specifically during the gelation process. Gelation is pH-, ionic strength- and Ca2+-concentration-dependent, and is optimal under the conditions which promote the interaction between polymerized actin and fodrin. In a similar way to that described for the purification of rat brain actin (Levilliers, N., Péron-Renner, M., Coffe, G. and Pudles, J. (1984) Biochimie 66, 531-537), we used the gelation system as a selective means of recovering fodrin from the mixture of a low-ionic-strength extract from whole rat brain and a high-ionic-strength extract of the particulate fraction. From this gel, fodrin was purified with a good yield by a simple procedure involving gel dissociation in 0.5 M KCl and depolymerization in 0.7 M KI, Bio-Gel A-15m chromatography, followed by ammonium sulfate precipitation.

  4. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  5. Brain oxidative stress induced by obstructive jaundice in rats.

    PubMed

    Chroni, Elisabeth; Patsoukis, Nikolaos; Karageorgos, Nikolaos; Konstantinou, Dimitris; Georgiou, Christos

    2006-02-01

    The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

  6. Intrinsic optical signals of brains in rats during loss of tissue viability: effect of brain temperature

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Kikuchi, Makoto

    2007-07-01

    Noninvasive, real-time monitoring of brain tissue viability is crucial for the patients with stroke, traumatic brain injury, etc. For this purpose, measurement of intrinsic optical signal (IOS) is attractive because it can provide direct information about the viability of brain tissue noninvasively. We performed simultaneous measurements of IOSs that are related to morphological characteristics, i.e., light scattering, and energy metabolism for rat brains during saline infusion as a model with temporal loss of brain tissue viability. The results showed that the scattering signal was steady in an initial phase but showed a drastic, triphasic change in a certain range of infusion time, during which the reduction of CuA in cytochrome c oxidase started and proceeded rapidly. The start time of triphasic scattering change was delayed for about 100 s by lowering brain temperature from 29°C to 24°C, demonstrating the optical detection of cerebroprotection effect by brain cooling. Electron microscopic observation showed morphological changes of dendrite and mitochondria in the cortical surface tissue after the triphasic scattering change, which was thought to be associated with the change in light scattering we observed. These findings suggest that the simultaneous measurement of the intrinsic optical signals related to morphological characteristics and energy metabolism is useful for monitoring tissue viability in brain.

  7. Encoding-based brain-computer interface controlled by non-motor area of rat brain.

    PubMed

    Lang, Yiran; Du, Ping; Shin, Hyung-Cheul

    2011-09-01

    As the needs of disabled patients are increasingly recognized in society, researchers have begun to use single neuron activity to construct brain-computer interfaces (BCI), designed to facilitate the daily lives of individuals with physical disabilities. BCI systems typically allow users to control computer programs or external devices via signals produced in the motor or pre-motor areas of the brain, rather than producing actual motor movements. However, impairments in these brain areas can hinder the application of BCI. The current paper demonstrates the feasibility of a one-dimensional (1D) machine controlled by rat prefrontal cortex (PFC) neurons using an encoding method. In this novel system, rats are able to quench thirst by varying neuronal firing rate in the PFC to manipulate a water dish that can rotate in 1D. The results revealed that control commands generated by an appropriate firing frequency in rat PFC exhibited performance improvements with practice, indicated by increasing water-drinking duration and frequency. These results demonstrated that it is possible for rats to understand an encoding-based BCI system and control a 1D machine using PFC activity to obtain reward.

  8. Outer brain barriers in rat and human development

    PubMed Central

    Brøchner, Christian B.; Holst, Camilla B.; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6–21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer. PMID:25852456

  9. A 3D digital map of rat brain.

    PubMed

    Toga, A W; Santori, E M; Hazani, R; Ambach, K

    1995-01-01

    A three dimensional (3D) computerized map of rat brain anatomy created with digital imaging techniques is described. Six male Sprague-Dawley rats, weighing 270-320 g, were used in the generation of this atlas. Their heads were frozen, and closely spaced cryosectional images were digitally captured. Each serial data set was organized into a digital volume, reoriented into a flat skull position, and brought into register with each other. A volume representative of the group following registration was chosen based on its anatomic correspondence with the other specimens as measured by image correlation coefficients and landmark matching. Mean positions of lambda, bregma, and the interaural plane of the group within the common coordinate system were used to transform the representative volume into a 3D map of rat neuroanatomy. images reconstructed from this 3D map are available to the public via Internet with an anonymous file transfer protocol (FTP) and World Wide Web. A complete description of the digital map is provided in a comprehensive set of sagittal planes (up to 0.031 mm spacing) containing stereotaxic reference grids. Sets of coronal and horizontal planes, resampled at the same increment, also are included. Specific anatomic features are identified in a second collection of images. Stylized anatomic boundaries and structural labels were incorporated into selected orthogonal planes. Electronic sharing and interactive use are benefits afforded by a digital format, but the foremost advantage of this 3D map is its whole brain integrated representation of rat in situ neuroanatomy.

  10. Photoacoustic imaging for transvascular drug delivery to the rat brain

    NASA Astrophysics Data System (ADS)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  11. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain.

    PubMed

    Kobayashi, Megumi Sugahara; Asai, Satoshi; Ishikawa, Koichi; Nishida, Yayoi; Nagata, Toshihito; Takahashi, Yasuo

    2008-06-01

    Mild to moderate differences in brain temperature are known to greatly affect the outcome of cerebral ischemia. The impact of brain temperature on ischemic disorders has been mainly evaluated through pathological analysis. However, no comprehensive analyses have been conducted at the gene expression level. Using a high-density oligonucleotide microarray, we screened 24000 genes in the hippocampus under hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (39 degrees C) conditions in a rat ischemia-reperfusion model. When the ischemic group at each intra-ischemic brain temperature was compared to a sham-operated control group, genes whose expression levels changed more than three-fold with statistical significance could be detected. In our screening condition, thirty-three genes (some of them novel) were obtained after screening, and extensive functional surveys and literature reviews were subsequently performed. In the hypothermic condition, many neuroprotective factor genes were obtained, whereas cell death- and cell damage-associated genes were detected as the brain temperature increased. At all intra-ischemic brain temperatures, multiple molecular chaperone genes were obtained. The finding that intra-ischemic brain temperature affects the expression level of many genes related to neuroprotection or neurotoxicity coincides with the different pathological outcomes at different brain temperatures, demonstrating the utility of the genetic approach.

  12. Modifications of 5-HT4 receptor expression in rat brain during memory consolidation.

    PubMed

    Manuel-Apolinar, L; Rocha, L; Pascoe, D; Castillo, E; Castillo, C; Meneses, A

    2005-04-25

    Pharmacological evidence indicates a specific role of 5-HT(4) receptors on memory function. These receptors are members of G-protein-coupled 7-transmembrane domain receptor superfamily, are positively coupled to adenylyl cyclase, and are heterogeneously located in some structures important for memory, such as the hippocampus and cortical regions. To further clarify 5-HT(4) receptors' role in memory, the expression of these receptors in passive (P3) untrained and autoshaping (A3) trained (3 sessions) adult (3 months) and old (P9 or A9; 9 months) male rats was determined by autoradiography. Adult trained (A3) rats showed a better memory respect to old trained (A9). Using [(3)H] GR113808 as ligand (0.2 nM specific activity 81 Ci/mmol) for 5-HT(4) receptor expression, 29 brain areas were analyzed, 16 areas of A3 and 17 of A9 animals displayed significant changes. The medial mammillary nucleus of A3 group showed diminished 5-HT(4) receptor expression, and in other 15 brain areas of A3 or 10 of A9 animals, 5-HT(4) receptors were increased. Thus, for A3 rats, 5-HT(4) receptors were augmented in olfactory lobule, caudate putamen, fundus striatum, CA2, retrosplenial, frontal, temporal, occipital, and cingulate cortex. Also, 5-HT(4) receptors were increased in olfactory tubercule, hippocampal CA1, parietal, piriform, and cingulate cortex of A9. However, hippocampal CA2 and CA3 areas, and frontal, parietal, and temporal cortex of A9 rats, expressed less 5-HT(4) receptors. These findings suggest that serotonergic activity, via 5-HT(4) receptors in hippocampal, striatum, and cortical areas, mediates memory function and provides further evidence for a complex and regionally specific regulation over 5-HT receptor expression during memory formation.

  13. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    PubMed

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-02-20

    Δ(9)-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [(18)F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of < 1 ng/ml (injected dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.

  14. Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene

    PubMed Central

    Stefaniuk, Marzena; Gualda, Emilio J.; Pawlowska, Monika; Legutko, Diana; Matryba, Paweł; Koza, Paulina; Konopka, Witold; Owczarek, Dorota; Wawrzyniak, Marcin; Loza-Alvarez, Pablo; Kaczmarek, Leszek

    2016-01-01

    Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior over passive CLARITY and CUBIC methods. Finally, we demonstrate efficient imaging of the rat brain using light-sheet fluorescence microscopy. PMID:27312902

  15. Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats.

    PubMed

    Neth, Katharina; Lucio, Marianna; Walker, Alesia; Zorn, Julia; Schmitt-Kopplin, Philippe; Michalke, Bernhard

    2015-01-01

    Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography--inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization--ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism.

  16. Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats

    PubMed Central

    Neth, Katharina; Lucio, Marianna; Walker, Alesia; Zorn, Julia; Schmitt-Kopplin, Philippe; Michalke, Bernhard

    2015-01-01

    Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography—inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization—ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism. PMID:26383269

  17. A simple implantation method for flexible, multisite microelectrodes into rat brains

    PubMed Central

    Richter, Anja; Xie, Yijing; Schumacher, Anett; Löffler, Susanne; Kirch, Robert D.; Al-Hasani, Jaafar; Rapoport, Daniel H.; Kruse, Charli; Moser, Andreas; Tronnier, Volker; Danner, Sandra; Hofmann, Ulrich G.

    2013-01-01

    A long term functional and reliable coupling between neural tissue and implanted microelectrodes is the key issue in acquiring neural electrophysiological signals or therapeutically excite neural tissue. The currently often used rigid micro-electrodes are thought to cause a severe foreign body reaction resulting in a thick glial scar and consequently a poor tissue-electrode coupling in the chronic phase. We hypothesize, that this adverse effect might be remedied by probes compliant to the soft brain tissue, i.e., replacing rigid electrodes by flexible ones. Unfortunately, this flexibility comes at the price of a low stiffness, which makes targeted low trauma implantation very challenging. In this study, we demonstrate an adaptable and simple method to implant extremely flexible microprobes even to deep areas of rat's brain. Implantation of flexible probes is achieved by rod supported stereotactic insertion fostered by a hydrogel (2% agarose in PBS) cushion on the exposed skull. We were thus able to implant very flexible micro-probes in 70 rats as deep as the rodent's subthalamic nucleus. This work describes in detail the procedures and steps needed for minimal invasive, but reliable implantation of flexible probes. PMID:23898266

  18. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood-brain barrier.

    PubMed

    Wang, Xiang; Liu, Ping; Yang, Weixiao; Li, Lu; Li, Peijing; Liu, Zheng; Zhuo, Zhongxiong; Gao, Yunhua

    2014-01-01

    Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%± 0.86%, and their size (2.64 ± 0.93 μm in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood-brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3 ± 2.4 μg/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6 ± 2.2 μg/g) > MTX alone (6.97 ± 0.75 μg/g) > MTX-liposome-coupled microbubbles (2.92 ± 0.39 μg/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (P<0.01). These results suggest that MTX-liposome-coupled microbubbles may hold great promise as new and effective therapies for primary central nervous system lymphoma and other

  19. Gonadal steroid action and brain sex differentiation in the rat.

    PubMed

    Sakuma, Y

    2009-03-01

    Gonadal steroids that establish sexually dimorphic characteristics of brain morphology and physiology act at a particular stage of ontogeny. Testosterone secreted by the testes during late gestational and neonatal periods causes significant brain sexual dimorphism in the rat. This results in both sex-specific behaviour and endocrinology in adults. Sexual differentiation may be due to neurogenesis, migration or survival. Each mechanism appears to be uniquely regulated in a site-specific manner. Thus, the volume of an aggregate of neurones in the rat medial preoptic area (POA), termed the sexually dimorphic nucleus of the POA (SDN-POA), is larger in males than in females. The anteroventral periventricular nucleus (AVPV) is packed with neurones containing oestrogen receptor (ER)beta in female rats but, in males, ERbeta-positive neurones scatter into the more lateral portion of the POA. POA neurones are born up to embryonic days 16-17 and not after parturition. Therefore, neurogenesis is unlikely to contribute to the larger SDN-POA in males. DNA microarray analysis for oestrogen-responsive genes and western blotting demonstrated site-specific regulation of apoptosis- and migration-related genes in the SDN-POA and AVPV.

  20. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    PubMed

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  1. Autoradiographic localization of angiotensin II receptors in rat brain.

    PubMed Central

    Mendelsohn, F A; Quirion, R; Saavedra, J M; Aguilera, G; Catt, K J

    1984-01-01

    The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ( [Sar1]AII) bound with high specificity and affinity (Ka = 2 X 10(9) M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. Images PMID:6324205

  2. Autoradiographic localization of angiotensin II receptors in rat brain

    SciTech Connect

    Mendelsohn, F.A.O.; Quirion, R.; Saavedra, J.M.; Aguilera, G.; Catt, K.J.

    1984-03-01

    The /sup 125/I-labeled agonist analog (1-sarcosine)-angiotensin II ((Sar/sup 1/)AII) bound with high specificity and affinity (K/sub a/ = 2 x 10/sup 9/ M/sup -1/) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. 75 references, 2 figures.

  3. Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure

    NASA Astrophysics Data System (ADS)

    Krasnov, I.

    The structure of brain dorsal raphe nucleus (DRN) was studied in the rats flown in space aboard Space Shuttle "Columbia" (STS-58, SLS-2 program) and dissected on day 13 of the mission ("inflight" rats) and in 5-6 hours after finishing 14-day flight ("postflight" rats). The brain of "inflight" rats were excised after decapitation, sectioned sagitally halves of brain were fixed by immersion in 2,5 % glutaraldehyde in 0.1 M cacodylate buffer pH 7.3 at 4°C and kept in the flight at 4°C. After landing the brain frontal 0.5 mm sections from DRN area were osmificated and embedded in araldite at NASA ARC. The brains of "postflight": and control rats were underwent to the same procedure. Electronmicroscopical analysis, computer morphometry and glial cell count were performed at Moscow. In DRN neuropil of "inflight" rats the most part of axo-dendritic synapses were surrounded by glia cell processes and had decreased electron density of pre- and postsynaptic membrane and pronounced diminution of synaptic vesicle amount while dendrites were characterized by decrease in matrix electron density and microtubule quantity that in total indicates the decline of afferent flow reaching DRN neurons in microgravity. In DRN neurons of "inflight" rats all mitochondria were characterized by evenly increased dimensions, decreased matrix electron density, small amount of short and far- between located cristae and enlarged intermembrane and intercristae spaces, that in total points out low level of coupling of oxidation to phosphorilation, decrease in energy supply of neuron. Amount of ribosome in cytoplasm was significantly decreased indicating lower lever of biosynthetic processes. The last is supported by diminished dimensions of neuronal body, nucleus and nucleolus (place of r RNA synthesis), cross section area of that were reduced in DRN neurons of "inflight" rats by 18.8 % (p < 0.01), 11.1 % and 26.6 % (p <0,005) correspondingly. Ultrastructure and dimensions of intracellular

  4. Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium.

    PubMed

    Feng, Liuxing; He, Xiao; Xiao, Haiqing; Li, Zijie; Li, Fuliang; Liu, Nianqing; Chai, Zhifang; Zhao, Yuliang; Zhang, Zhiyong

    2007-01-01

    Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.

  5. Rat brain pro-oxidant effects of peripherally administered 5 nm ceria 30 days after exposure.

    PubMed

    Hardas, Sarita S; Sultana, Rukhsana; Warrier, Govind; Dan, Mo; Florence, Rebecca L; Wu, Peng; Grulke, Eric A; Tseng, Michael T; Unrine, Jason M; Graham, Uschi M; Yokel, Robert A; Butterfield, D Allan

    2012-10-01

    The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and cerebellum. Glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase levels and activity were measured in addition to levels of inducible nitric oxide (iNOS), and heat shock protein-70 (Hsp70). The blood brain barrier (BBB) was visibly intact and no ceria was seen in the brain cells. Ceria elevated PC and Hsp70 levels in hippocampus and cerebellum, while 3NT and iNOS levels were elevated in the cortex. Whereas glutathione peroxidase and catalase activity were decreased in the hippocampus, GR levels were decreased in the cortex, and GPx and catalase levels were decreased in the cerebellum. The GSH:GSSG ratio, an index of cellular redox status, was decreased in the hippocampus and cerebellum. The results are in accordance with the observation that this nanoscale material remains in this mammal model up to 30 days after its administration and the hypothesis that it exerts pro-oxidant effects on the brain without crossing the BBB. These results have important implications on the potential use of ceria ENM as therapeutic agents.

  6. Detection of cocaine induced rat brain activation by photoacoustic tomography

    PubMed Central

    Jo, Janggun; Yang, Xinmai

    2011-01-01

    Photoacoustic tomography (PAT) was used to detect the progressive changes on the cerebral cortex of Sprague Dawley rats after the administration of cocaine hydrochloride. Different concentrations (0, 2.5, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution were injected into Sprague Dawley rats through tail veins. Cerebral cortex images of the animals were continuously acquired by PAT. For continuous observation, PAT system used multi-transducers to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The obtained photoacoustic images were compared with each other and confirmed that changes in blood volume were induced by cocaine hydrochloride injection. The results demonstrate that PAT may be used to detect the effects of drug abuse-induced brain activation. PMID:21163301

  7. Pathophysiology of microwave radiation: effect on rat brain.

    PubMed

    Kesari, Kavindra Kumar; Kumar, Sanjay; Behari, Jitendra

    2012-01-01

    The study aims to investigate the effect of 2.45 GHz microwave radiation on Wistar rats. Rats of 35 days old with 130 ± 10 g body weight were selected for this study. Animals were divided into two groups: sham exposed and experimental (six animals each). Animals were exposed for 2 h a day for 45 days at 2.45 GHz frequency (power density, 0.21 mW/cm(2)). The whole body specific absorption rate was estimated to be 0.14 W/kg. Exposure took place in a ventilated plexiglas cage and kept in an anechoic chamber under a horn antenna. After completion of the exposure period, rats were killed, and pineal gland and whole brain tissues were isolated for the estimation of melatonin, creatine kinase, caspase 3, and calcium ion concentration. Experiments were performed in a blind manner and repeated. A significant decrease (P < 0.05) was recorded in the level of pineal melatonin of exposed group as compared with sham exposed. A significant increase (P < 0.05) in creatine kinase, caspase 3, and calcium ion concentration was observed in whole brain of exposed group of animals as compared to sham exposed. One-way analysis of variance method was adopted for statistical analysis. The study concludes that a reduction in melatonin or an increase in caspase-3, creatine kinase, and calcium ion may cause significant damage in brain due to chronic exposure of these radiations. These biomarkers clearly indicate possible health implications of such exposures.

  8. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  9. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    PubMed Central

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

  10. 2-hydroxyestradiol modifies serotonergic processes in the male rat brain

    SciTech Connect

    Kowalik, S.

    1985-01-01

    The effects of chronic (5 day) 2-hydroxyestradiol or estradiol on catecholaminergic and serotonergic neurons in the male rat brain were studied. The results indicate estrogen to be specific is inducing changes in dopaminergic systems; whereas its hydroxymetabolite appears to have a preference for serotonergic processes. In particular, in vitro 2-hydroxyestradiol appears to be a potent inhibitor of /sup 3/H-imipramine binding in brain; this inhibition is especially potent in the cortex, where it is equal in potency to serotonin. However, unlike serotonin, which is a competitive inhibitor of imipramine, 2-hydroxyestradiol is an uncompetitive inhibitor of /sup 3/H-imipramine binding in cortex and hypothalamus and a noncompetitive inhibitor in the striatum; this suggests that the inhibition of binding takes place at a point other than the site of serotonin uptake. In vitro 2-hydroxyestradiol also appears to increase the uptake of serotonin into these tissues, a change which would be expected if the imipramine binding is blocked.

  11. Perception of social synchrony induces mother-child gamma coupling in the social brain.

    PubMed

    Levy, Jonathan; Goldstein, Abraham; Feldman, Ruth

    2017-04-11

    The recent call to move from focus on one brain's functioning to two-brain communication initiated a search for mechanisms that enable two humans to coordinate brain response during social interactions. Here, we utilized the mother-child context as a developmentally salient setting to study two-brain coupling. Mothers and their 9-year-old children were videotaped at home in positive and conflictual interactions. Positive interactions were microcoded for social synchrony and conflicts for overall dialogical style. Following, mother and child underwent magnetoencephalography while observing the positive vignettes. Episodes of behavioral synchrony, compared to non-synchrony, increased gamma-band power in the superior temporal sulcus (STS), hub of social cognition, mirroring and mentalizing. This neural pattern was coupled between mother and child. Brain-to-brain coordination was anchored in behavioral synchrony; only during episodes of behavioral synchrony, but not during non-synchronous moments, mother's and child's STS gamma power was coupled. Importantly, neural synchrony was not found during observation of unfamiliar mother-child interaction Maternal empathic/dialogical conflict style predicted mothers' STS activations whereas child withdrawal predicted attenuated STS response in both partners. Results define a novel neural marker for brain-to-brain synchrony, highlight the role of rapid bottom-up oscillatory mechanisms for neural coupling and indicate that behavior-based processes may drive synchrony between two brains during social interactions.

  12. Neuroanatomical distribution of galectin-3 in the adult rat brain.

    PubMed

    Yoo, Hong-Il; Kim, Eu-Gene; Lee, Eun-Jin; Hong, Sung-Young; Yoon, Chi-Sun; Hong, Min-Ju; Park, Sang-Jin; Woo, Ran-Sook; Baik, Tai-Kyoung; Song, Dae-Yong

    2017-04-01

    Galectin-3 is a member of the lectin subfamily that enables the specific binding of β-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

  13. Gene Transfer into Rat Brain Using Adenoviral Vectors

    PubMed Central

    Puntel, Mariana; Kroeger, Kurt M.; Sanderson, Nicholas S.R.; Thomas, Clare E.; Castro, Maria G.; Lowenstein, Pedro R.

    2010-01-01

    Viral vector–mediated gene delivery is an attractive procedure for introducing genes into the brain, both for purposes of basic neuroscience research and to develop gene therapy for neurological diseases. Replication-defective adenoviruses possess many features which make them ideal vectors for this purpose—efficiently transducing terminally differentiated cells such as neurons and glial cells, resulting in high levels of transgene expression in vivo. Also, in the absence of anti-adenovirus immunity, these vectors can sustain very long-term transgene expression within the brain parenchyma. This unit provides protocols for the stereotactic injection of adenoviral vectors into the brain, followed by protocols to detect transgene expression or infiltrates of immune cells by immunocytochemistry or immunofluorescence. ELISPOT and neutralizing antibody assay methodologies are provided to quantitate the levels of cellular and humoral immune responses against adenoviruses. Quantitation of adenoviral vector genomes within the rat brain using qPCR is also described. Curr. Protoc. Neurosci. 50:4.24.1–4.24.49. © 2010 by John Wiley & Sons, Inc. PMID:20066657

  14. 19-Hydroxylation of androgens in the rat brain.

    PubMed Central

    Hahn, E F; Miyairi, S; Fishman, J

    1985-01-01

    Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions. PMID:3857612

  15. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  16. Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19.

    PubMed

    Stein, Lauren M; Yosten, Gina L C; Samson, Willis K

    2016-03-15

    Adropin, a recently described peptide hormone produced in the brain and liver, has been reported to have physiologically relevant actions on glucose homeostasis and lipogenesis, and to exert significant effect on endothelial function. We describe a central nervous system action of adropin to inhibit water drinking and identify a potential adropin receptor, the orphan G protein-coupled receptor, GPR19. Reduction in GPR19 mRNA levels in medial basal hypothalamus of male rats resulted in the loss of the inhibitory effect of adropin on water deprivation-induced thirst. The identification of a novel brain action of adropin and a candidate receptor for the peptide should extend and accelerate the study of the potential therapeutic value of adropin or its mimetics for the treatment of metabolic disorders.

  17. Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain

    PubMed Central

    Shih, Andy Y; Driscoll, Jonathan D; Drew, Patrick J; Nishimura, Nozomi; Schaffer, Chris B; Kleinfeld, David

    2012-01-01

    The cerebral vascular system services the constant demand for energy during neuronal activity in the brain. Attempts to delineate the logic of neurovascular coupling have been greatly aided by the advent of two-photon laser scanning microscopy to image both blood flow and the activity of individual cells below the surface of the brain. Here we provide a technical guide to imaging cerebral blood flow in rodents. We describe in detail the surgical procedures required to generate cranial windows for optical access to the cortex of both rats and mice and the use of two-photon microscopy to accurately measure blood flow in individual cortical vessels concurrent with local cellular activity. We further provide examples on how these techniques can be applied to the study of local blood flow regulation and vascular pathologies such as small-scale stroke. PMID:22293983

  18. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    SciTech Connect

    Yuan, Z.; Du, C.; Yuan, Z.; Luo, Z.; Volkow, N.D.; Pan, Y.; Du, C.

    2010-09-08

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  19. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  20. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  1. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

    PubMed Central

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

  2. NO-Tryptophan: A New Small Molecule Located in the Rat Brain

    PubMed Central

    Mangas, A.; Yajeya, J.; González, N.; Duleu, S.; Geffard, M.; Coveñas, R.

    2016-01-01

    A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. PMID:27734994

  3. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    PubMed Central

    2012-01-01

    Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested. PMID:22709243

  4. New protein extraction/solubilization protocol for gel-based proteomics of rat (female) whole brain and brain regions.

    PubMed

    Hirano, Misato; Rakwal, Randeep; Shibato, Junko; Agrawal, Ganesh Kumar; Jwa, Nam-Soo; Iwahashi, Hitoshi; Masuo, Yoshinori

    2006-08-31

    The rat is an accepted model for studying human psychiatric/neurological disorders. We provide a protocol for total soluble protein extraction using trichloroacetic acid/acetone (TCA/A) from rat (female) whole brain, 10 brain regions and the pituitary gland, and show that two-dimensional gel electrophoresis (2-DGE) using pre-cast immobilized pH (4-7) gradient (IPG) strip gels (13 cm) in the first dimension yields clean silver nitrate stained protein profiles. Though TCA/A precipitation may not be "ideal", the important choice here is the selection of an appropriate lysis buffer (LB) for solubilizing precipitated proteins. Our results reveal enrichment of protein spots by use of individual brain regions rather than whole brain, as well as the presence of differentially expressed spots in their proteomes. Thus individual brain regions provide improved protein coverage and are better suited for differential protein detection. Moreover, using a phosphoprotein-specific dye, in-gel detection of phosphoproteins was demonstrated. Representative high-resolution silver nitrate stained proteome profiles of rat whole brain total soluble protein are presented. Shortcomings apart (failure to separate membrane proteins), gel-based proteomics remains a viable option, and 2-DGE is the method of choice for generating high-resolution proteome maps of rat brain and brain regions.

  5. Anticancer and antioxidant properties of terpinolene in rat brain cells.

    PubMed

    Aydin, Elanur; Türkez, Hasan; Taşdemir, Sener

    2013-09-01

    Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

  6. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  7. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    PubMed Central

    Mann, Phyllis E.

    2014-01-01

    The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated. PMID:24961703

  8. Citrobacter koseri brain abscess in the neonatal rat: survival and replication within human and rat macrophages.

    PubMed

    Townsend, Stacy M; Pollack, Harvey A; Gonzalez-Gomez, Ignacio; Shimada, Hiroyuki; Badger, Julie L

    2003-10-01

    A unique feature of Citrobacter koseri is the extremely high propensity to initiate brain abscesses during neonatal meningitis. Previous clinical reports and studies on infant rats have documented many Citrobacter-filled macrophages within the ventricles and brain abscesses. It has been hypothesized that intracellular survival and replication within macrophages may be a mechanism by which C. koseri subverts the host response and elicits chronic infection, resulting in brain abscess formation. In this study, we showed that C. koseri causes meningitis and brain abscesses in the neonatal rat model, and we utilized histology and magnetic resonance imaging technology to visualize brain abscess formation. Histology and electron microscopy (EM) revealed that macrophages (and not fibroblasts, astrocytes, oligodendrocytes, or neurons) were the primary target for long-term C. koseri infection. To better understand C. koseri pathogenesis, we have characterized the interactions of C. koseri with human macrophages. We found that C. koseri survives and replicates within macrophages in vitro and that uptake of C. koseri increases in the presence of human pooled serum in a dose-dependent manner. EM studies lend support to the hypothesis that C. koseri uses morphologically different methods of uptake to enter macrophages. FcgammaRI blocking experiments show that this receptor primarily facilitates the entry of opsonized C. koseri into macrophages. Further, confocal fluorescence microscopy demonstrates that C. koseri survives phagolysosomal fusion and that more than 90% of intracellular C. koseri organisms are colocalized within phagolysosomes. The ability of C. koseri to survive phagolysosome fusion and replicate within macrophages may contribute to the establishment of chronic central nervous system infection including brain abscesses.

  9. Quantitative Cortical Mapping of Fractional Anisotropy in Developing Rat Brains

    PubMed Central

    Huang, Hao; Yamamoto, Akria; Hossain, Mir Ahamed; Younes, Laurent; Mori, Susumu

    2010-01-01

    Cortical development is associated with a series of events that involve axon and dendrite growth and synaptic formation. Although these developmental processes have been investigated in detail with histology, three-dimensional and quantitative imaging methods for rodent brains may be useful for genetic and pharmacological studies in which cortical developmental abnormalities are suspected. It has been shown that diffusion tensor imaging (DTI) can delineate the columnar organization of the fetal and early neonatal cortex based on a high degree of diffusion anisotropy along the columnar structures. This anisotropy is known to decrease during brain development. In this study, we applied DTI to developing rat brains at five developmental stages, postnatal days 0, 3, 7, 11 and 19, and used diffusion anisotropy as an index to characterize the structural change. Statistical analysis reveals four distinctive cortical areas that demonstrate a characteristic time course of anisotropy loss. This method may provide a means to delineate specific cortical areas and a quantitative method to detect abnormalities in cortical development in rodent pathological models. PMID:18256263

  10. Actin- and myosin-like filaments in rat brain pericytes.

    PubMed

    Le Beux, Y J; Willemot, J

    1978-04-01

    Heavy meromyosin (HMM) labeling was used to identify the nature of the filaments which form bundles in the cytoplasm of the pericytes in brain tissue. Rat brain tissue pieces were incubated in glycerol solutions at 4 degrees and then transferred into buffer (pH 7.0), (1) without HMM, (2) with HMM, (3) with HMM + 5 mM ATP, and (4) with HMM + 2.5 mM Na+ pyrophosphate. In pericytes from untreated tissue, smooth-surfaced microfilaments, averaging 6 nm in diameter, appear to branch and anastomose and to anchor on the plasma membrane. After exposure to HMM, the number and the density of the microfilaments are strikingly increased. These tightly-packed microfilaments are now heavily coated with exogeneous HMM thus increasing in width to 18-20 mm. They intertwine in closely-woven networks. After incubation in HMM solutions containing ATP or Na+ phosphate, they are no longer coated with thick sidearms. It can thus be concluded that these microfilaments are of actin-like nature. In addition, after incubation in ATP, they are intermingled with, and converge onto the surfaces of, thick, tapered filaments, which we have tentatively identified as of myosin-like nature. Thus, it appears that certain of the major elements necessary for contraction are present in brain pericytes.

  11. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Zhang, Ruiying; Wang, Lihong V.

    2015-03-01

    We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  12. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia.

    PubMed

    Lin, Yuqing; Yu, Ping; Hao, Jie; Wang, Yuexiang; Ohsaka, Takeo; Mao, Lanqun

    2014-04-15

    Developing new tools and technologies to enable recording the dynamic changes of multiple neurochemicals is the essence of better understanding of the molecular basis of brain functions. This study demonstrates a microfluidic chip-based online electrochemical system (OECS) for in vivo continuous and simultaneous monitoring of glucose, lactate, and ascorbate in rat brain. To fabricate the microfluidic chip-based detecting system, a microfluidic chip with patterned channel is developed into an electrochemical flow cell by incorporating the chip with three surface-modified indium-tin oxide (ITO) electrodes as working electrodes, a Ag/AgCl wire as reference electrode, and a stainless steel tube as counter electrode. Selective detection of ascorbate is achieved by the use of single-walled carbon nanotubes (SWNTs) to largely facilitate the electrochemical oxidation of ascorbate, while a dehydrogenase-based biosensing mechanism with methylene green (MG) adsorbed onto SWNTs as an electrocatalyst for the oxidation of dihydronicotiamide adenine dinucleotide (NADH) is employed for biosensing of glucose and lactate. To avoid the crosstalk among three sensors, the sensor alignment is carefully designed with the SWNT-modified electrode in the upstream channel and paralleled glucose and lactate biosensors in the downstream channels. With the microfluidic chip-based electrochemical flow cell as the detector, an OECS is successfully established by directly integrating the microfluidic chip-based electrochemical flow cell with in vivo microdialysis. The OECS exhibits a good linear response toward glucose, lactate, and ascorbate with less crosstalk. This property, along with the high stability and selectivity, enables the OECS for continuously monitoring three species in rat brain following brain ischemia.

  13. [Effect of disulfiram on energy metabolism (redox potential shift) coupled to paradoxical sleep episodes in rat cerebral cortex].

    PubMed

    Shvets-Ténéta-Guriĭ, T B; Dubinin, A G; Troshin, G I

    2012-01-01

    Disulfiram (DS) is widely used to treat patients with chronic alcoholism. DS treatment multiplies PS episodes. In this work, DS effect on the number of PS episodes and on the energy metabolism changes in the cerebral cortex (coupled to PS episodes) was investigated for the first time in rats. Polygraphic recording of the redox potential E (with platinum electrodes implanted in several cortical sites), electrocorticogram, neck electromyogram, and general motor activity were made in sleep-wake cycles. Rats received DS (100 mg/kg) with meals for two nights, after which the number of PS episodes increased almost twice during two subsequent sessions (prior to receiving DS). This was evidence of an increase in PS pressure coupled to a decrease of norepinephrine level in the brain. DS also evoked sharp decrease in the amount of the positive E shifts related to PS, which were replaced by the negative E shifts or by the two-phase E shifts (negative-positive waves). The absolute mean amplitude decreased both for the positive E shifts and the negative E shifts. These findings demonstrate prevailing glycolytic compartment as a source of fuel supporting PS and the inhibition in all brain energetic compartments. The data presented well agree with the conception that glycolysis becomes the main source for the brain activity under pathology conditions.

  14. Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

    SciTech Connect

    Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

    1985-02-18

    The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of /sup 125/I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.

  15. Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype.

    PubMed

    Pacelli, Consiglia; Coluccia, Addolorata; Grattagliano, Ignazio; Cocco, Tiziana; Petrosillo, Giuseppe; Paradies, Giuseppe; De Nitto, Emanuele; Massaro, Antonio; Persichella, Michele; Borracci, Pietro; Portincasa, Piero; Carratù, Maria Rosaria

    2010-06-01

    Dietary choline deprivation (CD) is associated with behavioral changes, but mechanisms underlying these detrimental effects are not well characterized. For instance, no literature data are available concerning the CD effects on brain mitochondrial function related to impairment in cognition. Therefore, we investigated brain mitochondrial function and redox status in male Wistar rats fed a CD diet for 28 d. Moreover, the CD behavioral phenotype was characterized. Compared with rats fed a control diet (CTRL), CD rats showed lower NAD-dependent mitochondrial state III and state IV respiration, 40% lower complex I activity, and significantly higher reactive oxygen species production. Total glutathione was oxidatively consumed more in CD than in CTRL rats and the rate of protein oxidation was 40% higher in CD than in CTRL rats, reflecting an oxidative stress condition. The mitochondrial concentrations of cardiolipin, a phospholipid required for optimal activity of complex I, was 20% lower in CD rats than in CTRL rats. Compared with CTRL rats, the behavioral phenotype of CD rats was characterized by impairment in motor coordination and motor learning assessed with the rotarod/accelerod test. Furthermore, compared with CTRL rats, CD rats were less capable of learning the active avoidance task and the number of attempts they made to avoid foot shock was fewer. The results suggest that CD-induced dysfunction in brain mitochondria may be responsible for impairment in cognition and underline that, similar to the liver, the brain also needs an adequate choline supply for its normal functioning.

  16. Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics.

    PubMed

    Becker, J Sabine; Matusch, Andreas; Palm, Christoph; Salber, Dagmar; Morton, Kathryn A; Becker, J Susanne

    2010-02-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.

  17. Involvement of a proton-coupled organic cation antiporter in the blood-brain barrier transport of amantadine.

    PubMed

    Suzuki, Toyofumi; Aoyama, Takahiko; Suzuki, Naoto; Kobayashi, Masaru; Fukami, Toshiro; Matsumoto, Yoshiaki; Tomono, Kazuo

    2016-09-01

    The blood-to-brain transport of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, has been shown previously to participate in the cationic drug-sensitive transport system across the mouse blood-brain barrier (BBB). The purpose of the present study was to characterize the influx transport system by means of both an in situ mouse brain perfusion technique and in vitro studies using rat immortalized brain capillary endothelial cells (GPNT). The observed concentration-dependent initial uptake rate of [(3) H]amantadine suggested the involvement of a carrier-mediated transport mechanism. The normal uptake at physiological pH 7.4 was decreased by 72.9% in acidic perfusate, while it was increased by 35.3% in alkaline perfusate. These results suggest that pH-dependent transport is regulated by utilizing an oppositely directed proton gradient as a driving force. In addition, the [(3) H]amantadine uptake was moderately inhibited by the adamantane structural analogs (rimantadine and memantine) and other cationic drugs (pyrilamine, clonidine, nicotine, etc.), but not by substrates or inhibitors of the well-characterized organic cation transporters (tetraethylammonium, l-carnitine and choline). A similar inhibition pattern was observed between the in vivo studies and the in vitro experiments. These results indicate that the influx transport for amantadine across the BBB involves a proton-coupled organic cation antiporter. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Delayed cytokine expression in rat brain following experimental contusion.

    PubMed

    Holmin, S; Schalling, M; Höjeberg, B; Nordqvist, A C; Skeftruna, A K; Mathiesen, T

    1997-03-01

    Proinflammatory cytokines mediate brain injury in experimental studies. This study was undertaken to analyze the production of proinflammatory cytokines in experimental contusion. A brain contusion causing delayed edema was mimicked experimentally in rats using a weight-drop model. Intracerebral expression of the cytokines interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF alpha), IL-6, and interferon-gamma (IFN gamma) was studied by in situ hybridization and immunohistochemistry. The animals were killed at 6 hours or 1, 2, 4, 6, 8, or 16 days postinjury. In the injured area, no messenger (m)RNA expression was seen during the first 2 days after the trauma. On Days 4 to 6 posttrauma, however, strong IL-1 beta, TNF alpha, and IL-6 mRNA expression was detected in mononuclear cells surrounding the contusion. Expression of IFN gamma was not detected. Immunohistochemical double labeling confirmed the in situ hybridization results and demonstrated that mononuclear phagocytes and astrocytes produced IL-1 beta and that mainly astrocytes produced TNF alpha. The findings showed, somewhat unexpectedly, a late peak of intracerebral cytokine production in the injured area and in the contralateral corpus callosum, allowing for both local and global effects on the brain. An unexpected difference in the cellular sources of TNF alpha and IL-1 beta was detected. The cytokine pattern differs from that seen in other central nervous system inflammatory diseases and trauma models, suggesting that the intracerebral immune response is not a uniform event. The dominance of late cytokine production indicates that many cytokine effects are late events in an experimental contusion: Different pathogenic mechanisms may thus be operative at different times after brain injury.

  19. Couples' happiness and its relationship to functioning in everyday life after brain injury.

    PubMed

    Eriksson, Gunilla; Tham, Kerstin; Fugl-Meyer, Axel R

    2005-03-01

    The objective of this survey was to identify couples' joint perception of their satisfaction with life as a whole when one of the persons in the couple had acquired brain injury between one and five years earlier. The focus was on the influence that functioning and disability in everyday life have on the couple's joint life satisfaction after brain injury. The sample consisted of 55 couples, and the mean age of the brain-injured persons was 51 years. Both persons in the couple answered a mailed questionnaire encompassing questions concerning perceived impairments, activity limitations, participation restrictions, and life satisfaction. The results showed that in 16 of the 55 couples both partners were satisfied with life as a whole. The joint experience of life satisfaction was significantly related to the couple's functioning in everyday life, and specifically to perceived participation in leisure time and in their social life, and in their ability to wash clothes. Important implications from this study, showing that only one-third of the couples were satisfied, are that the partners should be included to a greater extent in the rehabilitation process and the couple's perspective of what they find difficult to deal with should serve as a guide during rehabilitation.

  20. MALDI imaging and in situ identification of integral membrane proteins from rat brain tissue sections

    PubMed Central

    Nicklay, Joshua J.; Harris, Glenn A.; Schey, Kevin L.; Caprioli, Richard M.

    2013-01-01

    Transmembrane proteins are greatly underrepresented in data generated by imaging mass spectrometry (IMS) because of analytical challenges related to their size and solubility. Here we present the first example of MALDI IMS of two highly modified multi-transmembrane domain proteins, myelin proteolipid protein (PLP, 30 kDa) and DM-20 (26 kDa), from various regions of rat brain, namely the cerebrum, cerebellum, and medulla. We utilize a novel tissue pre-treatment aimed at transmembrane protein enrichment to show the in situ distribution of fatty acylation of these proteins, particularly of post-translational palmitoylation. Additionally, we demonstrate the utility of protease-encapsulated hydrogels for spatially localized on-tissue protein digestion and peptide extraction for subsequent direct coupling to LC-MS/MS for protein identification. PMID:23829295

  1. Localization and labeling of rat brain in MR image based on Paxinos-Watson atlas

    NASA Astrophysics Data System (ADS)

    Cao, Jie; Cai, Chao; Ding, Mingyue; Zhou, Chengping

    2006-03-01

    Localization and labeling of function regions in brain is an important topic in experimental brain sciences because the huge amount of data collected by neuroscientists will become meaningless if we cannot give them a precise description of their locations. In this paper, we proposed a localization and labelling method of 3D MR image of rat brain based on Paxinos-Watson atlas. Our objective is to use the specific atlas to accomplish localization and labeling of specified tissue of interest (TOI) to mimic a veteran expert such that invisible or unclear anatomic function regions in the MR images of rat brain can be automatically identified and marked. We proposed a multi-step method to locate and label the TOIs from the MR image of rat brain. Firstly, pre-processing. It aims at the digitization and 3D reconstruction of the atlas and MRI of rat brain. Secondly, two-step registration. The global registration is to eliminate the big misalign and section angle offset as well as the scale between the MRI and atlas. We can choose some unambiguous and characteristic points manually, and based on these correspondences a coarse registration is obtained using affine model. The local registration is to address individual variability of rat brain that can be performed by using Snake model. Thirdly, post-processing. The goal is to locate and label the TOIs in the selected MR image of rat brain slice guided by well-registered atlas. The experiments demonstrated the feasibility of our method.

  2. Kinetic characteristics of nitric oxide synthase from rat brain.

    PubMed Central

    Knowles, R G; Palacios, M; Palmer, R M; Moncada, S

    1990-01-01

    The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax. of 42 pmol of NO formed.min-1.mg of protein-1 and a Km for L-arginine of 8.4 microM. Three analogues of L-arginine, namely NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-iminoethyl-L-ornithine inhibited the brain NO synthase. All three compounds were competitive inhibitors of the enzyme with Ki values of 0.7, 0.4 and 1.2 microM respectively. PMID:1695842

  3. Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

    PubMed Central

    Innis, R B; Corrêa, F M; Uhl, G R; Schneider, B; Snyder, S H

    1979-01-01

    Cholecystokinin octapeptide-like (CCK-OP-like) immunoreactivity was localized in the rat brain by using the indirect immunofluorescence method. Specificity in immunohistochemical studies was demonstrated by the virtual elimination of staining with either preimmune sera or sera preadsorbed with CCK-OP and by the achievement of similar fluorescent patterns with two different primary anti-CCK-OP sera. CCK-OP-like fluorescence was localized in neuronal cell bodies, fibers, and varicose terminals. The most dense collections of CCK-OP cells occurred in the periaqueductal gray and in the dorsomedial hypothalamus. Substantial numbers of cells and fibers also were present in the medial/dorsal and perirhinal cortex; more limited groups of cells were found in the pyramidal layer of the hippocampus and in the dorsal raphe. Images PMID:284371

  4. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    NASA Astrophysics Data System (ADS)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  5. Antioxidant effects of calcium antagonists in rat brain homogenates.

    PubMed

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T

    2000-06-01

    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  6. Expression of connexin36 in the adult and developing rat brain.

    PubMed

    Belluardo, N; Mudò, G; Trovato-Salinaro, A; Le Gurun, S; Charollais, A; Serre-Beinier, V; Amato, G; Haefliger, J A; Meda, P; Condorelli, D F

    2000-05-19

    The distribution of connexin36 (Cx36) in the adult rat brain and retina has been analysed at the protein (immunofluorescence) and mRNA (in situ hybridization) level. Cx36 immunoreactivity, consisting primarily of round or elongated puncta, is highly enriched in specific brain regions (inferior olive and the olfactory bulb), in the retina, in the anterior pituitary and in the pineal gland, in agreement with the high levels of Cx36 mRNA in the same regions. A lower density of immunoreactive puncta can be observed in several brain regions, where only scattered subpopulations of cells express Cx36 mRNA. By combining in situ hybridization for Cx36 mRNA with immunohistochemistry for a general neuronal marker (NeuN), we found that neuronal cells are responsible for the expression of Cx36 mRNA in inferior olive, cerebellum, striatum, hippocampus and cerebral cortex. Cx36 mRNA was also demonstrated in parvalbumin-containing GABAergic interneurons of cerebral cortex, striatum, hippocampus and cerebellar cortex. Analysis of developing brain further revealed that Cx36 reaches a peak of expression in the first two weeks of postnatal life, and decreases sharply during the third week. Moreover, in these early stages of postnatal development Cx36 is detectable in neuronal populations that are devoid of Cx36 mRNA at the adult stage. The developmental changes of Cx36 expression suggest a participation of this connexin in the extensive interneuronal coupling which takes place in several regions of the early postnatal brain.

  7. Purification of the high-Km aldehyde reductase from rat brain and liver and from ox brain.

    PubMed Central

    Rivett, A J; Smith, I L; Tipton, K F

    1981-01-01

    A procedure is described that yields an apparently homogeneous preparation of the high-Km aldehyde reductase from rat brain. This procedure is also applicable to the purification of this enzyme from rat liver and ox brain. In the latter case, however, the purified preparation could be resolved into two protein bands, both of which had enzyme activity, by polyacrylamide-gel electrophoresis. Since a sample of the ox brain enzyme from an earlier step in the purification procedure only showed the presence of a single band of activity after electrophoresis, this apparent multiplicity probably results from modification of the enzyme, possibly by oxidation, during the final step of the purification. A number of properties of the rat brain enzyme were determined and these were compared with those of the enzyme from rat liver. The two preparations were similar in their stabilities, behaviour during purification, kinetic properties, electrophoretic mobilities and amino acid compositions. Antibodies to the rat liver enzyme cross-reacted with that from brain and the inhibition of both these preparations by the antiserum was similar, further supporting the view that the enzymes from these two sources were closely similar if not identical. PMID:6798966

  8. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  9. Immunocytochemical localization of the GABA transporter in rat brain.

    PubMed

    Radian, R; Ottersen, O P; Storm-Mathisen, J; Castel, M; Kanner, B I

    1990-04-01

    Polyclonal antibodies were raised against the GABA transporter (GABA-Tp) purified from rat brain tissue (Radian et al., 1986) and used for immunocytochemical localization of the antigen in several rat brain areas, including the cerebellum, hippocampus, substantia nigra, and cerebral cortex. Light microscopic studies with the peroxidase-antiperoxidase and biotin-avidin-peroxidase techniques suggested that GABA-Tp is localized in the same types of axons and terminals that contain endogenous GABA, as judged by comparison with parallel sections incubated with antibodies against glutaraldehyde-conjugated GABA. However, as expected from biochemical results, different neurons differed in their relative contents of GABA-Tp and GABA; thus, GABA-Tp was relatively low in striatonigral and Purkinje axon terminals and relatively high in nerve plexus around the bases of cerebellar Purkinje cells and hippocampal pyramidal and granule cells. The GABA-Tp antiserum did not produce detectable labeling of nerve cell bodies. Electron microscopic studies supported the light microscopic observations and provided direct evidence of cellular co-localization of GABA-Tp and GABA (as visualized by the peroxidase-antiperoxidase technique and postembedding immunogold labeling, respectively). The ultrastructural studies indicated the presence of GABA-Tp also in glial processes but not in glial cell bodies. The relative intensity of the neuronal and glial staining varied among regions: glial staining predominated over neuronal staining in the substantia nigra, whereas the converse was true in the cerebellum and hippocampus. The present immunocytochemical data demonstrate directly what has previously been inferred from biochemical and autoradiographic evidence: that the mechanisms for high-affinity GABA uptake is selectively and differentially localized in GABAergic neurons and in glial cells.

  10. Sleep deprivation has a neuroprotective role in a traumatic brain injury of the rat.

    PubMed

    Martinez-Vargas, Marina; Estrada Rojo, Francisco; Tabla-Ramon, Erika; Navarro-Argüelles, Hilda; Ortiz-Lailzon, Nathan; Hernández-Chávez, Alejandro; Solis, Barbara; Martínez Tapia, Ricardo; Perez Arredondo, Adan; Morales-Gomez, Julio; Gonzalez-Rivera, Ruben; Nava-Talavera, Karen; Navarro, Luz

    2012-11-07

    During the process of a brain injury, responses to produce damage and cell death are activated, but self-protective responses that attempt to maintain the integrity and functionality of the brain are also activated. We have previously reported that the recovery from a traumatic brain injury (TBI) is better in rats if it occurs during the dark phase of the diurnal cycle when rats are in the waking period. This suggests that wakefulness causes a neuroprotective role in this type of injury. Here we report that 24h of total sleep deprivation after a TBI reduces the morphological damage and enhances the recovery of the rats, as seen on a neurobiological scale.

  11. Effects of beta-hydroxybutyrate on brain vascular permeability in rats with traumatic brain injury.

    PubMed

    Orhan, Nurcan; Ugur Yilmaz, Canan; Ekizoglu, Oguzhan; Ahishali, Bulent; Kucuk, Mutlu; Arican, Nadir; Elmas, Imdat; Gürses, Candan; Kaya, Mehmet

    2016-01-15

    This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-κB) were performed, and Glut-1 and NF-κB activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-κB protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-κB expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals.

  12. Expression of GABA receptor rho subunits in rat brain.

    PubMed

    Boue-Grabot, E; Roudbaraki, M; Bascles, L; Tramu, G; Bloch, B; Garret, M

    1998-03-01

    The GABA receptor rho1, rho2, and rho3 subunits are expressed in the retina where they form bicuculline-insensitive GABA(C) receptors. We used northern blot, in situ hybridization, and RT-PCR analysis to study the expression of rho subunits in rat brains. In situ hybridization allowed us to detect rho-subunit expression in the superficial gray layer of the superior colliculus and in the cerebellar Purkinje cells. RT-PCR experiments indicated that (a) in retina and in domains that may contain functional GABA(C) receptors, rho2 and rho1 subunits are expressed at similar levels; and (b) in domains and in tissues that are unlikely to contain GABA(C) receptors, rho2 mRNA is enriched relative to rho1 mRNA. These results suggest that both rho1 and rho2 subunits are necessary to form a functional GABA(C) receptor. The use of RT-PCR also showed that, except in the superior colliculus, rho3 is expressed along with rho1 and rho2 subunits. We also raised an antibody against a peptide sequence unique to the rho1 subunit. The use of this antibody on cerebellum revealed the rat rho1 subunit in the soma and dendrites of Purkinje neurons. The allocation of GABA(C) receptor subunits to identified neurons paves the way for future electrophysiological studies.

  13. The effects of chronic imidazoline drug treatment on glial fibrillary acidic protein concentrations in rat brain.

    PubMed Central

    Olmos, G.; Alemany, R.; Escriba, P. V.; García-Sevilla, J. A.

    1994-01-01

    1. The concentration of the astrocytic marker, glial fibrillary acidic protein (GFAP) was quantitated by immunoblotting (western blotting) in the rat brain after treatment with various imidazoline drugs and other agents. 2. Chronic (7 days) but not acute (1 day) treatment with the imidazoline drugs, cirazoline (1 mg kg-1, i.p.) and idazoxan (10 mg kg-1, i.p.), but not with the structurally related alpha 2-adrenoceptor antagonists, RX821002 (2-methoxy idazoxan) (10 mg kg-1, i.p.) and efaroxan (10 mg kg-1, i.p.), markedly increased (45%) GFAP immunoreactivity in the rat cerebral cortex. Chronic treatment (7 days) with yohimbine (10 mg kg-1, i.p.), a non-imidazoline alpha 2-adrenoceptor antagonist, did not significantly modify GFAP immunoreactivity in the cerebral cortex. 3. Chronic treatment (7 days) with cirazoline and idazoxan did not alter the density of brain monoamine oxidase (MAO)-B sites labelled by [3H]-Ro 19-6327 (lazabemide), another relevant astroglial marker. Moreover, these imidazoline drug treatments did not modify the levels of alpha-tubulin in the cerebral cortex. These negative results reinforced the specificity of the effects of imidazoline drugs on GFAP. 4. Irreversible inactivation of brain alpha 2-adrenoceptors (and other neurotransmitters receptors) after treatment with an optimal dose of the peptide-coupling agent EEDQ (1.6 mg kg-1, i.p., for 6-24 h) did not alter GFAP immunoreactivity in the cerebral cortex. These results further disproved the involvement of these receptors on astroglial cells in the tonic control of GFAP levels.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4 PMID:8032628

  14. Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures.

    PubMed

    Kristensen, B W; Noraberg, J; Thiébaud, P; Koudelka-Hep, M; Zimmer, J

    2001-03-30

    In this study we examined the passive biocompatibility of a three-dimensional microelectrode array (MEA), designed to be coupled to organotypic brain slice cultures for multisite recording of electrophysiological signals. Hippocampal (and corticostriatal) brain slices from 1-week-old (and newborn) rats were grown for 4-8 weeks on the perforated silicon chips with silicon nitride surfaces and 40 microm sized holes and compared with corresponding tissue slices grown on conventional semiporous membranes. In terms of preservation of the basic cellular and connective organization, as visualized by Nissl staining, Timm sulphide silver-staining, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) immunostaining, the slice cultures grown on chips did not differ from conventionally grown slice cultures. Neither were there any signs of astrogliosis or neurodegeneration around the upper recording part of the 47-microm-high platinum-tip electrodes. Slice cultures grown on a separate set of chips with platinum instead of silicon nitride surfaces also displayed normal MAP2 and GFAP immunostaining. The width of the GFAP-rich zone (glia limitans) at the bottom surface of the slice cultures was the same ( approximately 20 microm) in cultures grown on chips with silicon nitride and platinum surfaces and on conventional insert membranes. The slice cultures grown on chips maintained a normal, subfield differentiated susceptibility to the glutamate receptor agonist N-methyl-D-aspartate (NMDA) and the neurotoxin trimethyltin (TMT), as demonstrated by the cellular uptake of propidium iodide (PI), which was used as a reproducible and quantifiable marker for neuronal degeneration. We conclude that organotypic brain slice cultures can grow on silicon-based three-dimensional microelectrode arrays and develop normally with display of normal subfield differentiated susceptibilities to known excito- and neurotoxins. From this it is anticipated that the set

  15. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

    PubMed Central

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-01-01

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID:27374823

  16. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

    PubMed

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-06-30

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

  17. [Lipids from gray and white rat brain matter in autolysis].

    PubMed

    Gribanov, G A; Il'iashenko, D V

    1993-01-01

    A decrease in relative content of phospholipids and cholesterol simultaneously with increase in cholesterol esters and free fatty acids were detected in tissues of rat brain gray and white matters during autolysis at 37 degrees within 6-7 min, 1, 4 and 24 hrs; the most distinct alterations were observed in lipids of the gray matter especially at early (6-7 min) and late (24 hrs) stages of autolysis. In the gray matter, relative content of all the lipid fractions studied was restored to initial level within 4 hrs of incubation. In the white matter, during autolysis the content of cholesterol varied, the content of phospholipids was only slightly increased, while the level of free fatty acids was increased only at 24 hrs of incubation with synchronous decrease in content of triacylglycerols, cholesterol and, partially, phospholipids. These experimental data are of importance in resuscitation. Both common and dissimilar mechanisms of these lipid alterations are discussed. Not only the complex of hydrolase reactions but also that of transacylase and other reactions, involved in the degradation and biotransformation of brain lipids in autolysis, were noted.

  18. Are soluble and membrane-bound rat brain acetylcholinesterase different

    SciTech Connect

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. )

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  19. The turnover of protein in discrete areas of rat brain

    PubMed Central

    Austin, Lawrence; Lowry, Oliver H.; Brown, Joseph G.; Carter, Joyce G.

    1972-01-01

    1. Rats were injected serially with [14C]glucose to obtain a constant specific radioactivity of brain amino acids. Measurements with this system for periods of up to 8h gave an apparent mean half-life for protein in whole brain of 85h (indicating the presence of a protein fraction with much more rapid turnover than this). 2. The half-lives of proteins in the granule-cell, molecular and white-matter layers of cerebellum were also determined. These had values of 33, 59 and 136h respectively. In addition, the incorporation into protein in six layers of the cerebral cortex, subjacent white matter and five layers of Ammon's horn was studied. All cell-body layers incorporated amino acids at about the same rate irrespective of location, and these rates were considerably higher than those for incorporation into proteins in areas rich in dendrites or fibre tracts. 3. A new method for measuring small amounts of glutamate with a cyclic enzyme system is presented. PMID:4341911

  20. Brain Metabolic Changes in Rats following Acoustic Trauma.

    PubMed

    He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

    2017-01-01

    Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive "tinnitus-causing" network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine

  1. Brain Metabolic Changes in Rats following Acoustic Trauma

    PubMed Central

    He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

    2017-01-01

    Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine

  2. Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

    PubMed

    Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

    2009-01-01

    The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

  3. Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain.

    PubMed

    Spain, Aisling; Howarth, Clare; Khrapitchev, Alexandre A; Sharp, Trevor; Sibson, Nicola R; Martin, Chris

    2015-12-01

    The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N=6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data.

  4. Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

    PubMed Central

    Spain, Aisling; Howarth, Clare; Khrapitchev, Alexandre A.; Sharp, Trevor; Sibson, Nicola R.; Martin, Chris

    2015-01-01

    The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N = 6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data. PMID:26192543

  5. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    PubMed

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  6. Yawning and Stretching Predict Brain Temperature Changes in Rats: Support for the Thermoregulatory Hypothesis

    PubMed Central

    Shoup-Knox, Melanie L.; Gallup, Andrew C.; Gallup, Gordon G.; McNay, Ewan C.

    2010-01-01

    Recent research suggests that yawning is an adaptive behavior that functions to promote brain thermoregulation among homeotherms. To explore the relationship between brain temperature and yawning we implanted thermocoupled probes in the frontal cortex of rats to measure brain temperature before, during and after yawning. Temperature recordings indicate that yawns and stretches occurred during increases in brain temperature, with brain temperatures being restored to baseline following the execution of each of these behaviors. The circulatory changes that accompany yawning and stretching may explain some of the thermal similarities surrounding these events. These results suggest that yawning and stretching may serve to maintain brain thermal homeostasis. PMID:21031034

  7. Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats.

    PubMed

    Mori, M; Wilber, J F; Nakamoto, T

    1984-12-17

    We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.

  8. [The effect of various amines on TRH contents in rat brain (author's transl)].

    PubMed

    Mitsuma, T; Hirooka, Y; Nihei, N

    1976-08-20

    To study the effect of vatious amines on TRH contents in rat brain, various amines or inhibitor of synthesis of amines were injected into rat through i.v. or i.p.. Rats were decapitated and brain was frozen in dry ice and aceton. TRH contents in hypothalamus(H), cerebrum(C) and cerebellum and brain stem (C and S) were measured by TRH radioimmunoassay. TRH contents in normal rats were 3.9+/-0.5ng in H, 2.6+/-0.5NG IN C and 1.6+/-0.3ng in C and S. TRH contents in all parts of brain were increased in L-DOPA treated group and did not change in T3 or T4 treated group. TRH contents in all parts of brain were decreased in alpha-methyl-DOPA, alpha-methyl-para-tyrosine, fusaric acid and 5-HTP treated groups. In D,L-p-chlorophenylalanine treated group TRH contents in brain were increased only in hypothalamus. In L-DOPA or 5-HTP treated group with T4 or T3 preadministration, TRH contents in all parts of brain were same levels of L-DOPA or 5-HTP treated group. The above data suggested the TRH contents in rat brain were increased with increase of dopamine level in rat brain and decreased with increase of serotonine level or decrease of noradrenaline level in rat brain and inhibitory effect of T4 or T3 on TRH release might be mediated through dopaminergic and serotonergic mechanism.

  9. Cross-frequency coupling of brain oscillations in studying motivation and emotion.

    PubMed

    Schutter, Dennis J L G; Knyazev, Gennady G

    2012-03-01

    Research has shown that brain functions are realized by simultaneous oscillations in various frequency bands. In addition to examining oscillations in pre-specified bands, interactions and relations between the different frequency bandwidths is another important aspect that needs to be considered in unraveling the workings of the human brain and its functions. In this review we provide evidence that studying interdependencies between brain oscillations may be a valuable approach to study the electrophysiological processes associated with motivation and emotional states. Studies will be presented showing that amplitude-amplitude coupling between delta-alpha and delta-beta oscillations varies as a function of state anxiety and approach-avoidance-related motivation, and that changes in the association between delta-beta oscillations can be observed following successful psychotherapy. Together these studies suggest that cross-frequency coupling of brain oscillations may contribute to expanding our understanding of the neural processes underlying motivation and emotion.

  10. Changing numbers of neuronal and non-neuronal cells underlie postnatal brain growth in the rat

    PubMed Central

    Bandeira, Fabiana; Lent, Roberto; Herculano-Houzel, Suzana

    2009-01-01

    The rat brain increases >6× in mass from birth to adulthood, presumably through the addition of glial cells and increasing neuronal size, without the addition of neurons. To test this hypothesis, here we investigate quantitatively the postnatal changes in the total number of neuronal and non-neuronal cells in the developing rat brain, and examine how these changes correlate with brain growth. Total numbers of cells were determined with the isotropic fractionator in the brains of 53 Wistar rats, from birth to young adulthood. We find that at birth, >90% of the cells in the rat brain are neurons. Following a dormant period of ≈3 days after birth, the net number of neurons in the cerebral cortex, hippocampus, and remaining tissue (excluding cerebellum and olfactory bulb) doubles during the first week, then is reduced by 70% during the second postnatal week, concurrently with net gliogenesis. A second round of net addition of 6 million neurons is observed in the cerebral cortex over the following 2 weeks. During the first postnatal week, brain growth relates mainly to increased numbers of neurons of larger average size. In the second and third weeks, it correlates with increased numbers of non-neuronal cells that are smaller in size than the preexisting neurons. Postnatal rat brain development is thus characterized by dramatic changes in the cellular composition of the brain, whose growth is governed by different combinations of cell addition and loss, and changes in average cell size during the first months after birth. PMID:19666520

  11. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats.

    PubMed

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  12. Complex modulation of the expression of PKC isoforms in the rat brain during chronic type 1 diabetes mellitus.

    PubMed

    Vetri, Francesco; Chavez, Rafael; Xu, Hao-Liang; Paisansathan, Chanannait; Pelligrino, Dale A

    2013-01-15

    We previously demonstrated that chronic hyperglycemia has a detrimental influence on neurovascular coupling in the brain-an effect linked to an alteration in the protein kinase C (PKC)-mediated phosphorylation pattern. Moreover, the activity of PKC was increased, in diabetic rat brain, in a tissue fraction composed primarily of the superficial glia limitans and pial vessels, but trended toward a decrease in cerebral cortical gray matter. However, that study did not examine the expression patterns of PKC isoforms in the rat brain. Thus, in a rat model of streptozotocin (STZ)-induced chronic type 1 diabetes mellitus (T1DM), and in non-diabetic (ND) controls, two hypotheses were addressed. First, chronic T1DM is accompanied by changes in the expression of PKC-α, βII, γ, δ, and ε Second, those changes differ when comparing cerebral cortex and glio-pial tissue. In addition, we analyzed the expression of a form of PKC-γ, phosphorylated on threonine 514 (pT514-PKC-γ), as well as the receptor for activated C kinase 1 (RACK1). The expression pattern of different PKC isoforms was altered in a complex and tissue-specific manner during chronic hyperglycemia. Notably, in the gray matter, PKC-α expression significantly decreased, while pT514-PKC-γ expression increased. However, PKC-βII, -γ, -δ, -ε, and RACK1 expressions did not change. Conversely, in glio-pial tissue, PKC-α and RACK1 were upregulated, whereas PKC-γ, pT514-PKC-γ, and PKC-ε were downregulated. PKC-βII, and PKC-δ, were unchanged. These findings suggest that the PKC activity increase previously seen in the glio-pial tissue of diabetic rats may be due to the selective upregulation of PKC-α, and ultimately lead to the impairment of neurovascular coupling.

  13. Cloning and expression of an A1 adenosine receptor from rat brain

    SciTech Connect

    Mahan, L.C.; McVittie, L.D.; Smyk-Randall, E.M.; Nakata, H.; Monsma, F.J. Jr.; Gerfen, C.R.; Sibley, D.R. )

    1991-07-01

    The authors have used the polymerase chain reaction technique to selectively amplify guanine nucleotide-binding regulatory protein (G protein)-coupled receptor cDNA sequences from rat striatal mRNA, using sets of highly degenerate primers derived from transmembrane sequences of previously cloned G protein-coupled receptors. A novel cDNA fragment was identified, which exhibits considerable homology to various members of the G protein-coupled receptor family. This fragment was used to isolate a full-length cDNA from a rat striatal library. A 2.2-kilobase clone was obtained that encodes a protein of 326 amino acids with seven transmembrane domains, as predicted by hydropathy analysis. Stably transfected mouse A9-L cells and Chinese hamster ovary cells that expressed mRNA for this clone were screened with putative receptor ligands. Saturable and specific binding sites for the A1 adenosine antagonist (3H)-1,3-dipropyl-8-cyclopentylxanthine were identified on membranes from transfected cells. The rank order of potency and affinities of various adenosine agonist and antagonist ligands confirmed the identity of this cDNA clone as an A1 adenosine receptor. The high affinity binding of A1 adenosine agonists was shown to be sensitive to the nonhydrolyzable GTP analog guanylyl-5{prime}-imidodiphosphate. In adenylyl cyclase assays, adenosine agonists inhibited forskolin-stimulated cAMP production by greater than 50%, in a pharmacologically specific fashion. Northern blot and in situ hybridization analyses of receptor mRNA in brain tissues revealed two transcripts of 5.6 and 3.1 kilobases, both of which were abundant in cortex, cerebellum, hippocampus, and thalamus, with lower levels in olfactory bulb, striatum, mesencephalon, and retina. These regional distribution data are in good agreement with previous receptor autoradiographic studies involving the A1 adenosine receptor.

  14. Rate of utilization of glucose and `compartmentation' of α-oxoglutarate and glutamate in rat brain

    PubMed Central

    Gaitonde, M. K.

    1965-01-01

    1. The rate of incorporation of 14C into pyruvate, α-oxoglutarate, lactate and glucose of rat tissues was measured after the subcutaneous injection of uniformly labelled glucose. 2. In rat brain the specific radioactivities of lactate and glucose were similar to that of alanine. In liver the specific radioactivity of glucose was considerably higher than that of lactate or alanine. 3. The specific radioactivities of α-oxo acids of rat brain were lower than those of corresponding amino acids, alanine and glutamate. These findings have been explained in relation to metabolic compartments in vivo. 4. The approximate estimated rate of glucose utilization in rat brain in vivo is 0·96μmole/g. of brain/min. PMID:14342519

  15. Neonatal hypothyroidism affects the adenine nucleotides metabolism in astrocyte cultures from rat brain.

    PubMed

    Braganhol, Elizandra; Bruno, Alessandra Nejar; Bavaresco, Luci; Barreto-Chaves, Maria Luiza M; Sarkis, João José Freitas; Battastini, Ana Maria Oliveira

    2006-04-01

    Neonatal hypothyroidism is associated with multiple and severe brain alterations. We recently demonstrated a significant increase in hydrolysis of AMP to adenosine in brain of hypothyroid rats at different ages. However, the origin of this effect was unclear. Considering the effects of adenine nucleotides to brain functions and the harmful effects of neonatal hypothyroidism to normal development of the central nervous system, in this study we investigated the metabolism of adenine nucleotides in hippocampal, cortical and cerebellar astrocyte cultures from rats submitted to neonatal hypothyroidism. ATP and AMP hydrolysis were enhanced by 52 and 210%, respectively, in cerebellar astrocytes from hypothyroid rats. In hippocampus of hypothyroid rats, the 47% increase in AMP hydrolysis was significantly reverted when the astrocytes were treated with T3. Therefore, the imbalance in the ATP and adenosine levels in astrocytes, during brain development, may contribute to some of the effects described in neonatal hypothyroidism.

  16. Expression of aquaporin-4 and pathological characteristics of brain injury in a rat model of traumatic brain injury

    PubMed Central

    ZHANG, CHENGCHENG; CHEN, JIANQIANG; LU, HONG

    2015-01-01

    Aquaporin 4 (AQP4) is a widely distributed membrane protein, which is found in glial cells, ependymocytes and capillary endothelial cells in the brain, and particularly in the choroid plexus. AQP4 is a key regulator of water metabolism, and changes in its expression following brain injury are associated with pathological changes in the damaged side of the brain; however, the effects of brain injury on AQP4 and injury-induced pathological changes in the contralateral non-damaged side of the brain remain to be fully elucidated. In the present study, male Sprague-Dawley rats were subjected to traumatic brain injury (TBI) and changes in brain water content, the expression of AQP4 expression and pathological characteristics in the damaged and contralateral non-damaged sides of the brain were examined. In the damaged side of the brain, vasogenic edema appeared first, followed by cellular edema. The aggravated cellular edema in the damaged side of the brain resulted in two periods of peak edema severity. Pathological changes in the contralateral non-damaged side of the brain occurred later than those in the damaged side; cellular edema appeared first, followed by vasogenic edema, which was alleviated earlier than the cellular edema. AQP4 was downregulated during vasogenic edema, and upregulated during cellular edema. Taken together, these results suggested that the downregulation of AQP4 was a result of vasogenic edema and that the upregulation of AQP4 may have induced cellular edema. PMID:26459070

  17. Concentration and persistence of tin in rat brain and blood following dibutyltin exposure during development.

    PubMed

    Moser, V C; McGee, J K; Ehman, K D

    2009-01-01

    Dibutyltin (DBT), a widely used plastic stabilizer, has been detected in the environment as well as human tissues. Although teratological and developmental effects are well documented, there are no published reports of DBT effects on the developing nervous system. As part of a developmental neurotoxicity study of DBT, tissue samples were periodically collected to determine the distribution of total tin (Sn) in brain and whole blood. Pregnant Sprague-Dawley rats were exposed to 0, 10, or 25 ppm DBT in drinking water from gestational day (GD) 6 to weaning at postnatal day (PND) 21. Beginning on PND 3, half of the litters were directly dosed every 2 to 3 d via oral gavage with 0, 1, or 2.5 mg/kg DBT such that the dose level matched the water concentration (for example, litters with 25 ppm DBT in the water received 2.5 mg/kg). For Sn analysis, brain and blood samples were collected from culled pups on PND2 (males and females pooled), from pups (males and females separately) as well as dams at weaning (PND21), and from adult offspring (males and females) at PND93. Total Sn was quantified using inductively coupled plasma-mass spectroscopy (ICP-MS). At all ages, brain Sn levels were higher than blood. At culling, in the directly dosed pups at weaning, and in dams at weaning, Sn levels in both tissues were linearly related to dose. Weanling pups without direct dosing showed lower levels than either culled pups or dams, indicating that lactational exposure was minimal or negligible even while maternal exposure is ongoing. In the adults, Sn levels persisted in brains of directly dosed rats, and the high-dose females had higher levels than did high-dose males. No Sn was detected in adult blood. Thus, during maternal exposure to DBT in drinking water, Sn is placentally transferred to the offspring, but lactational transfer is minimal, if any. Furthermore, Sn is concentrated in brain compared to blood, and its elimination is protracted, on the order of days to months after

  18. A Search for Mitochondrial Damage in Alzheimer’s Disease Using Isolated Rat Brain Mitochondria

    PubMed Central

    Faizi, Mehrdad; Seydi, Enayatollah; Abarghuyi, Sadegh; Salimi, Ahmad; Nasoohi, Sanaz; Pourahmad, Jalal

    2016-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects regions of the brain that control cognition, memory, language, speech and awareness to one’s physical surroundings. The pathological initiation and progression of AD is highly complex and its prevalence is on the rise. In his study, Alzheimer's disease was induced with single injection of amyloid-β (Aβ) peptides (30ng, by stereotaxy) in each hemisphere of the Wistar rat brain. Then memory dysfunction, oxidative stress and apoptosis induced by Aβ peptide were investigated on isolated brain mitochondria obtained from infected rat. Our results showed memory impairment in rats after receiving an Aβ peptide. We also found significant rise (P<0.05) at ROS formation, mitochondrial membrane depolarization, mitochondria swelling, cytochrome c release and significant decrease in ATP/ADP ratio on mitochondria isolated from brain of these memory impaired rats compared with those of untreated control rat group. Activation of caspase-3 the final mediator of apoptosis in the brain homogenate of the memory impaired rats was another justification for occurrence of neuron loss in the experimental model of AD. Our results suggest that oxidative stress and mitochondria mediated apoptosis in brain neurons play very important role in initiation of AD. PMID:28228816

  19. Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

    PubMed

    Veraart, Jelle; Leergaard, Trygve B; Antonsen, Bjørnar T; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G Allan; Verhoye, Marleen; Sijbers, Jan

    2011-10-15

    Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

  20. Glutaric acid moderately compromises energy metabolism in rat brain.

    PubMed

    da C Ferreira, Gustavo; Viegas, Carolina M; Schuck, Patrícia F; Latini, Alexandra; Dutra-Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Vargas, Carmen R; Wajner, Moacir

    2005-12-01

    Glutaric acidemia type I is an inherited metabolic disorder biochemically characterized by tissue accumulation of predominantly glutaric acid (GA). Affected patients present frontotemporal hypotrophy, as well as caudate and putamen injury following acute encephalopathic crises. Considering that the underlying mechanisms of basal ganglia damage in this disorder are poorly known, in the present study we tested the effects of glutaric acid (0.2-5mM) on critical enzyme activities of energy metabolism, namely the respiratory chain complexes I-IV, succinate dehydrogenase and creatine kinase in midbrain of developing rats. Glutaric acid significantly inhibited creatine kinase activity (up to 26%) even at the lowest dose used in the assays (0.2mM). We also observed that CK inhibition was prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of GA was possibly mediated by oxidation of essential thiol groups of the enzyme. In addition, the activities of the respiratory chain complex I-III and of succinate dehydrogenase were also significantly inhibited by 20 and 30%, respectively, at the highest glutaric acid concentration tested (5mM). In contrast, complexes II-III and IV activities of the electron transport chain were not affected by the acid. The effect of glutaric acid on the rate of oxygen consumption in intact mitochondria from the rat cerebrum was also investigated. Glutaric acid (1mM) significantly lowered the respiratory control ratio (state III/state IV) up to 40% in the presence of the respiratory substrates glutamate/malate or succinate. Moreover, state IV respiration linked to NAD and FAD substrates was significantly increased in GA-treated mitochondria while state III was significantly diminished. The results indicate that the major metabolite accumulating in glutaric acidemia type I moderately compromises brain energy metabolism in vitro.

  1. Lipid mapping of the rat brain for models of disease.

    PubMed

    Martínez-Gardeazabal, J; González de San Román, E; Moreno-Rodríguez, M; Llorente-Ovejero, A; Manuel, I; Rodríguez-Puertas, R

    2017-02-21

    Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K(+) and PC (32: 0)+K(+) distributed primarily in gray matter, and PC (36: 1)+K(+) and PC (38: 1)+Na(+) distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K(+) in white matter, and PA (38: 5)+K(+) in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H(+) in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H(+) in white matter. Phosphatidylserines (PS): PS (34: 1)-H(+) in gray matter, and PS (38: 1)-H(+) in white matter. Sphingomyelin (SM

  2. Coupling between spontaneous pupillary fluctuations and brain activity relates to inattentiveness.

    PubMed

    Breeden, A L; Siegle, G J; Norr, M E; Gordon, E M; Vaidya, C J

    2017-01-01

    Autonomic activity in neurological and psychiatric disorders is often dysregulated, particularly in the context of attentional behaviors. This suggests that interplay between the autonomic nervous system and aspects of the central nervous system subserving attention may be disrupted in these conditions. Better understanding these interactions and their relationship with individual variation in attentional behaviors could facilitate development of mechanistic biomarkers. We identified brain regions defined by trait-sensitive central-autonomic coupling as a first step in this process. As spontaneous neural activity measured during the resting state is sensitive to phenotypic variability, unconfounded by task performance, we examined whether spontaneous fluctuations in brain activity and an autonomic measure, pupil diameter, were coupled during the resting state, and whether that coupling predicted individual differences in attentional behavior. By employing concurrent pupillometry and fMRI during the resting state, we observed positive coupling in regions comprising cingulo-opercular, default mode, and fronto-parietal networks, as well as negative coupling with visual and sensorimotor regions. Individuals less prone to distractibility in everyday behavior demonstrated stronger positive coupling in cingulo-opercular regions often associated with sympathetic activity. Overall, our results suggest that individuals less prone to distractibility have tighter intrinsic coordination between specific brain areas and autonomic systems, which may enable adaptive autonomic shifts in response to salient environmental cues. These results suggest that incorporating autonomic indices in resting-state studies should be useful in the search for biomarkers for neurological and psychiatric disorders.

  3. Effect of Cyclosporin A on the Uptake of D3-Selective PET Radiotracers in Rat Brain

    PubMed Central

    Tu, Zhude; Li, Shihong; Xu, Jinbin; Chu, Wenhua; Jones, Lynne A.; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    Introduction Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Methods Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. Results All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters. PMID:21718948

  4. KiSS-1 expression and metastin-like immunoreactivity in the rat brain.

    PubMed

    Brailoiu, G Cristina; Dun, Siok L; Ohsawa, Masahiro; Yin, Deling; Yang, Jun; Chang, Jaw Kang; Brailoiu, Eugen; Dun, Nae J

    2005-01-17

    Metastin, the gene product of metastasis suppressor gene KiSS-1, is the endogenous ligand for the G-protein-coupled receptor GPR54 (or AXOR12, or OT7T175). The expression of KiSS-1 gene and peptide and the distribution of metastin were studied in the rat central nervous system by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical methods. KiSS-1 gene and peptide expression was higher in the hypothalamus than in the brainstem and spinal cord. In the brain, metastin-like immunoreactivity (irMT) was found mainly in three groups of cells: dorsomedial hypothalamic nucleus, nucleus of the solitary tract, and caudal ventrolateral medulla. Immunoreactive fibers of varying density were noted in bed nucleus of stria terminalis, septal nuclei, nucleus accumbens, caudate putamen, diagonal band, amygdala, hypothalamus, zona incerta, thalamus, periaqueductal gray, raphe nuclei, lateral parabrachial nucleus, locus coeruleus, spinal trigeminal tract, rostral ventrolateral medulla, and medullary reticular nucleus. Preabsorption of the antiserum with metastin peptide fragment (45-54)-NH2 (1 microg/ml) resulted in no staining in any of the sections. The biological activity of metastin was assessed by monitoring intracellular calcium [Ca2+]i in cultured hippocampal neurons, which are known to express GPR54. Metastin increased [Ca2+]i in a population of cultured hippocampal neurons. The results show that metastin is biologically active in rat central neurons, and its anatomical distribution suggests a possible role in nociception and autonomic and neuroendocrine functions.

  5. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    PubMed

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.

  6. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    PubMed Central

    Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

  7. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

    PubMed

    Servatius, Richard J; Marx, Christine E; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D; Naylor, Jennifer C; Pang, Kevin C H

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  8. Cell-free DNA as a marker for prediction of brain damage in traumatic brain injury in rats.

    PubMed

    Ohayon, Sharon; Boyko, Matthew; Saad, Amit; Douvdevani, Amos; Gruenbaum, Benjamin F; Melamed, Israel; Shapira, Yoram; Teichberg, Vivian I; Zlotnik, Alexander

    2012-01-20

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early predictors of neurological outcomes are of great clinical importance. Cell free DNA (CFD), a biomarker used for the diagnosis and monitoring of several diseases, has been implicated as a possible prognostic indicator after TBI. The purpose of this study was to determine the pattern and timing of CFD levels after TBI, and whether a relationship exists between the level of CFD and brain edema and neurological outcomes. Thirty-nine Sprague-Dawley rats were randomly assigned to two groups: rats in group 1 (sham group) were anesthetized and had a scalp incision without TBI, and rats in group 2 were anesthetized and had a scalp incision with TBI, which was induced by using a weight drop model that causes diffuse brain injury. A neurological severity score (NSS) was assessed at 1, 24, and 48 h after TBI. CFD was measured via blood samples drawn at t=0 (baseline), 12, 24, 48, 72, and 120 h after TBI. At 48 h after TBI, brain edema was determined in a subgroup of 11 rats by calculating the difference between rats' wet and dry brain weight. The significance of comparisons between and within groups (CFD levels, brain water content, and NSS) were determined using the Kruskal-Wallis, Mann-Whitney and Student t test. The correlation between CFD levels and the NSS, as well as between CFD levels and the extent of brain edema, was calculated using the Spearman and Pearson tests, respectively. Compared with baseline levels, the CFD levels in rats subjected to TBI were significantly increased at 24 and 48 h after TBI (p<0.01 and p<0.05, respectively). A positive correlation was demonstrated between CFD levels 24 h following TBI and the extent of brain edema (r=0.63, p<0.05), as well as between CFD levels and the NSS (r=0.79, p<0.005). In this study, we demonstrated an increase in CFD levels after TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD levels may provide a

  9. Impairment of neurovascular coupling in type 1 diabetes mellitus in rats is linked to PKC modulation of BK(Ca) and Kir channels.

    PubMed

    Vetri, Francesco; Xu, Haoliang; Paisansathan, Chanannait; Pelligrino, Dale A

    2012-03-15

    We hypothesized that chronic hyperglycemia has a detrimental effect on neurovascular coupling in the brain and that this may be linked to protein kinase C (PKC)-mediated phosphorylation. Therefore, in a rat model of streptozotocin-induced chronic type 1 diabetes mellitus (T1DM), and in nondiabetic (ND) controls, we monitored pial arteriole diameter changes during sciatic nerve stimulation and topical applications of the large-conductance Ca(2+)-operated K(+) channel (BK(Ca)) opener, NS-1619, or the K(+) inward rectifier (Kir) channel agonist, K(+). In the T1DM vs. ND rats, the dilatory response associated with sciatic nerve stimulation was decreased by ∼30%, whereas pial arteriolar dilations to NS-1619 and K(+) were largely suppressed. These responses were completely restored by the acute topical application of a PKC antagonist, calphostin C. Moreover, the suffusion of a PKC activator, phorbol 12,13-dibutyrate, in ND rats was able to reproduce the vascular reactivity impairments found in T1DM rats. Assay of PKC activity in brain samples from T1DM vs. ND rats revealed a significant gain in activity only in specimens harvested from the pial and superficial glia limitans tissue, but not in bulk cortical gray matter. Altogether, these findings suggest that the T1DM-associated impairment of neurovascular coupling may be mechanistically linked to a readily reversible PKC-mediated depression of BK(Ca) and Kir channel activity.

  10. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Li, Lei; Wang, Lihong V.

    2015-01-01

    Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  11. Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

    PubMed

    Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

    2007-12-01

    The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain.

  12. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    PubMed

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB.

  13. Presynaptic localization of histamine H3-receptors in rat brain

    SciTech Connect

    Fujimoto, K.; Mizuguchi, H.; Fukui, H.; Wada, H. )

    1991-06-28

    The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a (3H) (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major (3H)(R) alpha-methylhistamine binding sites with increased specific activities ((3H)ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor (3H)(R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of (3H)(R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a (3H) yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors.

  14. Presence of corticotropin in brain of normal and hypophysectomized rats.

    PubMed Central

    Krieger, D T; Liotta, A; Brownstein, M J

    1977-01-01

    Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH. Images PMID:191820

  15. Brain neuronal chromatin responses in acute soman intoxicated rats.

    PubMed

    Martin, L J; Doebler, J A; Wall, T J; Shih, T M; Anthony, A

    1986-08-01

    Male Sprague-Dawley rats (200 g) were injected subcutaneously with soman, a potent neuronal acetylcholinesterase (AChE) inhibitor, at doses of 0.5, 0.8 and 1.0 LD50 (1 LD50 = 135 micrograms/kg) before decapitation at 1 and 24 h post-exposure. Correlative data were obtained on the severity of brain AChE inactivation and physicochemical changes in nuclear chromatin of cerebrocortical (layer V) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity; conversely, increases in F-DNA yield and chromophore area signify enhanced neuroexcitation. At 1 hr post-soman there was a dose-dependent inactivation of AChE with a moderate increase in chromatin activation, i.e., nuclear hypertrophy and chromatin dispersion. At 24 hr post-soman there was a partial restoration of AChE activity, notably in striatal neurons, with a suppression in chromatin template activity. These data indicate that actions of soman on neuronal functioning are time-dependent. The absence of any dose-related neuronal chromatin changes may signify existence of non-cholinergic mediated events.

  16. Xenon preconditioning reduces brain damage from neonatal asphyxia in rats.

    PubMed

    Ma, Daqing; Hossain, Mahmuda; Pettet, Garry K J; Luo, Yan; Lim, Ta; Akimov, Stanislav; Sanders, Robert D; Franks, Nicholas P; Maze, Mervyn

    2006-02-01

    Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3',5'-monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.

  17. (/sup 3/H)-beta-endorphin binding in rat brain

    SciTech Connect

    Houghten, R.A.; Johnson, N.; Pasternak, G.W.

    1984-10-01

    The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

  18. Robust automatic rodent brain extraction using 3-D pulse-coupled neural networks (PCNN).

    PubMed

    Chou, Nigel; Wu, Jiarong; Bai Bingren, Jordan; Qiu, Anqi; Chuang, Kai-Hsiang

    2011-09-01

    Brain extraction is an important preprocessing step for further processing (e.g., registration and morphometric analysis) of brain MRI data. Due to the operator-dependent and time-consuming nature of manual extraction, automated or semi-automated methods are essential for large-scale studies. Automatic methods are widely available for human brain imaging, but they are not optimized for rodent brains and hence may not perform well. To date, little work has been done on rodent brain extraction. We present an extended pulse-coupled neural network algorithm that operates in 3-D on the entire image volume. We evaluated its performance under varying SNR and resolution and tested this method against the brain-surface extractor (BSE) and a level-set algorithm proposed for mouse brain. The results show that this method outperforms existing methods and is robust under low SNR and with partial volume effects at lower resolutions. Together with the advantage of minimal user intervention, this method will facilitate automatic processing of large-scale rodent brain studies.

  19. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    PubMed

    Liu, J; Liu, L; Chen, H

    2011-05-05

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (p<0.01) and both of them were less so after taurine was supplemented (p<0.01). 2) Transmission electron microscopy revealed that brain cortex structures were sparse IUGR rats, showing many scattered apoptotic cells, decreased numbers of synapses, lower glial cell proliferation, and fewer neurons, more sparsely arranged, while these factors were significantly improved with taurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (p<0.001). 4) The results of immunohistochemistry showed that antenatal taurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (p<0.001). It can be concluded that it IUGR has a significant detrimental influence on the development of fetal rat brains, and antenatal supplement of taurine can significantly improve the IUGR

  20. [Semax prevents elevation of nitric oxide generation caused by incomplete global ischemia in the rat brain].

    PubMed

    Fadiukova, O E; Alekseev, A A; Bashkatova, V G; Tolordava, I A; Kuzenkov, V S; Mikoian, V D; Vanin, A F; Koshelev, V B; Raevskiĭ, K S

    2001-01-01

    A twofold increase in the nitric oxide (NO) production and a moderate increase in the content of secondary products of lipid peroxidation was observed in Wistar rats with incomplete global ischemia model induced by the bilateral occlusion of common carotid arteries. A clear correlation was observed between the NO content in the rat brain and the level of neurological disturbance manifestations in the ischemized animals. The synthetic peptide semax (a fragment of ACTH4-7 Pro-Gly-Pro) in a dose of 0.3 mg/kg prevented from the development of both neurological disturbances and excess NO production in the rat brain cortex.

  1. Effect of three anorectic drugs on brain GABA levels and synthesis in the Zucker rat.

    PubMed

    Orosco, M; Bremond, J; Jacquot, C; Cohen, Y

    1983-01-01

    1. Genetically obese Zucker rats and their lean littermates were submitted to a subchronic treatment with fenfluramine, mazindol and amphetamine. GABA levels and synthesis index were measured in different brain areas. 2. GABA levels, similar in obese and lean controls, were not changed after the three treatments. 3. A higher synthesis index of GABA was found in lean rats, in the striatum after mazindol and in the hypothalamus after amphetamine. 4. The three drugs increased the synthesis index of GABA in the remainder of the brain of both obese and lean rats.

  2. Reduced G-protein coupling to the GABAB receptor in the nucleus accumbens and the medial prefrontal cortex of the rat after chronic treatment with nicotine.

    PubMed

    Amantea, Diana; Tessari, Michela; Bowery, Norman G

    2004-01-30

    The effect of repeated administration of nicotine (0.4 mg/kg, daily, s.c., for 14 days) on GABAB receptor density, affinity and G-protein coupling was investigated in the mesocorticolimbic system of the rat brain. Baclofen-stimulated [35S]GTPgammaS binding autoradiography revealed that the level of G-protein coupling to GABAB receptors was significantly reduced in the medial prefrontal cortex and the nucleus accumbens of nicotine-treated rats as compared to vehicle-injected controls. By contrast, GABAB receptor density and affinity, as revealed by [3H]GABA saturation binding autoradiography, were not altered by the nicotine exposure in any of the regions examined. Reduced G-protein coupling to the GABAB receptor may result in disinhibition of mesocorticolimbic dopaminergic neurones, which would contribute to the development of sensitised dopaminergic responses to repeated administration of nicotine.

  3. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-05

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  4. Neuroanatomical mapping of juvenile rat brain regions with prominent basal signal in [(35)S]GTPgammaS autoradiography.

    PubMed

    Aaltonen, Niina; Palomäki, Ville A B; Lecklin, Anne; Laitinen, Jarmo T

    2008-03-01

    [(35)S]GTPgammaS autoradiography represents a powerful functional approach to detect receptor-dependent G(i/o) protein activity in anatomically defined brain structures. Inherent to this technique, however, is the notable basal signal evident in several brain regions in the absence of receptor stimulation by exogenously added agonist. In the rat brain, much of this basal labelling derives from tonic activation of adenosine A(1) and lysophosphatidic acid LPA(1) receptors in the gray and white matter regions, respectively. Despite the elimination of the two receptor activities, prominent basal [(35)S]GTPgammaS labelling is still evident in discrete brain structures, possibly reflecting regional enrichment of G(i/o) and/or constitutive receptor activity or the presence of still unknown endogenous ligands activating their orphan receptors. Here, the anatomical distribution of the enhanced basal signal was systematically mapped in brain sections of 4-week-old male Wistar rats. Regions with prominent basal [(35)S]GTPgammaS labelling represented neuroanatomically distinct structures, in particular various thalamic and hypothalamic nuclei. For instance, the paraventricular thalamic nucleus, the bed nucleus of the stria terminalis and the subfornical organ were highly labelled, as were the periaqueductal gray and the nucleus of the solitary tract. Pre-treatment with N-ethylmaleimide (NEM), an alkylating agent preventing all known receptor-driven G protein activity in cryostat sections markedly decreased the basal binding in all examined regions. In preliminary screening, selective antagonists for various brain-enriched G(i/o)-coupled receptors failed to suppress the basal signal in any of the studied regions.

  5. Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain.

    PubMed

    Arias, B; Arufe, M; Alfonso, M; Duran, R

    1995-04-01

    Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

  6. Spatial embedding of fMRI for investigating local coupling in human brain

    NASA Astrophysics Data System (ADS)

    Deshpande, Gopikrishna; LaConte, Stephen M.; Peltier, Scott; Hu, Xiaoping

    2005-04-01

    In this paper, we have investigated local spatial couplings in the human brain by applying nonlinear dynamical techniques on fMRI data. We have recorded BOLD-contrast echo-planar fMRI data along with high-resolution T1-weighted anatomical images from the resting brain of healthy human subjects and performed physiological correction on the functional data. The corrected data from resting subjects is spatially embedded into its phase space and the largest Lyapunov exponent of the resulting attractor is calculated and whole slice maps are obtained. In addition, we segment the high-resolution anatomical image and obtain a down sampled mask corresponding to gray and white matter, which is used to obtain mean indices of the exponents for both the tissues separately. The results show the existence of local couplings, its tissue specificity (more local coupling in gray matter than white matter) and dependence on the size of the neighborhood (larger the neighborhood, lesser the coupling). We believe that these techniques capture the information of a nonlinear and evolving system like the brain that may not be evident from static linear methods. The results show that there is evidence of spatio-temporal chaos in the brain, which is a significant finding hitherto not reported in literature to the best of our knowledge. We try to interpret our results from healthy resting subjects based on our knowledge of the native low frequency fluctuations in the resting brain and obtain a better understanding of the local spatial behavior of fMRI. This exploratory study has demonstrated the utility of nonlinear dynamical techniques like spatial embedding in analyzing fMRI data to gain meaningful insights into the working of human brain.

  7. Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

    PubMed

    Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

    2015-12-01

    Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.

  8. Focused ultrasound-induced blood-brain barrier disruption enhances the delivery of cytarabine to the rat brain.

    PubMed

    Zeng, Han-Qing; Lü, Lin; Wang, Feng; Luo, Yun; Lou, Shi-Feng

    2012-12-01

    To investigate the feasibility of using focused ultrasound (FUS) with microbubbles for targeted delivery of cytarabine to the brain. Sprague-Dawly rats (weighing 200-250 g) received focused ultrasound with intravenous injection microbubbles. At 0, 2, 4, 8, and 24 hours (n=5 for each time point) after sonication, animals received intravenous administration of cytarabine at a normal dose of 4 mg/kg body weight. Additional five rats were given with a high dose (50 mg/kg body weight) of cytarabine alone. Blood-brain barrier (BBB) permeability and cerebral cytarabine were determined. FUS in conjunction with microbubbles caused a transient BBB opening. Sonication exposure promoted cytarabine accumulation at the sonicated site. Animals injected with a normal dose of cytarabine 2 hours after sonication had similar concentrations of cerebral cytarabine compared to those with higher cytarabine without sonication. FUS can temporarily open the BBB and thus facilitate the penetration of systemic cytarabine into the brain.

  9. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation.

  10. Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats.

    PubMed

    Acar, Abdullah; Akil, Esref; Alp, Harun; Evliyaoglu, Osman; Kibrisli, Erkan; Inal, Ali; Unan, Fatma; Tasdemir, Nebahat

    2012-07-01

    To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.

  11. Optimization of choline administration regimen for correction of cognitive functions in rats after brain injury.

    PubMed

    Guseva, M V; Kamenskii, A A; Gusev, V B

    2013-06-01

    Choline diet promotes improvement of the brain cognitive functions in rats with moderate-to-severe traumatic brain injury. In previous studies, the rats received choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior to and 2 weeks after experimental brain injury. To the end of the experiments (in 4 weeks), the post-traumatic disturbances in the cognitive functions were observed in both groups, although they were less pronounced than in the rats kept on the choline-supplemented diet. Based on original mathematical model, this paper proposes a method to calculate the most efficient use of choline to correct the brain cognitive functions. In addition to evaluating the cognitive functions, the study assessed expression of α7 nicotinic acetylcholine receptors, the amount of consumed food and water, and the dynamics of body weight.

  12. Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

    NASA Astrophysics Data System (ADS)

    Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

    1998-07-01

    The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

  13. Imaging brain activity during seizures in freely behaving rats using a miniature multi-modal imaging system

    PubMed Central

    Sigal, Iliya; Koletar, Margaret M.; Ringuette, Dene; Gad, Raanan; Jeffrey, Melanie; Carlen, Peter L.; Stefanovic, Bojana; Levi, Ofer

    2016-01-01

    We report on a miniature label-free imaging system for monitoring brain blood flow and blood oxygenation changes in awake, freely behaving rats. The device, weighing 15 grams, enables imaging in a ∼ 2 × 2 mm field of view with 4.4 μm lateral resolution and 1 − 8 Hz temporal sampling rate. The imaging is performed through a chronically-implanted cranial window that remains optically clear between 2 to > 6 weeks after the craniotomy. This imaging method is well suited for longitudinal studies of chronic models of brain diseases and disorders. In this work, it is applied to monitoring neurovascular coupling during drug-induced absence-like seizures 6 weeks following the craniotomy. PMID:27699123

  14. Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry

    PubMed Central

    Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko

    2016-01-01

    Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID:27355350

  15. Imaging of sialidase activity in rat brain sections by a highly sensitive fluorescent histochemical method.

    PubMed

    Minami, Akira; Shimizu, Hirotaka; Meguro, Yuko; Shibata, Naoki; Kanazawa, Hiroaki; Ikeda, Kiyoshi; Suzuki, Takashi

    2011-09-01

    Sialidase (EC 3.2.1.18) removes sialic acid from sialoglycoconjugates. Since sialidase extracellularly applied to the rat hippocampus influences many neural functions, including synaptic plasticity and innervations of glutamatergic neurons, endogenous sialidase activities on the extracellular membrane surface could also affect neural functions. However, the distribution of sialidase activity in the brain remains unknown. To visualize extracellular sialidase activity on the membrane surface in the rat brain, acute brain slices were incubated with 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB (FRV LB) at pH 7.3. After 1h, myelin-abundant regions showed intense fluorescence in the rat brain. Although the hippocampus showed weak fluorescence in the brain, mossy fiber terminals in the hippocampus showed relatively intense fluorescence. These fluorescence intensities were attenuated with a sialidase-specific inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA, 1mM). Additionally, the fluorescence intensities caused by X-Neu5Ac and FRV LB were correlated with the sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac), a classical substrate for quantitative measurement of sialidase activity, in each brain region. Therefore, staining with X-Neu5Ac and FRV LB is specific for sialidase and useful for quantitative analysis of sialidase activities. The results suggest that white matter of the rat brain has intense sialidase activity.

  16. Dichloroacetate increases glucose use and decreases lactate in developing rat brain

    SciTech Connect

    Miller, A.L.; Hatch, J.P.; Prihoda, T.J. )

    1990-12-01

    Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase. Neutralized DCA (100 mg/kg) or saline was intravenously administered to 20 to 25-day-old rats (50-75g). Fifteen minutes later a mixture of {sup 6-14}C glucose and {sup 3}H fluorodeoxyglucose (FDG) was administered intravenously and the animals were sacrificed by microwave irradiation (2450 MHz, 8.0 kW, 0.6-0.8 sec) after 2 or 5 min. Brain regional rates of glucose use and metabolite levels were determined. DCA-treated rats had increased rates of glucose use in all regions studied (cortex, thalamus, striatum, and brain stem), with an average increase of 41%. Lactate levels were lower in all regions, by an average of 35%. There were no significant changes in levels of ATP, creatine phosphate, or glycogen in any brain region. Blood levels of lactate did not differ significantly between the DCA- and the saline-treated groups. Blood glucose levels were higher in the DCA group. In rats sacrificed by freeze-blowing, DCA treatment caused lower brain levels of both lactate and pyruvate. These results cannot be explained by any systemic effect of DCA. Rather, it appears that in the immature rat, DCA treatment results in activation of brain PDH, increased metabolism of brain pyruvate and lactate, and a resulting increase in brain glycolytic rate.

  17. Exploring neuro-vascular and neuro-metabolic coupling in rat somatosensory cortex

    NASA Astrophysics Data System (ADS)

    Mesquita, R. C.; Huppert, T. J.; Boas, D. A.

    2009-01-01

    The existence of a coupling between changes in neuronal activity, cerebral blood flow and blood oxygenation is well known. The explicit relationship between these systems, however, is complex and remains a subject of intense research. Here, we use direct electrophysiological recordings to predict blood flow and oxygenation changes measured with optical methods during parametric stimulation applied to the somatosensory cortex in rat brain. Using a multimodal model of the cerebral functional unit, we estimate a neuro-vascular and a neuro-metabolic transfer function relating the experimentally measured neural responses with the inputs to a vascular model predicting hemodynamic and blood oxygenation changes. We show that our model can accurately predict experimentally measured parametric hemodynamic evoked responses by using a single linear transfer function relationship with a reduced number of state parameters to relate the level of neural activity to evoked cerebral blood flow and oxygen metabolism changes. At the same time, we characterize the metabolic and vascular neural response functions and interpret their physiological significance.

  18. Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation in the rat brain.

    PubMed

    Bediz, Cem Seref; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim; Oztekin, Esma

    2006-02-01

    Extremely low-frequency (0-300 Hz) electromagnetic fields (EMFs) generated by power lines, wiring and home appliances are ubiquitous in our environment. All populations are now exposed to EMF, and exposure to EMF may pose health risks. Some of the adverse health effects of EMF exposure are lipid peroxidation and cell damage in various tissues. This study has investigated the effects of EMF exposure and zinc administration on lipid peroxidation in the rat brain. Twenty-four male Sprague-Dawley rats were randomly allocated to three groups; they were maintained untreated for 6 months (control, n = 8), exposed to low-frequency (50 Hz) EMF for 5 minutes every other day for 6 months (n = 8), or exposed to EMF and received zinc sulfate daily (3 mg/kg/day) intraperitoneally (n = 8). We measured plasma levels of zinc and thiobarbituric acid reactive substances (TBARS), and levels of reduced glutathione (GSH) in erythrocytes. TBARS and GSH levels were also determined in the brain tissues. TBARS levels in the plasma and brain tissues were higher in EMF-exposed rats with or without zinc supplementation, than those in controls (p < 0.001). In addition, TBARS levels were significantly lower in the zinc-supplemented rats than those in the EMF-exposed rats (p < 0.001). GSH levels were significantly decreased in the brain and erythrocytes of the EMF-exposed rats (p < 0.01), and were highest in the zinc-supplemented rats (p < 0.001). Plasma zinc was significantly lower in the EMF-exposed rats than those in controls (p < 0.001), while it was highest in the zinc-supplemented rats (p < 0.001). The present study suggests that long-term exposure to low-frequency EMF increases lipid peroxidation in the brain, which may be ameliorated by zinc supplementation.

  19. Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

    PubMed

    Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

    2016-11-01

    Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

  20. Effect of manganese on the concentration of amino acids in different regions of the rat brain.

    PubMed

    Lipe, G W; Duhart, H; Newport, G D; Slikker, W; Ali, S F

    1999-01-01

    The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains.

  1. Involvement of Nuclear Related Factor 2 Signaling Pathway in the Brain of Obese Rats and Obesity-Resistant Rats Induced by High-Fat Diet.

    PubMed

    Ma, Wei-Wei; Ding, Bing-Jie; Wang, Li-Jing; Shao, Yi; Xiao, Rong

    2016-04-01

    We aimed to investigate the mechanism of brain damage in diet-induced obese (DIO) rats and diet-resistant (DR) rats from the viewpoint of redox state and nuclear related factor 2 (Nrf2) signaling pathway. Sprague-Dawley rats were fed with a high-fat diet for 10 weeks to obtain the DIO and DR rats. d-Galactose was injected subcutaneously through the back of the neck for 10 weeks to establish oxidative stress model rats. Then, the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and the level of glutathione peroxidase (GSH-Px) in serum and brain tissue were measured by using enzymatic assay kits. The levels of cholecystokinin and peptide YY in the brain tissue were detected by using enzyme-linked immunosorbent assay kits. In addition, the protein expression of Nrf2 and its downstream factors such as heme oxygenase 1, manganese superoxide dismutase, and NAD(P)H quinone oxidoreductase 1 (NQO1) in the brain tissue were measured by Western blotting. In the brain of DIO rats, the level of GSH and ratio of GSH/GSSG were lower, whereas the GSH-Px concentration was higher compared with DR rats significantly. On the other hand, the GSSG level was higher in the serum of DIO rats compared with the DR rats. The oxidative stress state in the brain of DIO rats, but not in DR rats, were observed. In addition, the protein expressions of Nrf2 and NQO1 were downregulated in the brain of DR rats compared with that in DIO rats. Our data suggest that the Nrf2/NQO1 signaling pathway and redox state were involved in the pathogenesis of the rats prone to obesity, but not the DR rats resistant to obesity.

  2. Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

    PubMed Central

    Yarowsky, P J; Krueger, B K; Olson, C E; Clevinger, E C; Koos, R D

    1991-01-01

    The expression of mRNAs coding for the alpha subunit of rat brain and rat heart sodium channels has been studied in adult and neonatal rat cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). Rat brain sodium channel subtype I, II, IIA, and III sequences were simultaneously amplified in the same PCR using a single oligonucleotide primer pair matched to all four subtype sequences. Identification of each subtype-specific product was inferred from the appearance of unique fragments when the product was digested with specific restriction enzymes. By using this RT-PCR method, products arising from mRNAs for all four brain sodium channel subtypes were identified in RNA extracted from adult rat cerebral cortex. The predominant component was type IIA with lesser levels of types I, II, and III. In contrast, the type II and IIA sequences were the predominant RT-PCR products in neonatal rat cortex, with slightly lower levels of type III and undetectable levels of type I. Thus, from neonate to adult, type II mRNA levels decrease relative to type IIA levels. Using a similar approach, we detected mRNA coding for the rat heart sodium channel in neonatal and adult rat cerebral cortex and in adult rat heart. These results reveal that mRNAs coding for the heart sodium channel and all four previously sequenced rat brain sodium channel subtypes are expressed in cerebral cortex and that type II and IIA channels may be differentially regulated during development. Images PMID:1658783

  3. Real-time monitoring of brain tissue oxygen using a miniaturized biotelemetric device implanted in freely moving rats.

    PubMed

    Bazzu, Gianfranco; Puggioni, Giulia G M; Dedola, Sonia; Calia, Giammario; Rocchitta, Gaia; Migheli, Rossana; Desole, Maria S; Lowry, John P; O'Neill, Robert D; Serra, Pier A

    2009-03-15

    A miniaturized biotelemetric device for the amperometric detection of brain tissue oxygen is presented. The new system, derived from a previous design, has been coupled with a carbon microsensor for the real-time detection of dissolved O(2) in the striatum of freely moving rats. The implantable device consists of a single-supply sensor driver, a current-to-voltage converter, a microcontroller, and a miniaturized data transmitter. The oxygen current is converted to a digital value by means of an analog-to-digital converter integrated in a peripheral interface controller (PIC). The digital data is sent to a personal computer using a six-byte packet protocol by means of a miniaturized 434 MHz amplitude modulation (AM) transmitter. The receiver unit is connected to a personal computer (PC) via a universal serial bus. Custom developed software allows the PC to store and plot received data. The electronics were calibrated and tested in vitro under different experimental conditions and exhibited high stability, low power consumption, and good linear response in the nanoampere current range. The in vivo results confirmed previously published observations on oxygen dynamics in the striatum of freely moving rats. The system serves as a rapid and reliable model for studying the effects of different drugs on brain oxygen and brain blood flow and it is suited to work with direct-reduction sensors or O(2)-consuming biosensors.

  4. Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats.

    PubMed

    Pintana, Hiranya; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-08-01

    It is unclear whether the dipeptidyl peptidase 4 (DPP4) inhibitor can counteract brain insulin resistance, brain mitochondrial dysfunction, impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived obese rats. We hypothesized that DPP4 inhibitor vildagliptin improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. Thirty male Wistar rats received either a sham-operated (S, n=6) or bilateral orchiectomy (ORX, n=24). ORX rats were divided into two groups and fed with either a normal diet (ND (NDO)) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n=6/subgroup) to receive either a vehicle or vildagliptin (3 mg/kg per day, p.o.) for 4 weeks. After treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined in each rat. We found that HFO rats exhibited peripheral and brain insulin resistance, brain mitochondrial dysfunction, impaired hippocampal synaptic plasticity and cognitive decline. NDO rats did not develop peripheral and brain insulin resistance. However, impaired hippocampal synaptic plasticity and cognitive decline occurred. Vildagliptin significantly improved peripheral insulin sensitivity, restored brain insulin sensitivity and decreased brain mitochondrial reactive oxygen species production in HFO rats. However, vildagliptin did not restore hippocampal synaptic plasticity and cognitive function in both NDO and HFO rats. These findings suggest that vildagliptin could not counteract the impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived subjects, despite its effects on improved peripheral and brain insulin sensitivity as well as brain mitochondrial function.

  5. Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization.

    PubMed

    Bonaccorso, A; Musumeci, T; Serapide, M F; Pellitteri, R; Uchegbu, I F; Puglisi, G

    2017-03-18

    Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave <250nm) of opposite surface charge in different areas of the brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan. Physico-chemical and technological characterizations of poly-l-lactide-co-glycolide (negative) and chitosan/poly-l-lactide-co-glycolide (positive) fluorescent labeled nanoparticles were performed. The animals were allocated to three groups receiving negative and positive polymeric nanoparticles via single intranasal administration or no treatment. The localization of both nanocarriers in different brain areas was detected using fluorescent microscopy. Our data revealed that both nanocarriers reach the brain and are able to persist in the brain up to 48h after intranasal administration. Surface charge influenced the involved pathways in their translocation from the nasal cavity to the central nervous system. The positive charge of nanoparticles slows down brain reaching and the trigeminal pathway is involved, while the olfactory pathway may be responsible for the transport of negatively charged nanoparticles, and systemic pathways are not excluded.

  6. Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Yang, Xinmai

    2011-03-01

    Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

  7. A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury

    PubMed Central

    Kim, Ho Jeong

    2017-01-01

    Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat’s skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury. PMID:28070456

  8. Monoclonal antibodies against type II rat brain protein kinase

    SciTech Connect

    Nakabayashi, C.H.; Huang, K.P.

    1987-05-01

    Three monoclonal antibodies (8/1, 10/10, and 25/3) against rat brain type II protein kinase C (PKC) were used to carry out the immunochemical characterization of this kinase. These antibodies immunoprecipitated the type II PKC in a dose-dependent manner but did neither to type I nor type III isozyme. Purified type II PKC has a molecular weight of 82,000 and consists of heterogeneous isoelectric point species, all of which are cross reactive with these antibodies. Immunoblot analysis of the tryptic fragments from PKC revealed that all three antibodies recognized the 33-38-KDa fragments, the phospholipid/phorbol ester-binding domain, but not the 45-48-KDa fragments, the kinase catalytic domain. The immune complexes of the kinase and the antibodies retained the kinase activity which was dependent on Ca/sup 2 +/ and phosphatidylserine (PS) and further activated by diacylglycerol. With antibody 8/1, the apparent Km values of the kinase for Ca/sup 2 +/ and PS were not influenced. The initial rate and final extent of autophosphorylation were reduced. The concentration of PS required for half-maximal (/sup 3/H)phorbol 12,13-dibutyrate (PDBu) binding was increased and the total PDBu binding was reduced. In the presence of optimum concentrations of Ca/sup 2 +/ and PS, the Kd of PDBu was unaffected by the antibody but the total binding was reduced. These results demonstrate that the PS/PDBu-binding domain contains the major epitope for the antibodies and the antibody mainly influences the PS/PDBu binding to the kinase.

  9. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    PubMed Central

    Abdelalim, Essam M.; Bellier, Jean-Pierre; Tooyama, Ikuo

    2016-01-01

    Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and dorsal root ganglion (DRG). BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the DH of the spinal cord and in the neurons of the intermediate column (IC) and ventral horn (VH). Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I–II) labeled with calcitonin gene-related peptide (CGRP), suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase (ChAT) in the motor neurons of the VH. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NP receptor-A (NPR-A) and/or NP receptor-B (NPR-B) at the spinal cord level. PMID:27994541

  10. Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

    PubMed

    Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

    2015-02-01

    Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians.

  11. N-acetylcysteine attenuates copper overload-induced oxidative injury in brain of rat.

    PubMed

    Ozcelik, Dervis; Uzun, Hafize; Nazıroglu, Mustafa

    2012-06-01

    Copper is an integral part of many important enzymes involved in a number of vital biological processes. Even though it is essential to life, at elevated tissue concentrations, copper can become toxic to cells. Recent studies have reported oxidative damage due to copper in various tissues. Considering the vulnerability of the brain to oxidative stress, this study was undertaken to explore possible beneficial antioxidant effects of N-acetylcysteine on oxidative stress induced by copper overload in brain tissue of rats. Thirty-two Wistar rats were equally divided into four groups. The first group was used as control. The second, third, and fourth groups were given 1 g/L copper in their drinking water for 1 month. At the end of this period, the group 2 rats were sacrificed. During the next 2 weeks, the rats in group 3 were injected intraperitoneally with physiological saline and those in group 4 with 20 mg/kg intraperitoneal injections of N-acetylcysteine. In group 2 the lipid peroxidation and nitric oxide levels were increased in the brain cortex while the activities of superoxide dismutase and catalase and the concentration of glutathione were decreased. In rats treated with N-acetylcysteine, lipid peroxidation decreased and the activities of antioxidant enzyme improved in the brain cortex. In conclusion, treatment with N-acetylcysteine modulated the antioxidant redox system and reduced brain oxidative stress induced by copper.

  12. Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury

    PubMed Central

    Wang, Yang; Zhang, Chunhu; Peng, Weijun; Xia, Zian; Gan, Pingping; Huang, Wei; Shi, Yafei; Fan, Rong

    2016-01-01

    Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography-tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI. PMID:27599591

  13. Methylene blue improves brain oxidative metabolism and memory retention in rats.

    PubMed

    Callaway, Narriman Lee; Riha, Penny D; Bruchey, Aleksandra K; Munshi, Zeenat; Gonzalez-Lima, F

    2004-01-01

    Methylene blue (MB) increases mitochondrial oxygen consumption and restores memory retention in rats metabolically impaired by inhibition of cytochrome c oxidase. This study tested two related hypotheses using biochemical and behavioral techniques: (1) that low-level MB would enhance brain cytochrome c oxidation, as tested in vitro in brain homogenates and after in vivo administration to rats and (2) that corresponding low-dose MB would enhance spatial memory retention in normal rats, as tested 24 h after rats were trained in a baited holeboard maze for 5 days with daily MB posttraining injections. The biochemical in vitro studies showed an increased rate of brain cytochrome c oxidation with the low but not the high MB concentrations tested. The in vivo administration studies showed that the corresponding MB low dose (1 mg/kg) increased brain cytochrome c oxidation 24 h after intraperitoneal injection, but not after 1 or 2 h postinjection. In the behavioral studies, spatial memory retention in probe trials (percentage of visits to training-baited holes compared to total visits) was significantly better for MB-treated than saline control groups (66% vs. 31%). Together the findings suggest that low-dose MB enhances spatial memory retention in normal rats by increasing brain cytochrome c oxidase activity.

  14. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

    PubMed

    Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

    2014-01-01

    The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats.

  15. Extremely low frequency magnetic fields induce oxidative stress in rat brain.

    PubMed

    Manikonda, Pavan K; Rajendra, Pilankatta; Devendranath, D; Gunasekaran, B; Channakeshava; Aradhya, Shivakumara R S; Sashidhar, Rao B; Subramanyam, Chivukula

    2014-01-01

    The present investigation was conducted to understand the influence of long-term exposure of rats to extremely low frequency magnetic fields (ELF-MF), focusing on oxidative stress (OS) on different regions of rat's brain. Male Wistar rats (21-day-old) were exposed to ELF-MF (50 Hz; 50 and 100 µT) for 90 days continuously; hippocampal, cerebellar and cortical regions from rats were analyzed for (i) reactive oxygen species (ROS), (ii) metabolites indicative of OS and (iii) antioxidant enzymes. In comparison to control group rats, the rats that were continuously exposed to ELF-MF caused OS and altered glutathione (GSH/GSSG) levels in dose-dependent manner in all the regions of the brain. Accumulation of ROS, lipid peroxidation end products and activity of superoxide dismutase in different regions was in the descending order of cerebellum < hippocampus < cortex. Decrement in GSH/GSSG levels and increment in glutathione peroxidase activity were in the descending order of hippocampus < cerebellum < cortex. The continuous exposure to ELF-MF caused OS in all the examined regions of brain more significantly at 100 µT than at 50 µT. Varied influences observed in different regions of the brain, as documented in this study, may contribute to altered metabolic patterns in its related regions of the central nervous system, leading to aberrant neuronal functions.

  16. L-histidine but not D-histidine attenuates brain edema following cryogenic injury in rats.

    PubMed

    Ikeda, Y; Mochizuki, Y; Matsumoto, H; Nakamura, Y; Dohi, K; Jimbo, H; Shimazu, M; Hayashi, M; Matsumoto, K

    2000-01-01

    Oxygen free radicals have been implicated in the genesis of traumatic brain injury and brain edema (BE). Recent studies have suggested that hydroxyl radical can initiate lipid peroxidation, thus producing lipid-free radicals that may become important sources of singlet oxygen. L-histidine, a singlet oxygen scavenger, potentially can be used to treat BE. In this study we investigated the effects of L-histidine and D-histidine on BE following cryogenic injury in rats. Male Wistar rats were anaesthetized with chloral hydrate. Vasogenic BE was produced by a cortical freezing lesion. Generation of singlet oxygen from photoactivation of rose bengal was studied by electron spin resonance (ESR). Animals were separated into four groups: sham rats (n = 5), saline-treated rats (n = 10), L-histidine treated rats (n = 6) and D-histidine treated rats (n = 7). Each agent (100 mg/kg) was administered intravenously at 30 minutes before lesion production. Animals were sacrificed at 24 hours after lesion production and the brain water content was determined by the dry-wet weight method. L-histidine had no effect on rectal and brain temperature. Election Spin Resonance studies demonstrated that L-histidine is a singlet oxygen scavenger. L-histidine but not D-histidine significantly attenuated BE following cryogenic injury (p < 0.05). In conclusion, L-histidine is useful in the treatment of traumatic BE.

  17. Probing Intrinsic Resting-State Networks in the Infant Rat Brain

    PubMed Central

    Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

    2016-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

  18. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    NASA Astrophysics Data System (ADS)

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-01

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  19. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    SciTech Connect

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-10

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  20. St. John's Wort increases brain serotonin synthesis by inhibiting hepatic tryptophan 2, 3 dioxygenase activity and its gene expression in stressed rats.

    PubMed

    Bano, Samina; Ara, Iffat; Saboohi, Kausar; Moattar, Tariq; Chaoudhry, Bushra

    2014-09-01

    We aimed to investigate the effects of herbal St. John's Wort (SJW) on transcriptional regulation of hepatic tryptophan 2, 3 - dioxygenase (TDO) enzyme activity and brain regional serotonin (5-HT) levels in rats exposed to forced swim test (FST). TDO mRNA expression was quantified using real-time reverse transcription polymerase chain (RT-PCR) reaction and brain regional indoleamines were determined by high performance liquid chromatography coupled to fluorescence detector. Behavioral analysis shows significant reduction in immobility time in SJW (500mg/kg/ml) administered rats. It was found that pretreatment of SJW to rats did not prevent stress-induced elevation in plasma corticosterone levels however it increases serotonin synthesis by virtue of inhibiting hepatic TDO enzyme activity and its gene expression, ascertaining the notion that there exists an inverse relationship between hepatic TDO enzyme activity and brain 5-HT. The drug also decreases serotonin turnover in all the brain areas (hypothalamus, hippocampus amygdala) in stressed rats endorsing its monoamine oxidase inhibition property. Inhibition of TDO enzyme activity and its gene expression by the drug provides new insights for the development of therapeutic interventions for stress related mental illnesses.

  1. Forebrain and brain stem neural circuits contribute to altered sympathetic responses to heating in senescent rats.

    PubMed

    Kenney, Michael J; Fels, Richard J

    2003-11-01

    Acute heating in young rats increases visceral sympathetic nerve discharge (SND); however, renal and splanchnic SND responses to hyperthermia are attenuated in senescent compared with young Fischer 344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). Central mechanisms by which aging alters visceral SND responses to heating are unknown. We tested the hypothesis that forebrain neural circuits are involved in suppressing sympathoexcitatory responses to heating in chloralose-anesthetized, senescent F344 rats. Renal and splanchnic SND responses to increased (38 degrees C-41 degrees C) internal temperature were determined in midbrain-transected (MT) and sham-MT young (3-mo-old), mature (12-mo-old), and senescent (24-mo-old) F344 rats and in cervical-transected (CT) and sham-CT senescent rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats but was increased in CT senescent rats. Splanchnic SND responses to heating were higher in MT vs. sham-MT senescent rats and in CT vs. MT senescent rats. SND responses to heating were similar in MT and sham-MT young and mature rats. Mean arterial pressure (MAP) was increased during heating in MT but not in sham-MT senescent rats, whereas heating-induced increases in MAP were higher in sham-MT vs. MT young rats. These data suggest that in senescent rats suppression of splanchnic SND to heating involves forebrain and brain stem neural circuits, whereas renal suppression is mediated solely by brain stem neural circuits. These results support the concept that aging alters the functional organization of pathways regulating SND and arterial blood pressure responses to acute heating.

  2. Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

    PubMed

    Fares, Raafat P; Belmeguenai, Amor; Sanchez, Pascal E; Kouchi, Hayet Y; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S; Bezin, Laurent

    2013-01-01

    Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

  3. Using on-line solid phase extraction for in vivo speciation of diffusible ferrous and ferric iron in living rat brain extracellular fluid.

    PubMed

    Su, Cheng-Kuan; Chen, Yi-Ting; Sun, Yuh-Chang

    2017-02-08

    Exploration of brain extracellular non-protein-bound/diffusible iron species remains a critically important issue in investigations of free radical biology and neurodegenerative diseases. In this study, a facile sample pretreatment scheme, involving poly(vinyl chloride)-metal ion interactions as a selective extraction procedure, was optimized in conjunction with microdialysis (MD) sampling and inductively coupled plasma mass spectrometry (ICP-MS) in cool-plasma mode for in vivo online monitoring of rat brain extracellular Fe(II) and Fe(III) species. Optimization of the system provided detection limits in the range 0.9-6.9 μg Fe L(-1), based on a 12-μL microdialysate, for the tested iron species; relative standard deviations of the signal intensities during 7.8 h of continuous measurement were less than 9.4%-sufficient to determine the basal concentrations of rat brain extracellular Fe(II) and Fe(III) species and to describe their dynamic actions. The method's applicability was verified through (i) spike analyses of offline-collected rat brain microdialysates, (ii) determination of the basal Fe(II) and Fe(III) concentrations of living rat brain extracellular fluids, and (iii) monitoring of the dynamic changes in the Fe(II) and Fe(III) concentrations in response to perfusion of a high-K(+) medium. This proposed sample pretreatment scheme, based on polymer-metal ion interactions and hyphenation to an MD sampling device and an ICP-MS system, appears to have great practicality for the online monitoring of rat brain extracellular diffusible iron species.

  4. An autoradiographic map of (3H)diprenorphine binding in rat brain: effects of social interaction

    SciTech Connect

    Panksepp, J.; Bishop, P.

    1981-10-01

    (3H)Diprenorphine binding was analyzed autoradiographically in the brains of 33 day old rat pups. A photographic atlas of diprenorphine binding in the coronal plane is provided to highlight the dispersion of opioid receptor systems through the brain. To determine whether brain opioid release may be induced by social interactions, half the animals were sacrificed following a 30 min period of social interaction while the other half were sacrificed following 30 min of social isolation. Opioid binding was higher in isolate-tested animals than socially-tested ones, suggesting that social interaction may promote endogenous brain opioid release.

  5. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-11-01

    Long noncoding RNAs (lncRNAs) are ≥200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 weeks) compared to both immature (4 weeks) and old (70 weeks) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  6. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-12-01

    Long noncoding RNAs (lncRNAs) are ≥ 200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 week) compared to both immature (4 week) and old (70 week) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  7. Enalapril attenuates ischaemic brain oedema and protects the blood-brain barrier in rats via an anti-oxidant action.

    PubMed

    Panahpour, Hamdollah; Dehghani, Gholam Abbas; Bohlooli, Shahab

    2014-03-01

    1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. Vehicle and a non-hypotensive dose of enalapril (0.03 mg/kg) were administered at the beginning of the reperfusion period. A neurological deficit score (NDS) was determined for all rats at the end of the reperfusion period. Then, brain oedema formation was investigated using the wet-dry weight method and BBB permeability was evaluated on the basis of extravasation of Evans blue (EB) dye. In addition, oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA) in brain homogenates. 3. Inhibition of ACE by enalapril significantly reduced NDS and decreased brain oedema formation (P < 0.05 for both). Disruption of the BBB following ischaemia resulted in considerable leakage of EB dye into the brain parenchyma of the ipsilateral hemispheres of vehicle-treated rats. Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions.

  8. Azotemia (48 h) decreases the risk of brain damage in rats after correction of chronic hyponatremia.

    PubMed

    Soupart, A; Penninckx, R; Stenuit, A; Decaux, G

    2000-01-03

    Brain myelinolysis complicates excessive correction of chronic hyponatremia in man. Myelinolysis appear in rats for correction levels deltaSNa) > 20 mEq/l/24 h. We previously showed in rats that when chronic hyponatremia was corrected with urea, the incidence and the severity of brain lesions were significantly reduced compared to hypertonic saline. In man, hyponatremia is frequently associated with azotemia and hemo-dialysis usually corrects rapidly the serum sodium (SNa) but only few patients apparently develop demyelination. We hypothesize that uremic state protects brain against myelinolysis. This hypothesis was evaluated in rats developing azotemia by administration of mercuric chloride (HgCl2, 1.5 mg/kg). Severe (SNa < 120 mEq/l) hyponatremia (3 days) was induced by S.C. AVP and i.p. 2.5% D-glucose for 3 days. HgCl2 was injected on day 2. Hyponatremia was corrected on day 4 by i.p. injections of 5% NaCl in order to obtain a correction level largely above the toxic threshold for brain (deltaSNA approximately 30 mEq/l/24 h). Surviving rats were decapitated on day 10 for brain analysis. In the group with renal failure (Group I, n = 15, urea 59 mmol/l) the outcome was remarkably favourable with only three rats (3/15) dying before day 10 and only one of them (1/3) presenting myelinolysis-related neurologic symptoms. The 12 other rats (80%) survived in Group I without symptoms and brain analysis was normal in all of them despite large correction level (deltaSNa: 32 mEq/l/24 h). On the contrary in nine rats in which HgCl, did not produce significant azotemia (control 1, n = 9, urea: 11 mmol/l), all the rats developed severe neurologic symptoms and eight of them died before day 10. Similar catastrophic outcome was observed in the non-azotemic controls (control 2, no HgCl2 administration, n = 15, urea: 5 mmol/l). All of them developed myelinolysis-related neurologic symptoms and only four of them survived with severe brain lesions (survival 12/15 in Group I vs. 5

  9. Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

    PubMed

    Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

    2012-05-10

    Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury.

  10. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    PubMed

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  11. Brain-derived neurotrophic factor-modified umbilical cord mesenchymal stem cell transplantation improves neurological deficits in rats with traumatic brain injury.

    PubMed

    Yuan, Yuan; Pan, Shumao; Sun, Zhaoming; Dan, Qiqin; Liu, Jia

    2014-07-01

    This study explored the effect of brain-derived neurotrophic factor (BDNF) gene-modified umbilical cord mesenchymal stem cell (UCMSC) transplantation on neurological functional improvement in rats after brain trauma. A rat model of cerebral contusion in the motor-sensory cortex was established by the weight hammer-falling method. UCMSCs were cultured and transferred with BDNF gene. After determining BDNF expression and activity, the BDNF gene-modified UCMSCs were implanted into brains of rats receiving the brain injury. The neurological function was evaluated 1 and 2 weeks after brain injury. BDNF expression was then determined by immunohistochemistry. Severe neurological dysfunction was observed in animals subjected to contusion brain injury (10.50 ± 0.53). A significant improvement in neurological function was found in the UCMSC transplantation animals (7.75 ± 0.71) compared with the brain injury only group (p < 0.01). Rats with BDNF gene-modified UCMSCs showed the highest improvement in behavior (5.50 ± 0.76; p < 0.01). BDNF gene-modified UCMSCs can survive and migrate in rat cerebral tissues. The transplantation of these UCMSCs can improve the neurological functions of rats with traumatic brain injury.

  12. Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin.

    PubMed

    Petrosillo, G; Matera, M; Casanova, G; Ruggiero, F M; Paradies, G

    2008-11-01

    Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.

  13. Metabolism and disposition of 3,6-dibutanoylmorphine in rat brain.

    PubMed

    Tasker, R A; Nakatsu, K

    1986-09-01

    In previous studies from this laboratory it was found that dibutanoylmorphine (DBM) was more potent than morphine as an analgesic in rats and that it was less active than acetyl esters of morphine on behaviour. As DBM is a morphine prodrug, the aim of this work was to determine if rat brain homogenates were capable of deacylating DBM and monobutanoylmorphine (MBM) and to determine relative proportions of parent drug to metabolites in the brain in vivo. In 10% (w/v) brain homogenates, DBM was eliminated with a half-life of about 70 min (corrected for dilution), while MBM was eliminated 10 times as quickly. DBM and its metabolites were found in both blood and brain as early as 1 min after i.v. administration of DBM. After 5 min, the predominant form in blood was MBM and in brain it was DBM. Thus, rat brain possesses the capacity to metabolize DBM by deesterification and the parent drug, MBM, and morphine were found in blood and brain in vivo.

  14. Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain

    PubMed Central

    Kim, Hyung-Wook; Rao, Jagadeesh S; Rapoport, Stanley I.; Igarashi, Miki

    2010-01-01

    Background Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase A2 (cPLA2) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent iPLA2 VIA. Assuming that these enzyme changes represented brain homeostatic responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would produce changes in the opposite directions. Methods Brain expression of PUFA-metabolizing enzymes and their transcription factors was quantified in male rats fed an n-6 PUFA adequate or deficient diet for 15 weeks post-weaning. Results The deficient compared with adequate diet increased brain mRNA, protein and activity of iPLA2 VIA and 15-lipoxygenase (LOX), but decreased cPLA2 IVA and COX-2 expression. The brain protein level of the iPLA2 transcription factor SREBP-1 was elevated, while protein levels were decreased for AP-2α and NF-κB p65, cPLA2 and COX-2 transcription factors, respectively. Conclusions With dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of their transcription factors change in a way that would homeostatically dampen reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA metabolizing enzyme expression is increased. The changes correspond to reported in vitro enzyme selectivities for AA compared with DHA. (198 words) PMID:21070866

  15. Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development.

    PubMed

    Ghosh, Payel; Mukherjee, Nabanita; Ghosh, Krishnendu; Mallick, Suvadip; Pal, Chiranjib; Laskar, Aparna; Ghosh, Anirban

    2015-09-01

    The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed.

  16. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    PubMed

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  17. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    PubMed Central

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Effect of Piper betle leaf extract on alcoholic toxicity in the rat brain.

    PubMed

    Saravanan, R; Rajendra Prasad, N; Pugalendi, K V

    2003-01-01

    The protective effect of Piper betle, a commonly used masticatory, has been examined in the brain of ethanol-administered Wistar rats. Brain of ethanol-treated rats exhibited increased levels of lipids, lipid peroxidation, and disturbances in antioxidant defense. Subsequent to the experimental induction of toxicity (i.e., the initial period of 30 days), aqueous P. betle extract was simultaneously administered in three different doses (100, 200, and 300 mg kg(-1)) for 30 days along with the daily dose of alcohol. P. betle coadministration resulted in significant reduction of lipid levels (free fatty acids, cholesterol, and phospholipids) and lipid peroxidation markers such as thiobarbituric acid reactive substances and hydroperoxides. Further, antioxidants, like reduced glutathione, vitamin C, vitamin E, superoxide dismutase, catalase, and glutathione peroxidase, were increased in P. betle-coadministered rats. The higher dose of extract (300 mg kg(-1)) was more effective, and these results indicate the neuroprotective effect of P. betle in ethanol-treated rats.

  1. Large-Scale Brain Network Coupling Predicts Total Sleep Deprivation Effects on Cognitive Capacity

    PubMed Central

    Wang, Lubin; Zhai, Tianye; Zou, Feng; Ye, Enmao; Jin, Xiao; Li, Wuju; Qi, Jianlin; Yang, Zheng

    2015-01-01

    Interactions between large-scale brain networks have received most attention in the study of cognitive dysfunction of human brain. In this paper, we aimed to test the hypothesis that the coupling strength of large-scale brain networks will reflect the pressure for sleep and will predict cognitive performance, referred to as sleep pressure index (SPI). Fourteen healthy subjects underwent this within-subject functional magnetic resonance imaging (fMRI) study during rested wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Self-reported scores of sleepiness were higher for TSD than for RW. A subsequent working memory (WM) task showed that WM performance was lower after 36 h of TSD. Moreover, SPI was developed based on the coupling strength of salience network (SN) and default mode network (DMN). Significant increase of SPI was observed after 36 h of TSD, suggesting stronger pressure for sleep. In addition, SPI was significantly correlated with both the visual analogue scale score of sleepiness and the WM performance. These results showed that alterations in SN-DMN coupling might be critical in cognitive alterations that underlie the lapse after TSD. Further studies may validate the SPI as a potential clinical biomarker to assess the impact of sleep deprivation. PMID:26218521

  2. Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

    PubMed Central

    Thompson, Scott J; Millecamps, Magali; Aliaga, Antonio; Seminowicz, David A; Low, Lucie A; Bedell, Barry J; Stone, Laura S; Schweinhardt, Petra; Bushnell, M Catherine

    2014-01-01

    Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the Spared Nerve Injury (SNI) model of neuropathic pain and the formalin pain model in rats using Positron Emission Tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30 min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3 weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats were scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving

  3. Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain.

    PubMed

    Thompson, Scott J; Millecamps, Magali; Aliaga, Antonio; Seminowicz, David A; Low, Lucie A; Bedell, Barry J; Stone, Laura S; Schweinhardt, Petra; Bushnell, M Catherine

    2014-05-01

    Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents.

  4. Effects of atrial and brain natriuretic peptides upon cyclic GMP levels, potassium transport, and receptor binding in rat astrocytes

    SciTech Connect

    Beaumont, K.; Tan, P.K. )

    1990-02-01

    The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des(gl18, ser19, gly20, leu21, gly22) ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors. ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.

  5. Intracellular pathways regulating ciliary beating of rat brain ependymal cells

    PubMed Central

    Nguyen, Thien; Chin, Wei-Chun; O’Brien, Jennifer A; Verdugo, Pedro; Berger, Albert J

    2001-01-01

    The mammalian brain ventricles are lined with ciliated ependymal cells. As yet little is known about the mechanisms by which neurotransmitters regulate cilia beat frequency (CBF). Application of 5-HT to ependymal cells in cultured rat brainstem slices caused CBF to increase. 5-HT had an EC50 of 30 μM and at 100 μM attained a near-maximal CBF increase of 52.7 ± 4.1 % (mean ± s.d.) (n= 8). Bathing slices in Ca2+-free solution markedly reduced the 5-HT-mediated increase in CBF. Fluorescence measurements revealed that 5-HT caused a marked transient elevation in cytosolic Ca2+ ([Ca2+]c) that then slowly decreased to a plateau level. Analysis showed that the [Ca2+]c transient was due to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores; the plateau was probably due to extracellular Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. Application of ATP caused a sustained decrease in CBF. ATP had an EC50 of about 50 μM and 100 μM ATP resulted in a maximal 57.5 ± 6.5 % (n= 12) decrease in CBF. The ATP-induced decrease in CBF was unaffected by lowering extracellular [Ca2+], and no changes in [Ca2+]c were observed. Exposure of ependymal cells to forskolin caused a decrease in CBF. Ciliated ependymal cells loaded with caged cAMP exhibited a 54.3 ± 7.5 % (n= 9) decrease in CBF following uncaging. These results suggest that ATP reduces CBF by a Ca2+-independent cAMP-mediated pathway. Application of 5-HT and adenosine-5′-O-3-thiotriphosphate (ATP-γ-S) to acutely isolated ciliated ependymal cells resulted in CBF responses similar to those of ependymal cells in cultured slices suggesting that these neurotransmitters act directly on these cells. The opposite response of ciliated ependymal cells to 5-HT and ATP provides a novel mechanism for their active involvement in central nervous system signalling. PMID:11179397

  6. Ionizing Radiation Alters the Properties of Sodium Channels in Rat Brain Synaptosomes

    DTIC Science & Technology

    1986-01-01

    International So, iet% for Ncurochemistry SIonizing Radiation Alters the Properties of Sodium to Channels in Rat Brain Synaptosomes Michael J. Mullin, Walter...its binding site in the channel, Ionizing radiation reduced radiation on the voltage-sensitive sodium channels in rat the veratridine-stimulated...in the order of membrane lipids. Key greatest. Batrachotoxin-stimulated 22Na’ uptake was Words: Ionizing radiation- Sodium channels-Mem- less sensitive

  7. Leukotriene C4 in the rat brain after resuscitation from clinical death.

    PubMed

    Kapuściński, A

    1994-01-01

    By means of the radioimmunological method changes of concentration of leukotriene C4 (LTC4) in rat brain cortex and hippocampus have been evaluated during 5-min clinical death and up to 2 h after resuscitation. Wet weight/dry weight methodology was utilized to evaluate brain water content. Ischemia did not produce significant changes of LTC4 concentration in the brain. In the postresuscitation period concentration of LTC4 in both brain regions significantly increased reaching in 5 and 15 min respectively a 4- and 5-fold control values. Later the concentration of LTC4 in the brain decreased reaching in 30 min a 3-fold control level, and in 60 and 120 min after resuscitation control values. Water content after resuscitation did not show significant changes in both brain regions. LTC4 does not seem to play an important role in the development of cerebral edema.

  8. Brain monoamine metabolism is altered in rats following spontaneous, long-distance running.

    PubMed

    Elam, M; Svensson, T H; Thorén, P

    1987-06-01

    Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise.

  9. Effect of clozapine on the metabolism of serotonin in rat brain.

    PubMed

    Ruch, W; Asper, H; Bürki, H R

    1976-01-01

    Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleep-inducing properties of this drug.

  10. Element distribution in the brain sections of rats measured by synchrotron radiation X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Liu, N. Q.; Zhang, F.; Wang, X. F.; Zhang, Z. Y.; Chai, Z. F.; Huang, Y. Y.; He, W.; Zhao, X. Q.; Zuo, A. J.; Yang, R.

    2004-02-01

    The concentration of trace elements in brain sections was measured by synchrotron radiation X-ray fluorescence. The relative concentration was calculated by means of the normalization of Compton scattering intensity approximately 22 keV, after the normalization for collecting time of X-ray spectrum and the counting of the ion chamber, and subtracting the contribution of the polycarbonate film for supporting sample. Furthermore, the statistical evaluation of the element distribution in various regions of the brain sections of the 20-day-old rats was tested. For investigating the distribution of elements in the brain of iodine deficient rats, Wistar rats were fed with iodine deficient diet and deionized water (ID group). The rats were fed the same iodine deficient diet, but drank KIO 3 solution as control (CT group). The results showed that the contents of calcium (Ca) in thalamus (TH) and copper (Cu) and iron (Fe) in cerebral cortex (CX) of ID rats were significantly lower than that of control rats, while the contents of phosphor (P), sulfur (S), potassium (K), rubidium (Rb), bromine (Br), chlorine (Cl), zinc (Zn), Ca and Cu of ID in hippocampus (H) and the contents of Br, Cl, Zn and Ca in cerebral cortex of ID rats were significantly higher. Especially, the difference of Br, Cl, Zn and Ca in H between ID and CT was more significant. The contents of all elements measured in H were higher than (or equal to) CX and/or TH for both groups, except low Cl of the control rats. Furthermore Zn and Cu contents along the hippocampal fissure in both groups were 1.5 ( P<0.001) and 0.87( P<0.03) times higher than in hippocampus, respectively. Considering the results of cluster analysis our study shows that the marked alterations in the spatial distribution of Zn and Ca of ID rats brain during brain development stages. In addition, the effect of the perfusion with 0.9% NaCl solution before taking brain on the distribution of elements in the brain sections was observed and

  11. [GABA reuptake by rat brain slices in hypokinesia and under the influence of cinnarizine and flunarizine].

    PubMed

    Mirzoian, N R; Akopian, V P; Kocharian, A Zh; Knarian, V A; Arakelian, L N; Gevorkian, G A

    1998-01-01

    Studies showed that 15-day restriction of motor activity inhibits the reuptake of GABA by sections of the rat brain cortex and hypothalamus. In prolonged intraperitoneal injection of 10 mg/kg cinnarizine in hyperkinesia, further inhibition of this process in hypothalamic sections is encountered on the 15th days. Flunarizin (1 mg/kg) administered in a like manner has no significant effect on GABA reuptake. A course of GABA injections in a dose of 5 mg/kg improves in rats with restricted motor activity the local blood flow in the frontal lobe of the brain.

  12. [Effect of semax and mexidol on brain ischemia models in rats].

    PubMed

    Iasnetsov, V V; Voronina, T A

    2009-01-01

    It was established that semax and mexidol significantly reduced neurological deficiency and increased the survival in rats with model brain ischemia induced by the bilateral ligation of common carotid arteries. Mexidol exhibited a linear dose-effect relationship (in a range of doses from 30 to 120 mg/kg per day), while the effect of semax decreased with increasing dose (in a dose range from 0.3 to 1.2 mg/kg per day). Preventive course administration of semax and mexidol considerably reduced neurologic deficiency and amnesia in a step-down passive avoidance situation in rats with model brain ischemia caused by gravitation overload.

  13. Imaging of water distribution in the rat brain by activation autoradiography

    SciTech Connect

    Kogure, K.; Kawashima, K.; Iwata, R.; Ido, T. )

    1990-01-01

    Regional water distribution in the rat brain was obtained autoradiographically by activation analysis. The autoradiogram obtained for the normal rat brain showed high accumulation of water in the areas of sensory-motor cortex, hippocampus, thalamus, and amygdaloid cortex, whereas corpus callosum and internal capsule showed low water contents as expected. The estimated values of water content were 78.6 +/- 4.9 weight % for gray matter, and 73.5 +/- 4.9 weight % for white matter, respectively. The mean values of the water content were consistent with those obtained by a conventional drying-weighing method.

  14. Prevention of brain infarction by postischemic administration of histidine in rats.

    PubMed

    Adachi, Naoto; Liu, Keyue; Arai, Tatsuru

    2005-03-28

    Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

  15. In vivo brain microdialysis studies on the striatal dopamine and serotonin release in zitter mutant rats.

    PubMed

    Yoshimoto, Kanji; Nishimura, Akira; Hattori, Hiroyuki; Joyce, Jeffery N; Yoshida, Toshihide; Hioki, Chizuko; Kogure, Akinori; Ueda, Shuichi

    2006-07-01

    In the present study, using in vivo brain microdialysis, we investigated the basal extracellular dopamine (DA) and serotonin (5-HT) release in the caudal striatum (cSTR) of young (4-6 months old) and aged (10-12 months old) zitter mutant rats. The basal extracellular levels of DA release in both young and aged zitter rats were significantly lower than that of age-matched Sprague-Dawley (SD) rats, whereas only aged zitter rats showed a significant difference in the basal 5-HT release. Dopaminergic neurons were more vulnerable than serotonergic neurons in the cSTR of zitter mutant rats during aging. Perfusion of 60 mM potassium (K+) enhanced the extracellular levels of cSTR DA in the young zitter rats and the extracellular levels of both DA and 5-HT in the cSTR of the aged zitter rats. The firing rate of K+-stimulated monoamine release in the cSTR was significantly higher in the zitter rats than in the age-matched SD rats. These findings suggest that there are innate quantitative differences in the releasable pool and the availability of monoamines in the cSTR of zitter mutant rats.

  16. 26Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    NASA Astrophysics Data System (ADS)

    Yumoto, Sakae; Nagai, Hisao; Kakimi, Shigeo; Matsuzaki, Hiroyuki

    2010-04-01

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used 26Al as a tracer, and measured 26Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, 26AlCl 3 was subcutaneously injected into pregnant rats. Considerable amounts of 26Al were measured in the tissues of newborn rats immediately after birth. The amounts of 26Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of 26Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  17. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    PubMed Central

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M.; Farr, Tracy D.; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent. PMID:25100993

  18. Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat

    PubMed Central

    Deli, Levente; Gajári, Dávid; Dávid, Szabolcs; Pozsgay, Zsófia; Hegedűs, Nikolett; Tihanyi, Károly; Liposits, Zsolt

    2014-01-01

    The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does

  19. Changes of Noradrenaline in Brain Homogenate of Rats with Brain Injury Secondary to Intracerebral Hemorrhage: A Study of the Mechanism

    PubMed Central

    Xu, Zhi-Qiang; Zhou, Hua-Dong; Jiang, Xiao-Jiang; Wang, Jing-Zhou; Chen, Man-E

    2005-01-01

    Objective: To observe the changes of noradrenaline (NE) content dynamically in the homogenate of rat brain tissues during experimental intracerebral hemorrhage (ICH), so as to understand the role of NE in secondary brain injury. Methods: Seventy Wistar rats were randomly assigned into sham operation group and ICH group, each group subdivided into different time phase points as pre-operation, 0.5, 6, 12, 24, 48 and 72 h post-operation groups (n=5). ICH model was established by injection of collagenase and heparin into rat caudate nucleus, and the changes of NE content in the peripheral tissues of the hematoma, hypothalamus and brainstem were observed respectively at following time points as before operation and 0.5, 6, 12, 48 and 72 h after the operation. NE was determined by high-performance liquid chromatography. Results: NE activities in the peripheral tissues of the hematoma, hypothalamus and brainstem increased synchronously 0.5 h after operation, peaked at 24 h, and then began to decline at 48 h. At the same time, the neurobehavioral score varied synchronously together with NE. Conclusion: NE is involved in the pathogenesis of secondary damage of the brain during ICH. PMID:23674956

  20. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

    PubMed

    Marmarou, A; Foda, M A; van den Brink, W; Campbell, J; Kita, H; Demetriadou, K

    1994-02-01

    This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

  1. Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke-exposed rats.

    PubMed

    Ramesh, Thiyagarajan; Sureka, Chandrabose; Bhuvana, Shanmugham; Begum, Vavamohaideen Hazeena

    2015-08-01

    Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect.

  2. Aging and sex influence the permeability of the blood-brain barrier in the rat

    SciTech Connect

    Saija, A.; Princi, P.; D'Amico, N.; De Pasquale, R.; Costa, G.

    1990-01-01

    The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer ({sup 14}C)-{alpha}-aminoisobutyric acid. The authors observed that: (a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; (b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; (c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging and sex-related alterations in thee permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.

  3. Measurement of the optical properties of rat brain tissue using contact spatially resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Gysbrechts, Barbara; Nguyen Do Trong, Nghia; Wang, Ling; Cabral, Henrique; Navratilova, Zaneta; Battaglia, Francesco P.; Saeys, Wouter; Bartic, Carmen

    2014-05-01

    Nowadays, biophotonics is widely used in neuroscience. The effectiveness of biophotonic techniques, such as fluorescence imaging and optogenetics, is affected by the optical properties of the examined tissue. Therefore, knowledge of these properties is essential to carefully plan experiments. Mice and rats are widely used in neuroscience studies. However, reports about optical properties of their brains are very rare. We measured optical absorption μa and reduced scattering μ's coefficients of native rat brain in the visible and near-infrared wavelength region, using contact spatially resolved spectroscopy (SRS). In this study, we estimate μa and μ's for the rat cortex and discuss their stability in time. Additionally, variations in optical properties within and between samples were characterized. The results extend the range of known optical properties for the rat cortex, especially in the visible range, relevant to optogenetics. μa and μ's are stable within a time span of four hours, and show low variation in and between brain samples. This indicates that a suitable protocol was used to estimate optical properties of rodent brain tissue. Since contact SRS is a non-destructive method, this technique could be used also to measure μa and μ's in living animals. Moreover, the probe has small dimensions, allowing the characterization of optical properties in different structures of the brain.

  4. Cerebrovascular responses of the rat brain to noxious stimuli as examined by functional near-infrared whole brain imaging

    PubMed Central

    He, Ji-Wei; Tian, Fenghua; Liu, Hanli

    2012-01-01

    While near-infrared (NIR) spectroscopy has been increasingly used to detect stimulated brain activities with an advantage of dissociating regional oxy- and deoxyhemoglobin concentrations simultaneously, it has not been utilized much in pain research. Here, we investigated and demonstrated the feasibility of using this technique to obtain whole brain hemodynamics in rats and speculated on the functional relevance of the NIR-based hemodynamic signals during pain processing. NIR signals were emitted and collected using a 26-optodes array on rat's dorsal skull surface after the removal of skin. Following the subcutaneous injection of formalin (50 μl, 3%) into a hindpaw, several isolable brain regions showed hemodynamic changes, including the anterior cingulate cortex, primary/secondary somatosensory cortexes, thalamus, and periaqueductal gray (n = 6). Time courses of hemodynamic changes in respective regions matched with the well-documented biphasic excitatory response. Surprisingly, an atypical pattern (i.e., a decrease in oxyhemoglobin concentration with a concomitant increase in deoxyhemoglobin concentration) was seen in phase II. In a separate group of rats with innocuous brush and noxious pinch of the same area (n = 11), results confirmed that the atypical pattern occurred more likely in the presence of nociception than nonpainful stimulation, suggesting it as a physiological substrate when the brain processes pain. In conclusion, the NIR whole brain imaging provides a useful alternative to study pain in vivo using small-animal models. Our results support the notion that neurovascular response patterns depend on stimuli, bringing attention to the interpretation of vascular-based neuroimaging data in studies of pain. PMID:22378174

  5. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  6. Influence of volatile anesthetics on muscarinic receptor adenylate cyclase coupling in brain and heart

    SciTech Connect

    Anthony, B.L.

    1988-01-01

    In the present study, the influence of four volatile anesthetics (enflurane, isoflurane, diethyl ether, and chloroform) on (1) muscarinic receptor binding parameters and (2) muscarnic regulation of adenylate cyclase activity was examined using membranes isolated from rat brain and heart. Membranes were equilibrated with each of the four anesthetics for 30 minutes and then during the binding assay. The data obtained can be summarized as follows: (1) volatile anesthetics increased receptor affinity for a radiolabeled antagonists, ({sup 3}H)N-methylscopolamine (({sup 3}H)MS), by decreasing its rate of dissociation in brain stem, but not in cardiac, membranes, (2) volatile anesthetics decreased high affinity ({sup 3}H)Oxotremorine-M binding, (3) volatile anesthetics depressed or eliminated the guanine nucleotide sensitivity of agonist binding. The influence of volatile anesthetics on muscarinic regulation of adenylate cyclase enzyme activity was studied using {alpha}({sup 32}P)ATP as the substrate.

  7. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    PubMed

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  8. Chronic exposure of gestation rat to sevoflurane impairs offspring brain development.

    PubMed

    Wang, Yuheng; Cheng, Yongxia; Liu, Guibo; Tian, Xiaodan; Tu, Xuefeng; Wang, Junke

    2012-06-01

    Recently it was demonstrated that the exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors can trigger widespread apoptotic neurodegeneration. Sevoflurane is a new inhalation anesthetic agent commonly used in the clinic. Here we address whether sevoflurane could induce neurotoxicity in the developing brain. Sevoflurane was administered to rats before pregnancy and pregnant rats on embryonic days E6, E10, E14, and E18 1MAC for 6 h, and we employed histopathological, immunochemistry, semiquantitative RT-PCR, and Western blot to investigate the effect of the exposure of pregestation and gestation rats to sevoflurane on the offspring brain development. The results showed that the exposure of gestation but not pregestation rats to sevoflurane-induced extensive apoptotic neurodegeneration in the hippocampus of offspring at P0, P7, and P14, accompanied by altered expression of casepase-3, GAP-43, nNOS, NMDAR1, NMDAR2A, and NMDAR2B. Furthermore, upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein levels were observed in the hippocampus of offspring at P0, P7, and P14 from rats exposed to sevoflurane at gestation, but not pregestation. In summary, our data suggest that sevoflurane induces developmental neurotoxicity in rats and this may be attributed to the upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein in the hippocampus.

  9. The rate of training response to aerobic exercise affects brain function of rats.

    PubMed

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p < 0.05). On the reverse Morris Maze test HRT-trained rats outperformed HRT control ones. Significant difference was noted between LRT and HRT groups in redox milieu as assessed by levels of reactive oxygen species (ROS), carbonylation of proteins, nNOS and S-nitroso-cysteine. Moreover the silent information regulator 1 (SIRT1), brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.

  10. Stress-sensitive arterial hypertension, hemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

    PubMed

    Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

    2017-03-08

    The study of early development of the arterial hypertension in association with emotional stress is of great importance for better understanding of etiolody and pathogenesis of the hypertensive disease. MRI technique was applied to evaluate the hemodynamic and brain metabolites changes in 1- and 3-Mo-old ISIAH rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive WAG rats (8 male rats). In the 3-Mo-old ISIAH rats, age-dependent increase in the blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of abdominal aorta. The renal vascular resistance in the ISIAH rats decreased while aging, though, at both ages it remained higher than the renal vascular resistance in WAG rats. Integral metabolome portrait demonstrated that hypertension development in the ISIAH rats was associated with attenuation of excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats, the opposite age-dependent changes were observed. In contrast, in hypothalamus of 3-Mo-old ISIAH rats, an increase in energetic activity and prevalence of excitatory neurotransmitters over inhibitory was noticed. The blood flow through the main arteries showed positive correlation with glutamate and glutamine levels in hypothalamus, and negative one - with hypothalamic GABA level. The blood pressure values positively correlated with hypothalamic choline levels. Thus, the early development of the stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. This article is protected by copyright. All rights reserved.

  11. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    EPA Pesticide Factsheets

    Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups.This dataset is associated with the following publication:Pandya, J.D., J. Royland , R.C. McPhail, P.G. Sullivan, and P. Kodavanti. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats. NEUROBIOLOGY OF AGING. Elsevier Science Ltd, New York, NY, USA, 42: 25-34, (2016).

  12. Reductions in Calcium Uptake Induced in Rat Brain Synaptosomes by Ionizing Radiation

    DTIC Science & Technology

    1991-01-01

    was also reduced by radiation exposure. Nimodipine binding to dihydropyridine (DHP) L-type calcium uptake after irradiation in wh31e-brain, cortical...TERIz. and L.. GANDIA. Dihydropyridine Bay K 8644 aetivates chro- 2-32-286 (1950). mall’in cell calcium channels.Nature 309. 69-71 (1984). 33. E. L...TRIGGLE. Bay K 8644. a I .4-dihv- of dihydropyridine -sensitive calcium channels in rat brain synapto- dropyridinc Ca> channel activator: Dissociation

  13. Brain structure volumes in the mole rat, Spalax ehrenbergi (Spalacidae, Rodentia) in comparison to the rat and subterrestrial insectivores.

    PubMed

    Frahm, H D; Rehkämper, G; Nevo, E

    1997-01-01

    Natural blindness and a subterranean, digging mode of life demand peculiar adaptations of the central nervous system in the mole rat Spalax ehrenbergi, which are the focus of this quantitative investigation. Volumes of 25 brain structures in Spalax were evaluated allometrically, using the least encephalized mammalian species, the Madagassian hedgehog-like tenrecs (Tenrecinae) as a reference base, and their sizes compared with those of the rat (as a more generalized representative of rodents) and of some subterranean Insectivora. The allometric approach reveals that Spalax has a larger brain than tenrecs and the rat. Within the brain, the neocortex and diencephalon are well developed, an observation also made in other mammalian species with a relatively high encephalization. An unique feature in Spalax is the enlargement of motor structures of the brain, such as the cerebellum (and cerebellar nuclei), and the striatum. Most conspicuous is the large size of the nucleus motorius nervi trigemini, reflecting the importance of masticatory muscles for the special digging technique, which demand an intense use of the teeth for loosening the soil.

  14. In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

    PubMed

    Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

    1997-09-19

    The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

  15. Moderate Hypothermia Inhibits Brain Inflammation and Attenuates Stroke-induced Immunodepression in Rats

    PubMed Central

    Gu, Li-Juan; Xiong, Xiao-Xing; Ito, Takashi; Lee, Jessica; Xu, Bao-Hui; Krams, Sheri; Steinberg, Gary K.; Zhao, Heng

    2013-01-01

    Summary Aims Stroke causes both brain inflammation and immunodepression. Mild to moderate hypothermia is known to attenuate brain inflammation but its role in stroke-induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation. Methods Stroke was induced in rats by permanent distal MCA occlusion combined with transient bilateral CCA occlusion while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T cell proliferation assays and confocal microscopy were used to study SIID and brain inflammation. Results Brief Intra-Ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen, and enhanced T cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited mRNA expression of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO+ cells) and macrophages (CD68+ cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation. Conclusions Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation. PMID:23981596

  16. Image segmentation by EM-based adaptive pulse coupled neural networks in brain magnetic resonance imaging.

    PubMed

    Fu, J C; Chen, C C; Chai, J W; Wong, S T C; Li, I C

    2010-06-01

    We propose an automatic hybrid image segmentation model that integrates the statistical expectation maximization (EM) model and the spatial pulse coupled neural network (PCNN) for brain magnetic resonance imaging (MRI) segmentation. In addition, an adaptive mechanism is developed to fine tune the PCNN parameters. The EM model serves two functions: evaluation of the PCNN image segmentation and adaptive adjustment of the PCNN parameters for optimal segmentation. To evaluate the performance of the adaptive EM-PCNN, we use it to segment MR brain image into gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The performance of the adaptive EM-PCNN is compared with that of the non-adaptive EM-PCNN, EM, and Bias Corrected Fuzzy C-Means (BCFCM) algorithms. The result is four sets of boundaries for the GM and the brain parenchyma (GM+WM), the two regions of most interest in medical research and clinical applications. Each set of boundaries is compared with the golden standard to evaluate the segmentation performance. The adaptive EM-PCNN significantly outperforms the non-adaptive EM-PCNN, EM, and BCFCM algorithms in gray mater segmentation. In brain parenchyma segmentation, the adaptive EM-PCNN significantly outperforms the BCFCM only. However, the adaptive EM-PCNN is better than the non-adaptive EM-PCNN and EM on average. We conclude that of the three approaches, the adaptive EM-PCNN yields the best results for gray matter and brain parenchyma segmentation.

  17. Establishment and identification of a hypoxia-ischemia brain damage model in neonatal rats

    PubMed Central

    YAO, DAN; ZHANG, WEIRAN; HE, XUE; WANG, JINHU; JIANG, KEWEN; ZHAO, ZHENGYAN

    2016-01-01

    The present study was designed to set up a reliable model of severe hypoxia-ischemia brain damage (HIBD) in neonatal rats and several methods were used to identify whether the model was successful. A total of 40 healthy 7-day-old Sprague-Dawley rats were randomly divided into 2 groups: The sham-surgery group (n=18) and the HIBD model group (n=22). The HIBD model was produced according to the traditional Rice method. The rats were anesthetized with ethyl ether. The left common carotid artery (CCA) was exposed, ligated and cut. Following this, the rats were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2 h. In the sham-surgery group, the left CCA was exposed but was not ligated, cut or exposed to hypoxia. The neurobehavioral changes of the rats were observed in the 24 h after HIBD. The brains were collected after 72 h to observe the pathological morphological changes of the brain tissue. The behavioral ability and neurobehavioral changes were studied in each group. The water maze test was used for evaluating the learning-memory ability when the rats were 28 days old. Compared with the sham-surgery group, all the HIBD model rats had a lag of motor development. The rats had evident changes in anatomy and Nissl staining, and cognitive impairment was shown through the result of the water maze. Therefore, the model of HIBD in neonatal rats is feasible and provides a reliable model for subsequent studies. PMID:27073628

  18. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury.

    PubMed

    Lim, Yi Wei; Meyer, Nathan P; Shah, Alok S; Budde, Matthew D; Stemper, Brian D; Olsen, Christopher M

    2015-01-01

    Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI), even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC) and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions) and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure.

  19. Blast overpressure induces shear-related injuries in the brain of rats exposed to a mild traumatic brain injury

    PubMed Central

    2013-01-01

    Background Blast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Results Rats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions. Conclusions These lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted. PMID:24252601

  20. Tracking of Magnetite Labeled Nanoparticles in the Rat Brain Using MRI

    PubMed Central

    Martínez Vera, Naira P.; Schmidt, Reinhold; Langer, Klaus; Zlatev, Iavor; Wronski, Robert; Auer, Ewald; Havas, Daniel; Windisch, Manfred; von Briesen, Hagen; Wagner, Sylvia; Stab, Julia; Deutsch, Motti; Pietrzik, Claus; Fazekas, Franz; Ropele, Stefan

    2014-01-01

    This study was performed to explore the feasibility of tracing nanoparticles for drug transport in the healthy rat brain with a clinical MRI scanner. Phantom studies were performed to assess the R1 ( =  1/T1) relaxivity of different magnetically labeled nanoparticle (MLNP) formulations that were based on biodegradable human serum albumin and that were labeled with magnetite of different size. In vivo MRI measurements in 26 rats were done at 3T to study the effect and dynamics of MLNP uptake in the rat brain and body. In the brain, MLNPs induced T1 changes were quantitatively assessed by T1 relaxation time mapping in vivo and compared to post-mortem results from fluorescence imaging. Following intravenous injection of MLNPs, a visible MLNP uptake was seen in the liver and spleen while no visual effect was seen in the brain. However a histogram analysis of T1 changes in the brain demonstrated global and diffuse presence of MLNPs. The magnitude of these T1 changes scaled with post-mortem fluorescence intensity. This study demonstrates the feasibility of tracking even small amounts of magnetite labeled NPs with a sensitive histogram technique in the brain of a living rodent. PMID:24633006

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

    PubMed

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

    2014-03-15

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

  2. Effects of injected Alzheimer beta-amyloid cores in rat brain.

    PubMed Central

    Frautschy, S A; Baird, A; Cole, G M

    1991-01-01

    Although amyloid deposits have long been known to accumulate in Alzheimer disease (AD) brain, their origin and significance remain speculative. Because of the lack of an in vivo model where amyloid deposits can be induced, the relationship of the extracellular beta-amyloid deposits to other AD pathology has never been directly investigated. Therefore, we injected SDS-isolated amyloid cores into rat cortex and hippocampus. Similarly isolated lipofuscin fractions from control human brains were injected on the contralateral side. Rats were perfused and brains were examined immunohistochemically at 2 days, 7 days, and 1 month after injection. Alz-50, a monoclonal antibody against abnormally phosphorylated tau proteins, stained neurons along the cortical needle track at 2 but not 7 days after injection of either amyloid or lipofuscin. At 1 month, however, ubiquitin, Alz-50 antigen, and silver-positive structures were observed only in response to amyloid. In 7 of 10 animals, there was considerable neuronal loss in the hippocampal layers. In each instance, these effects were in the immediate vicinity of beta-protein immunoreactive material. Marked neuronal loss was never observed at any time after lipofuscin injection. These results indicate a neuronal response to amyloid. When preparations of mature plaque amyloid isolated from the AD brain are injected into the rat brain, they exert neurotoxic effects and induce antigens found in the AD brain. Images PMID:1924295

  3. Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats.

    PubMed

    Tarohda, Tohru; Ishida, Yasushi; Kawai, Keiichi; Yamamoto, Masayoshi; Amano, Ryohei

    2005-09-01

    Time courses of changes in manganese, iron, copper, and zinc concentrations were examined in regions of the brain of a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations were simultaneously determined in brain section at the level of the substantia nigra 1, 3, 7, 10, 14, and 21 days after the 6-OHDA treatment and compared with those of control rats. The distributions of these elements were obtained for 18 regions of the sagittal section (1-mm thick). The ICP-MS results indicated that Mn, Fe, Cu, and Zn levels of the 6-OHDA-induced parkinsonian brain were observed to increase in all regions that lay along the dopaminergic pathway. In the substantia nigra, the increase in Mn level occurred rapidly from 3 to 7 days and preceded those in the other elements, reaching a plateau in the 6-OHDA brain. Iron and Zn levels increased gradually until 7 days and then increased rapidly from 7 to 10 days. The increase in the copper level was slightly delayed. In other regions, such as the globus pallidus, putamen, and amygdala, the levels of Mn, Fe, Cu, and Zn increased with time after 6-OHDA treatment, although the time courses of their changes were region-specific. These findings contribute to our understanding of the roles of Mn and Fe in the induction of neurological symptoms and progressive loss of dopaminergic neurons in the development of Parkinson's disease. Manganese may hold the key to disturbing cellular Fe homeostasis and accelerating Fe levels, which play the most important role in the development of Parkinson's disease.

  4. Brain acetylcholinesterase activity in Wistar and August rats with low and high motor activity (a cytochemical study).

    PubMed

    Sergutina, A V; Rakhmanova, V I

    2014-08-01

    Acetylcholinesterase activity was quantitatively evaluated by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampus CA3 field) of August and Wistar rats demonstrating high and low motor activity in the open field test. In August rats, acetylcholinesterase activity in the analyzed brain structures prevailed in animals with high motor activity in comparison with rats with low motor activity. In Wistar rats, the differences between the animals demonstrating high and low motor activity were less pronounced, but varied depending on the experimental series of studies. Comparisons of August rats with low motor activity and Wistar rats with high motor activity (maximum difference of motor function in these animals) revealed significant excess of acetylcholinesterase activity in layer III of the sensorimotor cortex in August rats and no differences in other brain structures of the examined animals.

  5. A simple device to couple linear array transducers to neonate heads for ultrasonic scanning of the brain.

    PubMed

    Smith, W L; Franklin, T D; Katakura, K; Patrick, J T; Fry, F J; Eggleton, R C

    1980-12-01

    A plastisol coupler has been designed that improves acoustical coupling for linear array ultrasound transducers. This device improves both ease in scanning and image quality in real-time scanning of the infant brain.

  6. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    PubMed

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  7. Age-related changes in susceptibility of rat brain slice cultures including hippocampus to encephalomyocarditis virus

    PubMed Central

    Su, Weiping; Ueno-Yamanouchi, Aito; Uetsuka, Koji; Nakayama, Hiroyuki; Doi, Kunio

    1999-01-01

    Replication of the D variant of encephalomyocarditis virus (EMC-D) and its cytopathic effects were studied in the brain slice cultures including hippocampus (hippocampal slice) obtained from postnatal 1-, 4-, 7-, 14-, 28-and 56-day-old Fischer 344 rats. At 0, 12, 24, 36 and 48 h after infection, virus titres of the slices and culture media were assayed. Viral replication was observed in cultures from 1-to 28-day-old rats, and the highest titre was recorded in the slice and culture medium from the youngest rat. The peak of virus titre decreased with age and no distinct viral replication was observed in the cultures from 56-day-old rats. Light microscopy revealed that degenerative and necrotic changes appeared in the infected hippocampal slices from 1- to 28-day-old rats, and the changes became less prominent with age. In situ hybridization and indirect immunofluorescence staining showed that positive signals of viral RNA and antigen were prominent in younger rats and decreased with age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC-D is less related to the maturation of the immune system but possibly to that of the neurone. PMID:10632784

  8. A warmer ambient temperature increases the passage of interleukin-1β into the brains of old rats

    PubMed Central

    Buchanan, Jessica B.; Peloso, Elizabeth; Satinoff, Evelyn

    2008-01-01

    We have demonstrated that after intraperitoneal lipopolysaccharide (LPS) injection, old rats mount fevers similar to those of young rats at an ambient temperature (Ta) of 31°C, but not at 21°C. The same is true for intraperitoneal or intravenous IL-1β administration. The underlying mechanism responsible for blunted fever in old rats may be a deficiency in communication between the periphery and the brain. Possibly, peripheral cytokine actions are altered in old rats, such that the signal that reaches the brain is diminished. Here, we hypothesized that at standard laboratory temperatures, not enough IL-1β is reaching the brain for fever to occur and that a warmer Ta would increase the influx of IL-1β into the brain, enabling old rats to generate fever. Young (3–5 mo) and old (23–29 mo) Long-Evans rats were maintained for 3 days at either Ta 21 or 31°C prior to intravenous injection with radiolabeled IL-1β to measure passage across the blood-brain barrier. Young rats showed similar influx of IL-1β into the brain at the two Tas, but old rats showed significant influx only at the warmer Ta. These data suggest that the lack of fever at a cool Ta may be due to a reduced influx of IL-1β into the brain. PMID:18448612

  9. Fenbendazole treatment may influence lipopolysaccharide effects in rat brain.

    PubMed

    Hunter, Randy L; Choi, Dong-Young; Kincer, Jeanie F; Cass, Wayne A; Bing, Guoying; Gash, Don M

    2007-10-01

    In evaluating discrepant results between experiments in our laboratory, we collected data that challenge the notion that anthelminthic drugs like FBZ do not alter inflammatory responses. We found that FBZ significantly modulates inflammation in F344 rats intrastriatally injected with LPS. FBZ treatment of LPS-injected rats significantly increased weight loss, microglial activation, and dopamine loss; in addition, FBZ attenuated the LPS-induced loss of astrocytes. Therefore, FBZ treatment altered the effects of LPS injection. Caution should be used in interpreting data collected from rats treated with LPS and FBZ.

  10. Purification to homogeneity of an active opioid receptor from rat brain by affinity chromatography.

    PubMed

    Loukas, S; Mercouris, M; Panetsos, F; Zioudrou, C

    1994-05-10

    Active opioid binding proteins were solubilized from rat brain membranes in high yield with sodium deoxycholate in the presence of NaCl. Purification of opioid binding proteins was accomplished by opioid antagonist affinity chromatography. Chromatography using the delta-opioid antagonist N,N-diallyl-Tyr-D-Leu-Gly-Tyr-Leu attached to omega-aminododecyl-agarose (Affi-G) (procedure A) yielded a partially purified protein that binds selectively the delta-opioid agonist [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr ([3H]DSLET), with a Kd of 19 +/- 3 nM and a Bmax of 5.1 +/- 0.4 nmol/mg of protein. Subsequently, Lens culinaris agglutinin-Sepharose 4B chromatography of the Affi-G eluate resulted in isolation of an electrophoretically homogeneous protein of 58 kDa that binds selectively [3H]DSLET with a Kd of 21 +/- 3 nM and a Bmax of 16.5 +/- 1.0 nmol/mg of protein. Chromatography using the nonselective antagonist 6-aminonaloxone coupled to 6-aminohexanoic acid-Sepharose 4B (Affi-NAL) (procedure B) resulted in isolation of a protein that binds selectively [3H]DSLET with a Kd of 32 +/- 2 nM and a Bmax of 12.4 +/- 0.5 nmol/mg of protein, and NaDodSO4/PAGE revealed a major band of apparent molecular mass 58 kDa. Polyclonal antibodies (Anti-R IgG) raised against the Affi-NAL protein inhibit the specific [3H]DSLET binding to the Affi-NAL eluate and to the solubilized membranes. Moreover, the Anti-R IgG inhibits the specific binding of radiolabeled Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAMGO; mu-agonist), DSLET (delta-agonist), and naloxone to homogenates of rat brain membranes with equal potency. Furthermore, immunoaffinity chromatography of solubilized membranes resulted in the retention of a major protein of apparent molecular mass 58 kDa. In addition, immunoblotting of solubilized membranes and purified proteins from the Affi-G and Affi-NAL matrices revealed that the Anti-R IgG interacts with a protein of 58 kDa.

  11. Dynamic Multi-Coil Technique (DYNAMITE) Shimming of the Rat Brain at 11.7 Tesla

    PubMed Central

    Juchem, Christoph; Herman, Peter; Sanganahalli, Basavaraju G.; Brown, Peter B.; McIntyre, Scott; Nixon, Terence W.; Green, Dan; Hyder, Fahmeed; de Graaf, Robin A.

    2014-01-01

    The in vivo rat model is a workhorse in neuroscience research, preclinical studies and drug development. A repertoire of MR tools has been developed for its investigation, however, high levels of B0 magnetic field homogeneity are required for meaningful results. The homogenization of magnetic fields in the rat brain, i.e. shimming, is a difficult task due to a multitude of complex, susceptibility-induced field distortions. Conventional shimming with spherical harmonic (SH) functions is capable of compensating shallow field distortions in limited areas, e.g. in the cortex, but performs poorly in difficult-to-shim subcortical structures or for the entire brain. Based on the recently introduced multi-coil approach for magnetic field modeling, the DYNAmic Multi-coIl TEchnique (DYNAMITE) is introduced for magnetic field shimming of the in vivo rat brain and its benefits for gradient-echo echo-planar imaging (EPI) are demonstrated. An integrated multi-coil/radio-frequency (MC/RF) system comprising 48 individual localized DC coils for B0 shimming and a surface transceive RF coil has been developed that allows MR investigations of the anesthetized rat brain in vivo. DYNAMITE shimming with this MC/RF setup is shown to reduce the B0 standard deviation to a third of that achieved with current shim technology employing static first through third order SH shapes. The EPI signal over the rat brain increased by 31% and a 24% gain in usable EPI voxels could be realized. DYNAMITE shimming is expected to critically benefit a wide range of preclinical and neuroscientific MR research. Improved magnetic field homogeneity, along with the achievable large brain coverage of this method will be crucial when signal pathways, cortical circuitry or the brain’s default network are studied. Along with the efficiency gains of MC-based shimming compared to SH approaches demonstrated recently, DYNAMITE shimming has the potential to replace conventional SH shim systems in small bore animal

  12. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    SciTech Connect

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  13. Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

    PubMed Central

    Geldof, Marian; Freijer, Jan; van Beijsterveldt, Ludy

    2007-01-01

    Introduction A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg−1 of fluvoxamine. Analysis With increasing dose a disproportional increase in brain concentrations was observed. The kinetics of brain distribution was estimated by simultaneous analysis of plasma, free brain ECF and total brain tissue concentrations. The PK model consists of three compartments for fluvoxamine concentrations in plasma in combination with a catenary two compartment model for distribution into the brain. In this catenary model, the mass exchange between a shallow perfusion-limited and a deep brain compartment is described by a passive diffusion term and a saturable active efflux term. Results The model resulted in precise estimates of the parameters describing passive influx into (kin) of 0.16 min−1 and efflux from the shallow brain compartment (kout) of 0.019 min−1 and the fluvoxamine concentration at which 50% of the maximum active efflux (C50) is reached of 710 ng.ml−1. The proposed brain distribution model constitutes a basis for precise characterization of the PK–PD correlation of fluvoxamine by taking into account the non-linearity in brain distribution. PMID:17710515

  14. Evidence for a presynaptic adenylate cyclase system facilitating (TH)norepinephrine release from rat brain neocortex slices and synaptosomes

    SciTech Connect

    Schoffelmeer, A.N.; Hogenboom, F.; Mulder, A.H.

    1985-10-01

    The effects of drugs known to enhance intracellular cyclic AMP levels on depolarization-induced (TH)norepinephrine release from superfused rat neocortical slices and synaptosomes were investigated. The adenylate cyclase activator forskolin, the membrane-permeating cyclic AMP analogues 8-bromo-cyclic AMP and dibutyryl cyclic AMP, as well as the phosphodiesterase inhibitors isobutylmethylxanthine and 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrolidone (ZK 62771) enhanced the electrically evoked release of (TH)norepinephrine from superfused rat brain neocortex slices. 8-Bromo-cyclic GMP was without effect on the electrically evoked release. When (TH)norepinephrine release was enhanced by prolonging the electrical pulse duration from 2 msec to 10 msec, the relative inhibitory effect of the CaS channel blocker CdS and the relative facilitatory effect of the K+ channel blocker 4-aminopyridine remained unaffected. In striking contrast, the relative facilitatory effects of forskolin and 8-bromo-cyclic AMP were strongly reduced, whereas the effect of ZK 62771 was almost doubled. When veratrine-induced release of (TH)norepinephrine from cortex synaptosomes was examined, the facilitatory effects of forskolin, 8-bromo-cyclic AMP, and ZK 62771 were even more pronounced than in brain slices. The data strongly support the hypothesis that a presynaptic adenylate cyclase system plays a facilitatory role in the stimulus-secretion coupling process in central noradrenergic nerve terminals.

  15. Conditioned feeding suppression in rats produced by cross-coupled and simple motions

    NASA Technical Reports Server (NTRS)

    Fox, R. A.; Daunton, N. G.

    1982-01-01

    Results are presented of an experiment on the induction of motion sickness in rats by the use of cross-coupled accelerations of magnitudes similar to those used in human experiments. Accelerations were produced in a seesaw apparatus with rotating disks supporting the animal cages mounted on each seesaw arm, and motion sickness was assessed according to the consumption of a sweet food previously offered to the animals immediately before the motion treatment. During a 1-hour test session 72 h after motion treatment and after a 24-h fast, rats having undergone cross-coupled vertical sinusoidal and rotational motion are observed to consume less food than those having experienced either type of motion alone, or no motion. The ordering of the conditioned suppressive feeding effects is consistent with the amounts of vestibular stimulation produced by the respective motions. The results support the existence of motion sickness effects in rats, even though they are unable to vomit.

  16. Dietary cholesterol and the origin of cholesterol in the brain of developing rats.

    PubMed

    Edmond, J; Korsak, R A; Morrow, J W; Torok-Both, G; Catlin, D H

    1991-09-01

    Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires.

  17. Mössbauer and X-ray study of biodegradation of 57Fe3 O 4 magnetic nanoparticles in rat brain

    NASA Astrophysics Data System (ADS)

    Gabbasov, R. R.; Cherepanov, V. M.; Chuev, M. A.; Lomov, A. A.; Mischenko, I. N.; Nikitin, M. P.; Polikarpov, M. A.; Panchenko, V. Y.

    2016-12-01

    Biodegradation of a 57Fe3 O 4 - based dextran - stabilized ferrofluid in the ventricular cavities of the rat brain was studied by X-ray diffraction and Mössbauer spectroscopy. A two-step process of biodegradation, consisting of fast disintegration of the initial composite magnetic beads into separate superparamagnetic nanoparticles and subsequent slow dissolution of the nanoparticles has been found. Joint fitting of the couples of Mössbauer spectra measured at different temperatures in the formalism of multi-level relaxation model with one set of fitting parameters, allowed us to measure concentration of exogenous iron in the rat brain as a function of time after the injection of nanoparticles.

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

    PubMed Central

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

    2016-01-01

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

  19. Atrial natriuretic peptide in the rat brain and plasma during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1994-01-01

    By means of the radioimmunologic method changes of ANP content in the rat brain and plasma have been evaluated during 5-min clinical death and up to 2 hr after resuscitation. Ischemia did not produce significant rise of ANP immunoreactivity in the brain, however, in the early postresuscitation period its reversible increase was noted with the peak value at 15th min. The content of peptide in plasma significantly increased at the end of clinical death and 5 min after resuscitation. The obtained results can support the notion of quantitative relationship between concentration of ANP and cGMP content in the brain in vivo.

  20. An opiate binding site in the rat brain is highly selective for 4,5-epoxymorphinans.

    PubMed

    Grevel, J; Sadée, W

    1983-09-16

    In vitro binding studies have demonstrated the existence of multiple opiate receptor types. An additional site in the rat brain (termed the lambda site) is distinct from the established types by its selectivity for 4,5-epoxymorphinans (such as naloxone and morphine). While the lambda site displays a high affinity for naloxone in vivo and in vitro in fresh brain membrane homogenates, these sites rapidly convert in vitro to a state of low affinity. The regional distribution of the lambda site in the brain is strikingly different from that of the classic opiate receptor types.

  1. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    SciTech Connect

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  2. Dopamine release in rat striatum - Physiological coupling to tyrosine supply

    NASA Technical Reports Server (NTRS)

    During, Matthew J.; Acworth, Ian N.; Wurtman, Richard J.

    1989-01-01

    Intracerebral microdialysis was used to monitor dopamine release in rat striatal extracellular fluid following the intraperitoneal administration of dopamine's precursor amino acid, L-tyrosine. Dopamine concentrations in dialysates increased transiently after tyrosine (50-100 mg/kg) administration. Pretreatment with haloperidol or the partial lesioning of nigrostriatal neurons enhanced the effect of tyrosine on dopamine release, and haloperidol also prolonged this effect. These data suggest that nigrostriatal dopaminergic neurons are responsive to changes in precursor availability under basal conditions, but that receptor-mediated feedback mechanisms limit the magnitude and duration of this effect.

  3. 65zinc uptake from blood into brain and other tissues in the rat

    SciTech Connect

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. )

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  4. Clearance of Gadolinium from the Brain with No Pathologic Effect after Repeated Administration of Gadodiamide in Healthy Rats: An Analytical and Histologic Study.

    PubMed

    Smith, Adrian P L; Marino, Michael; Roberts, Jeanette; Crowder, Janell M; Castle, Jason; Lowery, Lisa; Morton, Christine; Hibberd, Mark G; Evans, Paul M

    2017-03-01

    Purpose To measure the levels of gadolinium present in the rat brain 1 and 20 weeks after dosing with contrast agent and to determine if there are any histopathologic sequelae. Materials and Methods The study was approved by the GE Global Research Center Institutional Animal Care and Use Committee. Absolute gadolinium levels were quantified in the blood and brains of rats 1 week after dosing and 20 weeks after dosing with up to 20 repeat doses of gadodiamide (cumulative dose, 12 mmol per kilogram of body weight) by using inductively coupled plasma-mass spectrometry. Treatment groups (n = 6 rats per group) included low-dosage and high-dosage gadodiamide and osmolality-matched saline controls. Brain sections were submitted (blinded) for standard toxicology assessment per Registry of Industrial Toxicology Animal data guidelines. Analysis of variance and Mann-Whitney U tests with post hoc correction were used to assess differences in absolute gadolinium levels and percentage of injected dose, respectively. Results Dose-dependent low levels of gadolinium were detected in the brain, a mean ± standard deviation of 2.49 nmol per gram of brain tissue ± 0.30 or 0.00019% of the injected dose 1 week after dosing. This diminished by approximately 50% (to 1.38 nmol per gram of brain tissue ± 0.10 or 0.00011% of the injected dose) 20 weeks after dosing. As a percentage of injected dose, the levels of gadolinium measured were comparable between different doses, indicating that mechanisms of uptake and elimination were not saturated at the tested doses. There were no histopathologic findings associated with the levels of gadolinium measured. Conclusion Low levels of gadolinium are present in the brain after repeat dosing with gadodiamide, which is partially cleared over 20 weeks with no detectable neurotoxicity.

  5. The primary structure of rat brain (cytoplasmic) dynein heavy chain, a cytoplasmic motor enzyme.

    PubMed Central

    Zhang, Z; Tanaka, Y; Nonaka, S; Aizawa, H; Kawasaki, H; Nakata, T; Hirokawa, N

    1993-01-01

    Overlapping cDNA clones encoding the heavy chain of rat brain cytoplasmic dynein have been isolated. The isolated cDNA clones contain an open reading frame of 13,932 bp encoding 4644 aa (M(r), 532,213). The deduced protein sequence of the heavy chain of rat brain dynein shows significant similarity to sea urchin flagellar beta-dynein (27.0% identical) and to Dictyostelium cytoplasmic dynein (53.5% identical) throughout the entire sequence. The heavy chain of rat brain (cytoplasmic) dynein contains four putative nucleotide-binding consensus sequences [GX4GK(T/S)] in the central one-third region that are highly similar to those of sea urchin and Dictyostelium dyneins. The N-terminal one-third of the heavy chain of rat brain (cytoplasmic) dynein shows high similarity (43.8% identical) to that of Dictyostelium cytoplasmic dynein but poor similarity (19.4% identical) to that of sea urchin flagellar dynein. These results suggested that the C-terminal two-thirds of the dynein molecule is conserved and plays an essential role in microtubule-dependent motility activity, whereas the N-terminal regions are different between cytoplasmic and flagellar dyneins. Images Fig. 1 PMID:7690137

  6. The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

    EPA Science Inventory

    The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

  7. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  8. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    PubMed

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  9. Effects of dexamethasone on aquaporin-4 expression in brain tissue of rat with bacterial meningitis

    PubMed Central

    Du, Kai-Xian; Dong, Yan; Zhang, Yan; Hou, Li-Wei; Fan, Dong-Xia; Luo, Yu; Zhang, Xiao-Li; Jia, Tian-Ming; Lou, Ji-Yu

    2015-01-01

    Aquaporin-4 (AQP4) is the most popular water channel protein expressed in brain tissue and plays a very important role in regulating the water balance in and outside of brain parenchyma. To investigate the expression of aquaporin-4 in the rat brain tissue after dexamethasone therapy of meningitis induced by Streptococcus pneumonia, total 40 of 3-week old Sprague-Dawley rats were divided into infection group (n=30) and normal control group (n=10). The meningitis groups were infected with 1×107 cfu/ml of Streptococcus pneumoniae and then randomized into no treatment (untreated group, n=10), treatment with ceftriaxone (CTRX group, n=10) and treatment with dexamethasone combined ceftriaxone (CTRX + DEXA group, n=10). The normal control group was established by using saline. The rats were euthanized when they reached terminal illness or five days after infection, followed by detection of AQP4 through using immunohistochemistry and Western blot methods. Data has showed that expression of AQP4 in model group remained higher than the control and treatment group (P<0.05). AQP4 expression in CTRX + DEXA group was lower than that in CTRX group (P<0.05). There was no statistical difference between CTRX + DEXA group and the control group (P>0.05). These data suggested that Dexamethasone could down-regulate the expression of AQP4 in the brain tissue of rats with meningitis and provides evidence for the mechanism of protective effect of Dexamethasone on central neurosystem. PMID:26045822

  10. Effects of ageing on the content in sulfur-containing amino acids in rat brain.

    PubMed

    Benedetti, M S; Russo, A; Marrari, P; Dostert, P

    1991-01-01

    Concentrations of the sulfur-containing amino acids methionine, homocysteic acid, cysteic acid and taurine were measured in brain structures of young and old Wistar rats in an attempt to establish a possible link between the increase in oxidative stress with ageing and changes in tissue levels of these amino acids. Contrary to data reported by others, in all brain structures of young and old rats homocysteic acid levels could not be quantified. Compared with young rats, in old animals taurine and methionine concentrations significantly decreased in striatum and cortex; decreased taurine levels were also found in nucleus accumbens and cerebellum and lower concentrations of methionine were found in midbrain, hippocampus and pons-medulla. Cysteic acid levels either did not change or significantly increased in cortex and hippocampus. These results are discussed taking into account the biosynthesis of sulfur-containing amino acids in rat brain and the decrease in glutathione in relation to oxidative stress with ageing. Changes in aspartic acid, glutamic acid, serine, glutamine, glycine and GABA concentrations with ageing were also determined in the same brain structures and were in good agreement with those previously reported (Strolin Benedetti et al., 1990 a, b).

  11. Increased folate uptake prevents dietary development of folate deficiency in the rat brain

    SciTech Connect

    McMartin, K.E.; Collins, T.D.; Eisenga, B.H.; Bhandari, S.D. )

    1990-02-26

    Folic acid and folate deficiency have been implicated in disorders of the central nervous system. In a study of the mechanism for the effects of chronic ethanol on folate homeostasis, the uptake of {sup 3}H-folic acid by the rat brain has been studied. Male Sprague-Dawley rats were fed sulfonamide-supplemented folate-sufficient and folate-deficient liquid diets containing either ethanol or isoenergic carbohydrate as a control. After 16 weeks, severe folate depletion occurred in tissues (liver, kidney, spleen, lung intestine, testes), but not in the brain. Tissue retention of {sup 3}H-folic acid was increased four-fold in the brain of folate-deficient rats. A smaller increase in uptake was observed in the other tissues, except for the liver, in which the retention of {sup 3}H-folic acid was slightly decreased. Chronic ethanol feeding decreased hepatic folate uptake, but not that by the increase the uptake of folate from the plasma of folate-deficient rats, thereby inhibiting the development of brain folate deficiency.

  12. Cloning and expression of Ca2+-activated chloride channel from rat brain.

    PubMed

    Jeong, Sang Min; Park, Hye-Kyung; Yoon, In-Soo; Lee, Jun-Ho; Kim, Jong-Hoon; Jang, Choon-Gon; Lee, C Justin; Nah, Seung-Yeol

    2005-08-26

    To clone the gene product responsible for the calcium-activated chloride channel (CLCA) in rat brain cerebrum, we performed a reverse transcription-PCR (RT-PCR) with gene-specific primers of a rat EST clone. We successfully cloned a rat brain CLCA (rbCLCA). The full-length cDNA is 2895 bp long and codes for a 902 amino acid protein. The clone consists of four transmembrane domains and shows a 79.1% of significant homology with previously reported mouse smooth muscle chloride channel sequence. We also performed RT-PCR using single neuron and glia, and various tissues to determine the tissue expression of rbCLCA. We found that rbCLCA was expressed in both neuron and glia. In peripheral organs, rbCLCA showed the predominant expressions in cerebrum, cerebellum, kidney, small intestine, and stomach but not in heart, large intestine, liver, lung, and spleen. Whole-cell patch clamp studies in HEK293 cells transfected with the clone identified a niflumic acid (a CLCA channel blocker)-sensitive and voltage-dependent chloride current but we could not observe this chloride current in mock-transfected cells. The identification of genes belonging to the CLCA family from rat brain and its functional expression will help to evaluate its physiological role in brain as anion channel.

  13. Stability of Rat Brain Glutamine Synthetase to Oxygen Toxicity (Oxygen at High Pressure).

    DTIC Science & Technology

    1983-07-01

    Enzyme assays using the gamma-glutamyl transferase method provided estimates of glutamine synthetase activity in rat brain homogenates subjected to a...supports the lack of any connection between convulsions caused by in vivo inhibition of glutamine synthetase and convulsions caused by oxygen toxicity (oxygen at high pressure). (Author)

  14. Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

    SciTech Connect

    Maeepea, O.; Karlsson, C.; Alm, A.

    1984-09-01

    Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers.

  15. Antidiabetic and neuroprotective effects of Trigonella foenum-graecum seed powder in diabetic rat brain.

    PubMed

    Kumar, P; Kale, R K; McLean, P; Baquer, N Z

    2012-01-01

    Trigonella foenum-graecum seed powder (TSP) has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase, glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hyperglycemia on alterations in lipid peroxidation, restoring membrane fluidity, activities of membrane bound and antioxidant enzymes, thereby ameliorating the diabetic complications.

  16. THYROID INSUFFICIENCY AND GENE EXPRESSION IN DEVELOPING RAT BRAIN: A DOSE RESPONSE STUDY.

    EPA Science Inventory

    Thyroid Insufficiency and Gene Expression in Developing Rat Brain: A Dose Response Study. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption is an area of major concern in environmental neurotoxicity. Deficits in thyroid hormone (TH) levels h...

  17. PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

    EPA Science Inventory

    In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

  18. Validation of the quantification of histamine in rat brain using the radioenzymatic assay

    SciTech Connect

    Russell, W.L.; Henry, D.P.

    1986-03-01

    Quantification of histamine (Hm) in rat brain is problematic. The authors have evaluated tissue extraction procedures and validated a new Hm radioenzymatic assay for brain. Brain was extracted twice with either 0.1M perchloric acid (PCA), boiling water, or water. Sacrifice by microwave irradiation increased whole brain Hm from 64.4 +/- 16.5 to 450.9 +/- 90.8 ng/g. The validity of the assay was demonstrated by isolating the product formed by the radioenzymatic assay and subjecting it to TLC and autoradiography. The sensitivity of this assay permitted the quantification of Hm in as little as 4.3 ..mu..g of hypothalamus. The authors conclude: 1) The preferred method for sacrifice is decapitation; 2) homogenization in PCA effectively extracts Hm from brain tissue; 3) the radioenzymatic assay is specific for Hm in this tissue.

  19. Effect of clinical death on inositol 1,4,5-trisphosphate in the rat brain.

    PubMed

    Kapuściński, A

    1993-01-01

    Changes of inositol 1,4,5-trisphosphate content in the rat brain have been evaluated by means of the radioimmunologic method during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia produced a decrease of IP3 content in the brain on the average to 63% of the control values. IP3 concentration in the brain increased on the average to 197% of the control values at the 15th min after resuscitation, and decreased to 127% at the 60 min. Two hours after resuscitation the IP3 content in the brain again increased on the average to 187%. The new data on brain metabolism in the ischemic conditions and the role of IP3 as the second messenger and mediator of neuromodulation processes are discussed.

  20. Evaluation of fluoride-induced oxidative stress in rat brain: a multigeneration study.

    PubMed

    Basha, P Mahaboob; Rai, Puja; Begum, Shabana

    2011-09-01

    Multigenerational evaluation was made in rats on exposure to high fluoride (100 and 200 ppm) to assess neurotoxic potential of fluoride in discrete areas of the brain in terms of lipid peroxidation and the activity of antioxidant enzyme system. The rats were given fluoride through drinking water (100 and 200 ppm) and maintained subsequently for three generations. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes viz, catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione level in first-generation rats and these alterations were more pronounced in the subsequent second and third-generation rats in both the doses tested. Decreased feed and water consumption, litter size and organ (brain) somatic index, marginal drop in body growth rate and mortality were observed in all three generations. Decreased antioxidant enzyme activity and increased malondialdehyde levels found in the present study might be related to oxidative damage that occurs variably in discrete regions of the brain. Results of this study can be taken as an index of neurotoxicity in rats exposed to water fluoridation over several generations.

  1. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  2. Reference memory and allocentric spatial localization deficits after unilateral cortical brain injury in the rat.

    PubMed

    Soblosky, J S; Tabor, S L; Matthews, M A; Davidson, J F; Chorney, D A; Carey, M E

    1996-10-01

    Traumatic brain injury (TBI) produces learning and memory impairments in humans. This study investigated the effects of TBI on memory and spatial localization strategies in rats. Prior to TBI, separate groups of rats were trained in an 8-arm radial maze with either all 8 arms baited (Expt. 1) or only 4 of the 8 arms baited (Expt. 2). TBI was produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Rats used in Expt. 1 were selected because they did not use a stereotypic response strategy (going to adjacent arms) in performing the maze before injury. After TBI the rats were not different from control rats in the number of working memory (WM) errors made. They did, however, display a distinct propensity to go to adjacent arms, i.e., exhibit stereotypic behavior, with a right-handed (ipsiversive) bias (P < 0.005). After TBI, rats which were trained with only 4 of 8 arms baited committed more reference memory (RM) errors than control rats (P < 0.05). They did not differ from controls on WM errors. Injured rats took longer to re-attain criteria than controls (P < 0.0001). Injured rats also initially displayed a propensity to enter the adjacent arm sequentially before re-attaining criteria. Further analysis indicated that injured rats re-learned the maze with a right-hand bias (P < 0.0001). The results of both experiments suggest that after TBI, rats shifted from an allocentric to an egocentric strategy to re-learn the maze. It was suggested that damage to the parietal cortex may have been responsible for both RM errors and the shift away from an allocentric strategy to an egocentric strategy. Possibly, the ipsiversive (right-hand) bias may be the result of a behaviorally or injury-induced neurochemical asymmetry within the motor system.

  3. Irradiation of rat brain reduces P-glycoprotein expression and function.

    PubMed

    Bart, J; Nagengast, W B; Coppes, R P; Wegman, T D; van der Graaf, W T A; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N H

    2007-08-06

    The blood-brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats were irradiated with single doses of 2-25 Gy followed by 10 mg kg(-1) of the P-gp substrate cyclosporine A (CsA) intravenously (i.v.), with once 15 Gy followed by CsA (10, 15 or 20 mg kg(-1)), or with fractionated irradiation (4 x 5 Gy) followed by CsA (10 mg kg(-1)) 5 days later. Additionally, four groups of three rats received 25 Gy once and were killed 10, 15, 20 or 25 days later. The brains were removed and P-gp detected immunohistochemically. P-gp function was assessed by [(11)C]carvedilol uptake using quantitative autoradiography. Irradiation increased [(11)C]carvedilol uptake dose-dependently, to a maximum of 20% above non irradiated hemisphere. CsA increased [(11)C]carvedilol uptake dose-dependently in both hemispheres, but more (P<0.001) in the irradiated hemisphere. Fractionated irradiation resulted in a lost P-gp expression 10 days after start irradiation, which coincided with increased [(11)C]carvedilol uptake. P-gp expression decreased between day 15 and 20 after single dose irradiation, and increased again thereafter. Rat brain irradiation results in a temporary decreased P-gp function.

  4. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  5. Developmental Expression of Orphan G Protein-Coupled Receptor 50 in the Mouse Brain

    PubMed Central

    2012-01-01

    Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a specific function has not been identified. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identified novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis. PMID:22860215

  6. Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

    SciTech Connect

    Mendelsohn, L.G.; Kerchner, G.A.; Clemens, J.A.; Smith, M.C.

    1986-03-01

    The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human /sup 125/-I-IGF-II (10 pM) was incubated for 16 hrs at 4/sup 0/C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA/sub 1/-CA/sub 2/ and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of /sup 125/I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning.

  7. Behavioral changes and brain energy metabolism dysfunction in rats treated with methamphetamine or dextroamphetamine.

    PubMed

    Feier, Gustavo; Valvassori, Samira S; Lopes-Borges, Jéssica; Varela, Roger B; Bavaresco, Daniela V; Scaini, Giselli; Morais, Meline O; Andersen, Monica L; Streck, Emilio L; Quevedo, João

    2012-11-14

    Studies have demonstrated that AMPHs produce long-term damage to the brain dopaminergic, serotoninergic and glutamatergic regions. Prefrontal cortex, amygdala, hippocampus and striatum appear to be involved in the toxicity and behavioral changes induced by AMPHs. A single dose of AMPH causes mitochondrial dysfunction and oxidative stress in rat brain. The goal of the present study was thus to investigate the potency of two amphetamines, dextroamphetamine (d-AMPH) and methamphetamine (m-AMPH), on the behavior and energetic dysfunction in the brain of rats. d-AMPH and m-AMPH increased the crossing and rearing behaviors. The numbers of visits to the center were increased by d-AMPH and m-AMPH only at 2mg/kg. Likewise, at a high dose (2 mg/kg), the injection of m-AMPH increased the amount of sniffing. The AMPHs significantly decreased the activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase) and mitochondrial respiratory chain complexes (I-IV); nevertheless, this effect varied depending on the brain region evaluated. In summary, this study demonstrated that at high doses, m-AMPH, increased stereotyped (sniffing) behavior in rats, but d-AMPH did not. However, this study shows that d-AMPH and m-AMPH seem to have similar effects on the brains energetic metabolism.

  8. Effect of 900 MHz radiofrequency radiation on oxidative stress in rat brain and serum.

    PubMed

    Bilgici, Birsen; Akar, Aysegul; Avci, Bahattin; Tuncel, Ozgur Korhan

    2013-03-01

    The increasing use of mobile telephones raises the question of possible adverse effects of the electromagnetic fields (EMF) that these phones produce. In this study, we examined the oxidative stress in the brain tissue and serum of rats that resulted from exposure to a 900-MHz EMF at a whole body average specific absorption rate (SAR) of 1.08 W/kg for 1 h/day for 3 weeks. We also examined the antioxidant effect of garlic powder (500 mg/kg/day) given orally to EMF-exposed rats. We found that malondialdehyde (MDA) (p < 0.001) and advanced oxidation protein product (AOPP) (p < 0.05) increased in rat brain tissue exposed to the EMF and that garlic reduced these effects (p < 0.05). There was no significant difference in the nitric oxide (NO) levels in the brain. Paraoxonase (PON) was not detected in the brain. There was a significant increase in the levels of NO (p < 0.001) detected in the serum after EMF exposure, and garlic intake did not affect this increase in NO. Our results suggest that there is a significant increase in brain lipid and protein oxidation after electromagnetic radiation (EMR) exposure and that garlic has a protective effect against this oxidative stress.

  9. Interaction of ethanol and microwaves on the blood-brain barrier of rats

    SciTech Connect

    Neilly, J.P.; Lin, J.C.

    1986-01-01

    The combined effects of ethanol and microwaves on the permeation of Evans blue dye through the mammalian blood-brain barrier was studied in male Wistar rats. Anesthetized rats were infused through a cannula in the left femoral vein with 0.1, 0.3, 0.5 or 0.7 grams of absolute ethanol per kilogram of body mass. A control group was given 0.7 g/kg of isotonic saline. The left hemisphere of the brain was irradiated by 3.15-GHz microwave energy at 3.0 W/cm2 rms for 15 min. The rat's rectal temperature was maintained at 37.0 degrees C. Immediately after irradiation, 2% Evans blue dye in saline (2.0 ml/kg body mass) was injected through the cannula. The results show that as the quantity of alcohol was increased, the degree of staining was decreased or eliminated. The temperature of the irradiated area of the brain increased for the first 4 to 5 minutes of irradiation and then stabilized for the remainder of the irradiation period. The steady-state temperature was highest in animals receiving saline or the smallest dose of alcohol. As the quantity of alcohol was increased, the steady-state temperature was reduced. These results indicate that ethanol inhibits microwave-induced permeation of the blood-brain barrier through reduced heating of the brain.

  10. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups.

    PubMed

    Yazdani, Armin; Khoja, Zehra; Johnstone, Aaron; Dale, Laura; Rampakakis, Emmanouil; Wintermark, Pia

    2016-01-01

    Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

  11. DIETARY N-6 POLYUNSATURATED FATTY ACID DEPRIVATION INCREASES DOCOSAHEXAENOIC ACID METABOLISM IN RAT BRAIN

    PubMed Central

    Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.

    2011-01-01

    Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A2 (cPLA2-IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective Ca2+-independent iPLA2-VIA expression. We hypothesized that these changes are accompanied by upregulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA “adequate” (31.4 wt% linoleic acid) or “deficient” (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-14C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acidn-3 (DPAn-3, 22:5n-3) and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid. Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promote neuroprotection. (199 words) PMID:22117540

  12. Uptake and biodistribution of rizatriptan to blood and brain following different routes of administration in rats.

    PubMed

    Wang, Chun; Quan, Li-Hui; Guo, Yi; Liu, Chun-Yu; Liao, Yong-Hong

    2007-06-07

    The objective of the present study was to investigate the biodistribution profiles of rizatriptan in the blood and brain of Wistar rats after peroral, subcutaneous, intranasal and intratracheal administration with a particular view to determining the applicability of inhalation delivery to achieve rapid and high availability of the drug in both blood and the brain. Following the intratracheal administration of the drug (4.0mg/kg) to the rats, the absolute bioavailability was found to be 91.2%, significantly higher than those from intranasal or peroral routes, and T(max) in plasma and brain was attained within 2 min, significantly shorter than the T(max) of intranasal ( approximately 10 min in both plasma and brain), subcutaneous (16.7 min in plasma and 22.5 min in brain) and peroral (30.0 min in plasma and 45.0 min in brain) administration. In addition, other pharmacokinetic parameters associated with rapid onset of action including AUC(plasma/brain) and C(max), of intratracheal instillated rizatriptan appeared also to be comparable or superior to those of other delivered routes. Although AUC(brain)/AUC(plasma) ratios after intranasal delivery (43.4%) differed significantly from the ratios shown after intratracheal instillation (23.2%), the AUC(brain 0-120 min) via the latter routes was slightly but not significantly higher than that from the former routes. The results in the present study indicated that pulmonary delivery of rizatriptan may achieve maximum plasma and brain concentrations significantly more rapidly compared with intranasal, subcutaneous and peroral administration and be a promising delivery method with extremely rapid onset of action in the pain relief of migraine.

  13. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  14. Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Paweł; Wierzba-Bobrowicz, Teresa; Majewska, Maria D

    2010-01-01

    Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.

  15. [Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration].

    PubMed

    Shevchenko, K V; Nagaev, I Iu; Alfeeva, L Iu; Andreeva, L A; Kamenskiĭ, A A; Levitskaia, N G; Shevchenko, V P; Grivennikov, I A; Miasoedov, N F

    2006-01-01

    The radioactive peptide analogue Semax corresponding to the ACTH(4-10) sequence (Met-Glu-His-Phe-Pro-Gly-Pro) with a molar radioactivity of 56 Ci/mmol labeled with tritium at the C-terminal Pro was prepared. The labeled peptide was used for studying the kinetics of Semax penetration into rat brain and blood after its intranasal administration (50 microg/kg, 20 microl of solution) to nonbred white rats of body mass 200-250 g. It was demonstrated that 0.093% of the total introduced radioactivity per gram can be found in the rat brain 2 min after the administration, 80% of this radioactivity belonged to Semax, and the rest, to its metabolites. The peptide undergoes rapid enzymatic degradation, with the tripeptide Pro-Gly-Pro prevailing in biological samples relative to the total content of Semax and its metabolites.

  16. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects.

  17. Brain of rats intoxicated with acrylamide: observation with 4.7 tesla magnetic resonance.

    PubMed

    Kinoshita, Y; Matsumura, H; Igisu, H; Yokota, A

    2000-10-01

    When rats were injected intraperitoneally with acrylamide (50 mg/kg per day) for 8 days, all animals developed ataxia and weakness in the hindlimbs. On examining their brain with an ultrahigh-field (4.7 T) magnetic resonance (MR) spectrometer, the lateral ventricles on both sides and the third ventricle were dilated. The aqueduct and cisterns were also enlarged. The size of the cerebral cortex was quantified in three MR image slices covering the cerebrum. Compared with the images of the brain of body weight-matched controls, the cerebral cortex of rats intoxicated with acrylamide was found to be smaller in the primary motor area in all slices, and in the primary or secondary sensory area in two slices. Taken together with previous enzymatic analyses, rats intoxicated with acrylamide (50 mg/kg per day for 8 days) seem to represent an animal model of acrylamide encephalopathy not only biochemically but also structurally.

  18. Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress.

    PubMed

    Pintana, Hiranya; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-10-01

    Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats.

  19. Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats

    PubMed Central

    Casquero-Veiga, Marta; Hadar, Ravit; Pascau, Javier; Winter, Christine; Desco, Manuel; Soto-Montenegro, María Luisa

    2016-01-01

    Objective To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats. Methods 43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping. Results DBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex. Conclusions DBS induced significant changes in 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FDG uptake despite interacting with the same circuitries. This may have important implications to DBS research suggesting individualized target selection according to specific neural modulatory requirements. PMID:28033356

  20. Brain and body temperature homeostasis during sodium pentobarbital anesthesia with and without body warming in rats.

    PubMed

    Kiyatkin, Eugene A; Brown, P Leon

    2005-03-31

    High-speed, multi-site thermorecording offers the ability to follow the dynamics of heat production and flow in an organism. This approach was used to study brain-body temperature homeostasis during the development of general anesthesia induced by sodium pentobarbital (50 mg/kg, ip) in rats. Animals were chronically implanted with thermocouple probes in two brain areas, the abdominal cavity, and subcutaneously, and temperatures were measured during anesthesia both with and without (control) body warming. In control conditions, temperature in all sites rapidly and strongly decreased (from 36-37 degrees C to 32-33 degrees C, or 3.5-4.5 degrees C below baselines). Relative to body core, brain hypothermia was greater (by 0.3-0.4 degrees C) and skin hypothermia was less (by approximately 0.7 degrees C). If the body was kept warm with a heating pad, brain hypothermia was three-fold weaker ( approximately 1.2 degrees C), but the brain-body difference was significantly augmented (-0.6 degrees C). These results suggest that pentobarbital-induced inhibition of brain metabolic activity is a major factor behind brain hypothermia and global body hypothermia during general anesthesia. These data also indicate that body warming is unable to fully compensate for anesthesia-induced brain hypothermia and enhances the negative brain-body temperature differentials typical of anesthesia. Since temperature strongly affects various underlying parameters of neuronal activity, these findings are important for electrophysiological studies performed in anesthetized animal preparations.

  1. Inhibition of rat brain monoamine oxidase by repeated administration of pirlindol

    SciTech Connect

    Verevkina, I.V.; Asnina, V.V.; Gorkin, V.Z.; Mashovskii, M.D.

    1985-10-01

    Since pirlindol, like other antidepressants, is used for a long time and since its therapeutic effect usually appears 5-7 days or more after the beginning of treatment, the authors investigate its action on activity of MAO of types A and B in rat brain when administered repeatedly. MAO activity was determined in 50% homogenates of rat brain, made up in 10 mM phosphate buffer, pH 7.4, containing 2% detergent Triton X-100. It is shown that an important role in the antidepressant effect of pirlindol is played by its property of selectively blocking deamination of neurotrans mitters such as serotonin and noradrenalin in the human brain.

  2. Central alpha 1- and alpha 2-adrenoceptors and brain cholinergic stimulation in sinoaortic denervated rats.

    PubMed

    Taira, C A; Enero, M A

    1994-12-12

    The central alpha-adrenoceptor role in cardiovascular responses to intracerebroventricular (i.c.v.) injection of neostigmine, a tertiary anticholinesterase, was studied in conscious sham-operated and sinoaortic-denervated rats. Neostigmine (0.1-1 micrograms i.c.v.) showed dose-dependent pressor and bradycardiac effects in vehicle-pretreated sham-operated rats but only an increased pressor effect in sinoaortic-denervated animals. The pretreatment with the catecholaminergic neurotoxin, 6-hydroxydopamine (250 micrograms i.c.v.), given 72 h previous to the corresponding operation, blunted the cardiovascular effects of neostigmine in both groups of rats. Prazosin (10 and 30 micrograms i.c.v.), an alpha 1-adrenoceptor antagonist, prevented the pressor response to neostigmine (0.3 micrograms i.c.v.) in sham-operated and sinoaortic-denervated rats. Yohimbine, a alpha 2-adrenoceptor antagonist (10 and 30 micrograms i.c.v.), only prevented the bradycardia induced by neostigmine (0.3 micrograms i.c.v.) in the sham-operated rats. 6-Hydroxydopamine pretreatment lowered the norepinephrine content in hypothalamus, midbrain, medulla oblongata and spinal cord, but did not modify it in the pons, in sham-operated rats and sinoaortic-denervated animals. The present results suggested that brain alpha 1-adrenoceptors would mediate the pressor response to neostigmine (i.c.v.) in sham-operated and sinoaortic-denervated rats and central alpha 2-adrenoceptors mediate the bradycardia in sham-operated rats. This work lends support to the view that cardiovascular responses to brain cholinergic stimulation in sham-operated and sinoaortic-denervated rats could be mediated by a central catecholaminergic activation.

  3. Hyperglycolysis is exacerbated after traumatic brain injury with fentanyl vs. isoflurane anesthesia in rats.

    PubMed

    Statler, Kimberly D; Janesko, Keri L; Melick, John A; Clark, Robert S B; Jenkins, Larry W; Kochanek, Patrick M

    2003-12-19

    Despite common use of narcotics in the clinical management of severe traumatic brain injury (TBI), in experimental models rats treated with fentanyl have exhibited worse functional outcome and more CA1 hippocampal death than rats treated with standard isoflurane anesthesia. We hypothesized that greater post-traumatic excitotoxicity, reflected by cerebral glucose utilization (CMRglu), may account for detrimental effects of fentanyl vs. isoflurane. Rats were anesthetized with either isoflurane (1% by inhalation) or fentanyl (10 mcg/kg iv bolus then 50 mcg/kg/h infusion). 14C-deoxyglucose autoradiography was performed 45 min after controlled cortical impact (CCI) to left parietal cortex (n=4 per anesthetic group) or in uninjured rats after 45 min of anesthesia (n=3 per anesthetic group). Uninjured rats treated with fentanyl vs. isoflurane showed 35-45% higher CMRglu in all brain structures (p<0.05) except CA3. After TBI in rats treated with isoflurane, CMRglu increased significantly only in ipsilateral CA1 and ipsilateral parietal cortex (p<0.05 vs. isoflurane uninjured). Conversely, after TBI in rats treated with fentanyl, CMRglu increased markedly and bilaterally in CA1 and CA3 (p<0.05 vs. fentanyl uninjured), but not ipsilateral parietal cortex. In contralateral CA1, CMRglu was nearly two times greater after TBI in fentanyl vs. isoflurane treated rats (p<0.05). Hyperglycolysis was exacerbated in CA1 and CA3 hippocampus after TBI in rats treated with fentanyl vs. isoflurane anesthesia. This post-traumatic hyperglycolysis suggests greater excitotoxicity and concurs with reports of worse functional outcome and more CA1 hippocampal death after TBI with fentanyl vs. isoflurane anesthesia.

  4. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    DTIC Science & Technology

    2015-03-01

    shockwave . Rats were exposed to two closely coupled shockwaves (peak total pressures of S, 12 or 19 psi) separated by 30 sec. Rats were euthanized at...position 2.S ft w ithin the mouth of a 1 ft diameter shock tube with the r ight side of the animal facing the oncoming shockwave . Rats were exposed to two...closely coupled shockwaves (peak total pressures of S, 12 or 19 psi) separated by 30 sec. Rats were euthanized at varied intervals post-injury and

  5. The influence of microwave radiation from cellular phone on fetal rat brain.

    PubMed

    Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

    2012-03-01

    The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (P<0.05) found in the contents of SOD, GSH-Px, and MDA in GM and GH; the contents of SOD and GSH-Px decreased and the content of MDA increased. The significant content differences of NE and DA were found in fetal rat brains in GL and GH groups, with the GL group increased and the GH group decreased. Through this study, we concluded that receiving a certain period of microwave radiation from cellular phones during pregnancy has certain harm on fetal rat brains.

  6. Neuroplasticity Changes of Rat Brain by Musical Stimuli during Fetal Period

    PubMed Central

    Sheikhi, Siamak; Saboory, Ehsan

    2015-01-01

    Objective Fetal development of the central nervous system is an important and sensitive stage which is affected by many external and internal stimuli. This study aimed to investigate effect of musical stimuli on fetal rat brain. Materials and Methods In this experimental study, twelve female Wistar rats were selected and evenly assigned to control and musical groups. The females were mated with a male rat of the same genotype. Musical group was exposed to classic music with 60 dB power for 90 minutes twice per day from 2nd to 20th day of gestation. The control rats were handled similar to the musical group, but were not exposed to music. Before parturition, all the dams were anesthetized, and their blood samples were obtained and used for corticosterone (COS) measurement. They were transcardially perfused by electron microscope (EM) fixative agent. The fetal brains were extracted intact and used for slice preparation. Horizontal slices were made for electron microscope preparation, and images were taken and analyzed in terms of cell density and morphological changes. Results EM observation indicated significant morphological difference in cellular and intercellular spaces between the two groups. Music-treated fetuses had significantly higher cell density in parietal cortex and music-treated dams had lower COS level. Conclusion It was concluded that prenatal music would have a great impact on neuroplasticity of fetal rat brain, at least indirectly. Although the rat fetuses cannot hear until birth, music-induced reduction in COS blood level of dams might be the reason for neuroplasticity of fetal brain. PMID:25685735

  7. Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

    2011-12-01

    Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

  8. Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

    PubMed

    Gray, Jason D; Punsoni, Michael; Tabori, Nora E; Melton, Jay T; Fanslow, Victoria; Ward, Mary J; Zupan, Bojana; Menzer, David; Rice, Jackson; Drake, Carrie T; Romeo, Russell D; Brake, Wayne G; Torres-Reveron, Annelyn; Milner, Teresa A

    2007-07-04

    Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.

  9. Neuroprotection by acetyl-L-carnitine after traumatic injury to the immature rat brain.

    PubMed

    Scafidi, Susanna; Racz, Jennifer; Hazelton, Julie; McKenna, Mary C; Fiskum, Gary

    2010-01-01

    Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-L-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21-22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3-7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was significantly

  10. Neuroprotection by Acetyl-l-Carnitine after Traumatic Injury to the Immature Rat Brain

    PubMed Central

    Scafidi, Susanna; Racz, Jennifer; Hazelton, Julie; McKenna, Mary C.; Fiskum, Gary

    2011-01-01

    Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and is characterized by reduced aerobic cerebral energy metabolism early after injury, possibly due to impaired activity of the pyruvate dehydrogenase complex. Exogenous acetyl-l-carnitine (ALCAR) is metabolized in the brain to acetyl coenzyme A and subsequently enters the tricarboxylic acid cycle. ALCAR administration is neuroprotective in animal models of cerebral ischemia and spinal cord injury, but has not been tested for TBI. This study tested the hypothesis that treatment with ALCAR during the first 24 h following TBI in immature rats improves neurologic outcome and reduces cortical lesion volume. Postnatal day 21–22 male rats were isoflurane anesthetized and used in a controlled cortical impact model of TBI to the left parietal cortex. At 1, 4, 12 and 23 h after injury, rats received ALCAR (100 mg/kg, intraperitoneally) or drug vehicle (normal saline). On days 3–7 after surgery, behavior was assessed using beam walking and novel object recognition tests. On day 7, rats were transcardially perfused and brains were harvested for histological assessment of cortical lesion volume, using stereology. Injured animals displayed a significant increase in foot slips compared to sham-operated rats (6 ± 1 SEM vs. 2 ± 0.2 on day 3 after trauma; n = 7; p < 0.05). The ALCAR-treated rats were not different from shams and had fewer foot slips compared to vehicle-treated animals (2 ± 0.4; n = 7; p< 0.05). The frequency of investigating a novel object for saline-treated TBI animals was reduced compared to shams (45 ± 5% vs. 65 ± 10%; n = 7; p < 0.05), whereas the frequency of investigation for TBI rats treated with ALCAR was not significantly different from that of shams but significantly higher than that of saline-treated TBI rats (68 ± 7; p < 0.05). The left parietal cortical lesion volume, expressed as a percentage of the volume of tissue in the right hemisphere, was

  11. Effects of Aquaporin 4 Knockdown on Brain Edema of the Uninjured Side After Traumatic Brain Injury in Rats

    PubMed Central

    Chen, Jian-Qiang; Zhang, Cheng-Cheng; Jiang, Sheng-Nan; Lu, Hong; Wang, Wei

    2016-01-01

    Background Traumatic brain injury (TBI) induces edema on the uninjured side (i.e., contralateral brain tissue; CBT). We evaluated the role of AQP4 in CBT edema formation following TBI. Material/Methods Mild or severe TBI was induced using a controlled cortical impact model in rats, immediately followed by intraventricular siRNA infusions. The effects of AQP4 siRNA on CBT edema were assessed at up to 168 h. Results Mild or severe TBI induced different patterns of CBT edema. Furthermore, following mild TBI, brain water content (BWC) was increased at 72 h thereafter and AQP4 expression was increased after 168 h, relative to non-injured rats (i.e., sham). AQP4 interference reduced AQP4 expression 48 h thereafter and BWC 72 h thereafter, relative to control siRNA. In contrast, following severe TBI, BWC was increased 1 h thereafter and AQP4 expression was transiently enhanced after 1 h, relative to sham. However, AQP4 interference reduced AQP4 expression after 1 h and BWC 24 h thereafter, relative to control siRNA. Finally, apparent diffusion coefficient (ADC) value in CBT was positively correlated with AQP4 expression level following severe, but not mild, TBI. AQP4 interference disrupted this correlation. Conclusions AQP4 interference reduces CBT edema formation, and ADC value may predict TBI severity. PMID:27930615

  12. Treatment of traumatic brain injury with thymosin β4 in rats

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Meng, Yuling; Zhang, Yanlu; Zhang, Zheng Gang; Morris, Daniel C.; Chopp, Michael

    2010-01-01

    Object This study was designed to investigate the efficacy of delayed thymosin β4 (TB4) treatment of traumatic brain injury (TBI) in rats. Methods Young adult male Wistar rats were divided into the following groups: 1) Sham group (6 rats); 2) TBI + Saline group (9 rats); 3) and TBI + Tβ4 group (10 rats). TBI was induced by controlled cortical impact over the left parietal cortex. Thymosin β4 (6 mg/kg) or saline was administered intraperitoneally starting at Day 1 and then every 3 days for an additional 4 doses. Neurological function was assessed using a modified neurological severity score (mNSS), footfault and Morris water maze tests. Animals were killed 35 days after injury, and brain sections stained for immunohistochemistry to assess angiogenesis, neurogenesis, and oligodendrogenesis after Tβ4 treatment. Results Compared to the saline treatment, delayed Tβ4 treatment did not affect lesion volume but significantly reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, increased oligodendrogenesis in the CA3 region, and significantly improved sensorimotor functional recovery and spatial learning. Conclusions These data for the first time demonstrate that delayed administration of Tβ4 significantly improves histological and functional outcomes in rats with TBI, indicating that Tβ4 has considerable therapeutic potential for patients with TBI. PMID:20486893

  13. Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats

    PubMed Central

    Brady, R.D.; Grills, B.L.; Romano, T.; Wark, J.D.; O’Brien, T.J.; Shultz, S.R.; McDonald, S.J.

    2016-01-01

    Objectives: Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. Methods: Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. Results: Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. Conclusion: These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI. PMID:27973389

  14. The physiologically induced release of ascorbate in rat brain is dependent on impulse traffic, calcium influx and glutamate uptake.

    PubMed

    Miele, M; Boutelle, M G; Fillenz, M

    1994-09-01

    Extracellular brain ascorbate fluctuates with neuronal activity. There is previous evidence that the release of ascorbate is triggered by the re-uptake of neuronally released glutamate. This hypothesis predicts that drugs which block the release and re-uptake of glutamate will also block the release of ascorbate. In the present experiments we have used a novel dialysis electrode which allows continuous monitoring of physiologically induced ascorbate release from the striatum in freely moving rats. An infusion of the enzyme ascorbic acid oxidase abolished the increase in oxidation current in response to tail-pinch, which identified it as an ascorbate current. Perfusion with tetrodotoxin reduced the response to 25% and with CdCl2 to 4% of control. Perfusion with the uptake blocker L-trans-pyrrolidine-2,4-di-carboxylate reduced the response to 24% of control. A neuroprotective function for this coupling of ascorbate and glutamate release is discussed.

  15. Flexible Coupling of Respiration and Vocalizations with Locomotion and Head Movements in the Freely Behaving Rat

    PubMed Central

    Alves, Joseph Andrews; Boerner, Barbara Ciralli

    2016-01-01

    Quadrupedal mammals typically synchronize their respiration with body movements during rhythmic locomotion. In the rat, fast respiration is coupled to head movements during sniffing behavior, but whether respiration is entrained by stride dynamics is not known. We recorded intranasal pressure, head acceleration, instantaneous speed, and ultrasonic vocalizations from male and female adult rats while freely behaving in a social environment. We used high-speed video recordings of stride to understand how head acceleration signals relate to locomotion and developed techniques to identify episodes of sniffing, walking, trotting, and galloping from the recorded variables. Quantitative analysis of synchrony between respiration and head acceleration rhythms revealed that respiration and locomotion movements were coordinated but with a weaker coupling than expected from previous work in other mammals. We have recently shown that rats behaving in social settings produce high rates of ultrasonic vocalizations during locomotion bouts. Accordingly, rats emitted vocalizations in over half of the respiratory cycles during fast displacements. We present evidence suggesting that emission of these calls disrupts the entrainment of respiration by stride. The coupling between these two variables is thus flexible, such that it can be overridden by other behavioral demands. PMID:27525126

  16. Neuron-astrocyte interactions, pyruvate carboxylation and the pentose phosphate pathway in the neonatal rat brain.

    PubMed

    Morken, Tora Sund; Brekke, Eva; Håberg, Asta; Widerøe, Marius; Brubakk, Ann-Mari; Sonnewald, Ursula

    2014-01-01

    Glucose and acetate metabolism and the synthesis of amino acid neurotransmitters, anaplerosis, glutamate-glutamine cycling and the pentose phosphate pathway (PPP) have been extensively investigated in the adult, but not the neonatal rat brain. To do this, 7 day postnatal (P7) rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate and sacrificed 5, 10, 15, 30 and 45 min later. Adult rats were injected and sacrificed after 15 min. To analyse pyruvate carboxylation and PPP activity during development, P7 rats received [1,2-(13)C]glucose and were sacrificed 30 min later. Brain extracts were analysed using (1)H- and (13)C-NMR spectroscopy. Numerous differences in metabolism were found between the neonatal and adult brain. The neonatal brain contained lower levels of glutamate, aspartate and N-acetylaspartate but similar levels of GABA and glutamine per mg tissue. Metabolism of [1-(13)C]glucose at the acetyl CoA stage was reduced much more than that of [1,2-(13)C]acetate. The transfer of glutamate from neurons to astrocytes was much lower while transfer of glutamine from astrocytes to glutamatergic neurons was relatively higher. However, transport of glutamine from astrocytes to GABAergic neurons was lower. Using [1,2-(13)C]glucose it could be shown that despite much lower pyruvate carboxylation, relatively more pyruvate from glycolysis was directed towards anaplerosis than pyruvate dehydrogenation in astrocytes. Moreover, the ratio of PPP/glucose-metabolism was higher. These findings indicate that only the part of the glutamate-glutamine cycle that transfers glutamine from astrocytes to neurons is operating in the neonatal brain and that compared to adults, relatively more glucose is prioritised to PPP and pyruvate carboxylation. Our results may have implications for the capacity to protect the neonatal brain against excitotoxicity and oxidative stress.

  17. A simple method for isolating and culturing the rat brain microvascular endothelial cells.

    PubMed

    Liu, Yang; Xue, Qiang; Tang, Qing; Hou, Min; Qi, Hongyi; Chen, Gang; Chen, Weihai; Zhang, Jifen; Chen, Yi; Xu, Xiaoyu

    2013-11-01

    Brain microvascular endothelial cells (BMECs), a main component of the blood-brain barrier, play a critical role in the pathogenesis of many brain diseases. The primary culture of BMECs has been used in various models for studying cerebrovascular diseases in vitro. However, there are still several problems existing in the isolation and cultivation of primary rat BMECs, such as low yield, contamination with other cell types, and requirement of a large number of animals and expensive growth factor. In this study, we describe a simple, economical (without any growth factor) and repeatable method to obtain endothelial cells with high purity (>99%) and yield (about 2.2×10(7) per rat) from cerebral cortexes of neonatal rat, mainly from gray matter. In vitro examinations determined that the isolated cells expressed typical phenotypic markers of differentiated brain endothelium such as multiple drug resistant protein, von Willebrand factor, platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31), and intercellular adhesion molecule (ICAM). These cells also possessed morphological and ultra-structural characteristics that were observed by phase contrast microscope and electric microscope. Then GFAP and α-SMA were used, respectively, to identify astrocyte and pericyte which were potential to contaminate primary culturing of BMECs. And specific reaction of endothelial cells to external stimulation was tested by culture with TNF-α for 24h. All these results of our experiments supply that our protocol provides an effective and reliable method to obtain high purity and yield of rat BMECs and offers a useful tool for studying cellular physiology, cerebrovascular diseases, brain tumors, blood-brain barrier and neurovascular units, etc.

  18. Adenosine transport systems on dissociated brain cells from mouse, guinea-pig, and rat

    SciTech Connect

    Johnston, M.E.; Geiger, J.D. )

    1990-09-01

    The kinetics and sodium dependence of adenosine transport were determined using an inhibitor-stop method on dissociated cell body preparations obtained from mouse, guinea-pig and rat brain. Transport affinity (KT) values for the high affinity adenosine transport systems KT(H) were significantly different between these three species; mean +/- SEM values were 0.34 +/- 0.1 in mouse, 0.9 +/- 0.2 in rat, and 1.5 +/- 0.5 microM in guinea-pig. The KT values for the low affinity transport system KT(L) were not different between the three species. Brain cells from rat displayed a significantly greater maximal capacity to accumulate (3H)adenosine (Vmax) than did mouse or guinea-pig for the high affinity system, or than did mouse for the low affinity system. When sodium chloride was replaced in the transport medium with choline chloride, the KT(H) values for guinea-pig and rat were both increased by approximately 100%; only in rat did the change reach statistical significance. The sodium-dependence of adenosine transport in mouse brain was clearly absent. The differences between KT(H) values in mouse and those in guinea-pig or rat were accentuated in the absence of sodium. The differences in kinetic values, ionic requirements, and pharmacological characteristics between adenosine transporters in CNS tissues of mouse, guinea-pig and rat may help account for some of the variability noted among species in terms of their physiological responses to adenosine.

  19. Direct nose-brain transport of benzoylecgonine following intranasal administration in rats.

    PubMed

    Chow, H H; Anavy, N; Villalobos, A

    2001-11-01

    In our previous research, cocaine applied intranasally in rats diffused or was transported directly from the nasal cavity to the brain. However, the direct nose-brain cocaine transport only contributes to an initial increase in the relative cocaine brain exposure. In this study, we have determined the nose-brain transport of a polar metabolite of cocaine, benzoylecgonine, to help understand factors affecting drug transport via this novel pathway. The nasal cavity of male Sprague-Dawley rats was isolated to prevent drainage of nasally applied dosing solution to non-nasal regions. Benzoylecgonine was then administered, either by intranasal administration or by intravenous (iv) injection. At different times postdose, blood and tissues from different regions of the brain were collected from groups of rats (n = 4 for each collection time) and benzoylecgonine concentrations in these samples were analyzed by high-performance liquid chromatography. Benzoylecgonine concentrations in plasma were at maximal levels immediately after iv dosing and declined as a function of time. Following intranasal administration, benzoylecgonine concentrations in plasma reached maximal levels between 15 and 30 min after dosing and declined as a function of time. To allow comparison of brain benzoylecgonine content after iv and intranasal administration, brain benzoylecgonine contents were normalized by plasma benzoylecgonine concentrations. The ratios of the area under the benzoylecgonine concentration-time curve (AUC) between the olfactory bulb and plasma following intranasal administration were 10-100 times higher than those obtained after iv dosing. The olfactory tract-to-plasma benzoylecgonine AUC ratios after intranasal administration were significantly higher than those after iv dosing up to 120 min following dosing. The brain tissue-to-plasma AUC ratios in cerebellum, brain stem, and cerebral cortex after intranasal administration were significantly higher than the corresponding ratios

  20. Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

    PubMed Central

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  1. Enriched environment increases myelinated fiber volume and length in brain white matter of 18-month female rats.

    PubMed

    Yang, Shu; Lu, Wei; Zhou, De-shan; Tang, Yong

    2015-04-23

    Cognition and memory decline with normal aging, which could be partly attributed to the degeneration of brain white matter. Previous studies demonstrated that exposure to an enriched environment (EE) could protect cognition and memory from aging. However, if or how EE might affect the brain white matter has not been thoroughly investigated. In the current study, 24 middle-aged (14-month-old) female Sprague -Dawley (SD) rats were randomly assigned to EE or standard environment (SE) for 4 months. At the end of the environment intervention, the Morris water maze tests were performed. Then, 5 rats were randomly selected from each group for stereological assessment of the brain white matter and its myelinated fibers. The results revealed that middle-aged rats living in EE displayed better spatial learning than SE controls. The white matter volume was 124.6 ± 7.8mm(3) in EE rats, which was significantly enlarged compared with 84.8 ± 3.4mm(3) in SE rats. Likewise, the myelinated fiber volume was markedly increased from 56.6 ± 1.7 mm(3) in SE rats to 87.2 ± 9.0mm(3) in EE rats; so was the myelinated fiber length from 83.5 ± 6.6 km in SE rats to 119.0 ± 10.0 km in EE rats. Our data suggested that EE could protect brain white matter and its myelinated fibers of female rats at middle age.

  2. Energy metabolism in rat brain: inhibition of pyruvate decarboxylation by 3-hydroxybutyrate in neonatal mitochondria.

    PubMed

    Booth, R F; Clark, J B

    1981-07-01

    The effect of 3-hydroxybutyrate on pyruvate decarboxylation by neonatal rat brain mitochondria and synaptosomes was investigated. The rate of [1-14C]pyruvate decarboxylation (1 mM final concentration) by brain synaptosomes derived from 8-day-old rats was inhibited by 10% in the presence of 2 mM-D,L-3-hydroxybutyrate and by more than 20% in the presence of 20 mM D,L-3-hydroxybutyrate. The presence of 2 mM-D,L-3-hydroxybutyrate did not affect the rate of [1-14C]pyruvate decarboxylation (1 mM final concentration) by brain mitochondria; however, at a concentration of 20 mM-D,L-3-hydroxybutyrate, a marked inhibition was seen in preparations from both 8-hydroxybutyrate, a marked inhibition was seen in preparations from both 8-day-old (35% inhibition) and 21-day-old (24% inhibition) but not in those from adult rats. Although the presence of 100 mM-K+ in the incubation medium stimulated the rate of pyruvate decarboxylation by approximately 50% compared with the rate in presence of 1 mM-K+, the presence of 20 mM-D,L-3-hydroxybutyrate still caused a marked inhibition in both media (1 and 100 mM-K+). The presence of 20 mM-D,L-3-hydroxybutyrate during the incubation caused an approximately 20% decrease in the level of the active form of the pyruvate dehydrogenase complex in brain mitochondria from 8-day-old rats. The concentrations of ATP, ADP, NAD+, NADH, acetyl CoA, and CoA were measured in brain mitochondria from 8-day-old rats incubated in the presence of 1 mM-pyruvate alone or 1 mM-pyruvate plus 20 mM-D,L-3-hydroxybutyrate. Neither the APT/ADP nor the NADH/NAD+ ratio showed significant changes. The acetyl CoA/CoA ratio was significantly increased by more than twofold in the presence of 3-hydroxybutyrate. The possible mechanisms and physiological significance of 3-hydroxybutyrate inhibition of pyruvate decarboxylation in neonatal rat brain rat mitochondria are discussed.

  3. Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA.

    PubMed Central

    Schneider, J W; Mercer, R W; Caplan, M; Emanuel, J R; Sweadner, K J; Benz, E J; Levenson, R

    1985-01-01

    We have isolated a cDNA clone for the rat brain Na,K-ATPase alpha subunit. A lambda gt11 cDNA expression library constructed from mRNA of 1- and 2-week-old rat brains was screened with an antibody reactive with rat brain Na,K-ATPase. A positive phage clone, lambda rb5, containing a 1200-base-pair cDNA insert expressed a beta-galactosidase-cDNA fusion protein that was reactive by immunoblotting with the Na,K-ATPase antibody. This fusion protein was also reactive in ELISA with a monoclonal antibody directed against the alpha subunit of the Na,K-ATPase. A 27S mRNA species exhibiting sequence hybridization to the cDNA insert of lambda rb5 was identified in rat brain, kidney, and liver, as well as in dog kidney. This 27S mRNA exhibited a tissue-specific pattern of abundance consistent with the relative abundance of Na,K-ATPase polypeptides in vivo: kidney greater than brain greater than liver. In a ouabain-resistant HeLa cell line, C+, which contains minute chromosomes and at least a 10-fold greater number of sodium pumps than parental HeLa cells, DNA sequences complementary to lambda rb5 cDNA were amplified approximately 40-fold. Analysis of the lambda rb5 cDNA sequence demonstrated a perfect nucleotide sequence match between a portion of the cDNA and the amino acid sequence of the Na,K-ATPase alpha-subunit fluorescein isothiocyanate binding site. Taken together, the data presented here demonstrate that the lambda rb5 cDNA clone is a portion of the gene coding for the rat brain Na,K-ATPase alpha subunit. The ATPase gene appears to be present in one or very few copies in the rat and human genomes and to be transcriptionally regulated in different rat tissues. In a ouabain-resistant human cell line, on the other hand, ouabain resistance appears to involve an increase in the number of gene copies coding for the Na,K-ATPase. Images PMID:2994074

  4. Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain.

    PubMed Central

    de Lange, E. C.; Bouw, M. R.; Mandema, J. W.; Danhof, M.; de Boer, A. G.; Breimer, D. D.

    1995-01-01

    1. The purpose of the present study was to determine whether intracerebral microdialysis can be used for the assessment of local differences in drug concentrations within the brain. 2. Two transversal microdialysis probes were implanted in parallel into the frontal cortex of male Wistar rats, and used as a local infusion and detection device respectively. Within one rat, three different concentrations of atenolol or acetaminophen were infused in randomized order. By means of the detection probe, concentration-time profiles of the drug in the brain were measured at interprobe distances between 1 and 2 mm. 3. Drug concentrations were found to be dependent on the drug as well as on the interprobe distance. It was found that the outflow concentration from the detection probe decreased with increasing lateral spacing between the probes and this decay was much steeper for acetaminophen than for atenolol. A model was developed which allows estimation of kbp/Deff (transfer coefficient from brain to blood/effective diffusion coefficient in brain extracellular fluid), which was considerably larger for the more lipohilic drug, acetaminophen. In addition, in vivo recovery values for both drugs were determined. 4. The results show that intracerebral microdialysis is able to detect local differences in drug concentrations following infusion into the brain. Furthermore, the potential use of intracerebral microdialysis to obtain pharmacokinetic parameters of drug distribution in brain by means of monitoring local concentrations of drugs in time is demonstrated. PMID:8581296

  5. Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury.

    PubMed

    Li, Yafei; Li, Xihong; Qu, Yi; Huang, Jichong; Zhu, Tingting; Zhao, Fengyan; Li, Shiping; Mu, Dezhi

    2017-04-03

    High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.

  6. A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.

    PubMed

    Kharatishvili, I; Nissinen, J P; McIntosh, T K; Pitkänen, A

    2006-06-30

    Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.

  7. Effect of amantadine sulphate on intracerebral hemorrhage-induced brain injury in rats.

    PubMed

    Titova, E; Ostrowski, R P; Zhang, J H; Tang, J

    2008-01-01

    Recent studies have shown that amantadine, an uncompetitive N-methyl-d-aspartate receptor antagonist and dopamine agonist, is effective for the treatment of various cerebral disorders and causes relatively mild side effects. In this study, we investigated whether administration of amantadine will provide a neuroprotective effect in the intracerebral hemorrhage (ICH) rat model. A total of 15 male Sprague Dawley rats (300-380 g) were divided into sham, ICH-untreated, and ICH-treated with amantadine sulphate groups. ICH was induced by collagenase injection. Total dose 6 mg/kg of amantadine sulphate was divided into 3 injections and administered intraperitoneally at 1, 8, and 16 h after ICH. Brain injury was evaluated by investigating neurological function and brain edema at 24 h after ICH. Our data demonstrates that ICH caused significant neurological deficit associated with marked brain edema. Amantadine did not reduce brain injury after ICH; neurological function and brain edema in the treated group were not different from those of the untreated group. We conclude that amantadine sulphate does not offer neuroprotection in acute stage of experimental ICH-induced brain injury.

  8. Hesperidin, an antioxidant flavonoid, prevents acrylonitrile-induced oxidative stress in rat brain.

    PubMed

    El-Sayed, El-Sayed M; Abo-Salem, Osama M; Abd-Ellah, Mohamed F; Abd-Alla, Gamil M

    2008-01-01

    Acrylonitrile (ACN) is a volatile, toxic liquid used as a monomer in the manufacture of synthetic rubber, styrene plastics, acrylic fiber, and adhesives. ACN is a potent neurotoxin. A role for free radical mediated lipid peroxidation in the toxicity of ACN has been suggested. We examined the ability of hesperidin, an antioxidant flavonoid, to attenuate ACN-induced alterations in lipid peroxidation in rat brains. The daily oral administration of ACN to male albino rats in a dose of 50 mg/kg bwt for a period of 28 days produced a significant elevation in brain lipid peroxides measured as malondialdehyde (MDA) amounting to 107%, accompanied by a marked decrease in brain-reduced glutathione (GSH) content reaching 63%. In addition, ACN administration resulted in significant reductions in the enzymatic antioxidant parameters of brain; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST) recording 43%, 64%, 52%, and 43%, respectively. On the other hand, pretreatment with hesperidin and its coadministration with ACN once daily in a dose of 200 mg/kg bwt i.p. for 28 days ameliorated ACN-induced alterations in brain lipid peroxidation. These results suggest that hesperidin may have a beneficial role against ACN-induced oxidative stress in the brain; an effect that is mainly attributed to the antioxidant property of hesperidin.

  9. Transferrin receptors in rat brain: neuropeptide-like pattern and relationship to iron distribution.

    PubMed Central

    Hill, J M; Ruff, M R; Weber, R J; Pert, C B

    1985-01-01

    We have characterized and visualized the binding of 125I-labeled transferrin to sections of rat brain. This saturable, reversible, high-affinity (Kd = 1 X 10(-9) M) binding site appears indistinguishable from transferrin receptors previously characterized in other tissues. Moreover, a monoclonal antibody raised to rat lymphocyte transferrin receptors could immunoprecipitate recovered intact transferrin solubilized from labeled brain slices, indicating that labeling was to the same molecular entity previously characterized as the transferrin receptor. The pattern of transferrin receptor distribution visualized in brain with both 125I-labeled transferrin and an anti-transferrin receptor monoclonal antibody are almost indistinguishable but differ from the pattern of iron distribution. Iron-rich brain areas generally receive neuronal projections from areas with abundant transferrin receptors, suggesting that iron may be transported neuronally. However, many brain areas with a high density of transferrin receptors appear unrelated to iron uptake and neuronal transport and form a receptor distribution pattern similar to that of other known neuropeptides. This "neuropeptide-like" distribution pattern suggests that transferrin may have neuromodulatory, perhaps behavioral, function in brain. Images PMID:2989832

  10. Changes in alpha-fetoprotein and albumin synthesis rates and their levels during fetal and neonatal development of rat brain.

    PubMed

    Ali, M; Sahib, M K

    1983-02-01

    An attempt was made to find a correlation between AFP and albumin levels in brain and their rates of synthesis in the brain cells during maturation of rat brain. Levels of alpha-fetoprotein (AFP) and albumin in the developing brain were studied by rocket immunoassay. Rate of synthesis of AFP and albumin in brain cell cultures, established from rat brain at various stages of development, were determined by incorporation of [14C]leucine into immuno-precipitable intracellular AFP and albumin. AFP and albumin levels in brain as well as rates of their synthesis by brain cells in culture registered a continuous decline during development. Synthesis of AFP and albumin in the brain is switched off after first week of postnatal life with a concomitant disappearance of these proteins from the brain. Levels of AFP and albumin in brain correlated well with rates of their synthesis by brain cells in vitro at any specific stage of brain maturation implying that levels of AFP and albumin in brain are regulated by controlling rates of their synthesis in the maturing brain cells.

  11. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    DTIC Science & Technology

    2014-03-01

    combat are exposed to a brain insult resulting from a combination of both a shock wave and biomechanical perturbation related to rapid acceleration...blast waves affect the brain along with diagnosing mbTBI are still a matter of considerable debate. The abovementioned caveats underline the...AD Award Number: W81XWH-11-2-0127 TITLE: Combined Effects of Primary and Tertiary Blast on Rat Brain : Characterization of a Model of

  12. The effects of hyperthermia and hyperthermia plus microwaves on rat brain energy metabolism

    SciTech Connect

    Sanders, A.P.; Joines, W.T.

    1984-01-01

    The effects of hyperthermia, alone and in conjunction with microwave exposure, on brain energetics were studied in anesthetized male Sprague-Dawley rats. The effect of temperature on adenosine triphosphate concentration (ATP) and creatine phosphate concentration (CP) was determined in the brains of rats that were maintained at 35.6, 37.0, 39.0, and 41.0 degrees C. At 37, 39, and 41 degrees C brain (ATP) and (CP) were down 6.0, 10.8, and 29.2%, and 19.6, 28.7, and 44%, respectively, from the 35.6 degrees C control concentrations. Exposure of the brain to 591-MHz radiation at 13.8 mW/cm2 for 0.5, 1.0, 3.0, and 5.0 min caused further decreases (below those observed for 30 degrees C hyperthermia only) of 16.0, 29.8, 22.5, and 12.3% in brain (ATP), and of 15.6, 25.1, 21.4, and 25.9% in brain (CP) after 0.5, 1.0, 3.0, and 5.0 min, respectively. Recording of brain reduced nicotinamide adenine dinucleotide (NADH) fluorescence before, during, and after microwave exposure showed an increase in NADH fluorescence during microwave exposure that returned to preexposure levels within 1 min postexposure. Continuous recording of brain temperatures during microwave exposures showed that brain temperature varied between -0.1 and +0.05 degrees C. Since the microwave exposures did not induce tissue hyperthermia, it is concluded that direct microwave interaction at the subcellular level is responsible for the observed decrease in (ATP) and (CP).

  13. Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the injured rat brain

    NASA Astrophysics Data System (ADS)

    Lin, Yong; Pan, Yaohua; Shi, Yinfeng; Huang, Xianjian; Jia, Nengqin; Jiang, Ji-yao

    2012-04-01

    Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied to deliver small-molecule drugs to the central nervous system (CNS). However, it is unclear whether PBCA nanoparticles can be used as the delivery system for large molecules to potentially treat traumatic brain injury (TBI). In this study, we tested the capacity of PBCA nanoparticles in passing through the blood-brain barrier (BBB) and transporting large molecules into normal and injured brains in the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and then loaded the particles with either horseradish peroxidase (HRP, 44 kDa) or enhanced green fluorescent protein (EGFP, 29 kDa), which were further coated with polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA nanoparticles were intravenously injected into the normal and brain-injured rats. We found that, at 45 min after injection, PBCA nanoparticle-delivered HRP or EGFP was hardly detected in the normal brains of the rats, but a small amount of EGFP carried by PBCA nanoparticles was noted in the normal brains 48 h after administration, which was further confirmed by immunolocalization with anti-EGFP antibodies. In contrast, at 4 h after TBI with a circulation time of 45 min, although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA nanoparticle-delivered HRP or EGFP was widely distributed near injured sites. Together, our findings provide histological evidence that PBCA nanoparticles can be used as an efficient delivery system for large molecules to overcome the barrier in the brain with TBI.

  14. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  15. Response of rat brain protein synthesis to ethanol and sodium barbital

    SciTech Connect

    Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

    1987-01-01

    Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of /sup 14/C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the /sup 14/C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of /sup 14/C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units.

  16. Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats.

    PubMed

    Kaczorowski, S L; Schiding, J K; Toth, C A; Kochanek, P M

    1995-09-01

    As part of the acute inflammatory response, neutrophils accumulate in the central nervous system after injury. Recently, a soluble human recombinant complement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alternative pathways of complement. sCR1 attenuates the effects of the acute inflammatory response in several models of injury outside the central nervous system. The role of complement in traumatic brain injury, however, remains undefined. We hypothesized that treatment with sCR1 would attenuate neutrophil accumulation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague-Dawley rats were pre-treated with sCR1 or saline (control) at both 2 h and 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCR1 (or saline) was given 6 h after trauma. Coronal brain sections centered on the site of trauma were obtained at 24 h after trauma and analyzed for myeloperoxidase (MPO) activity as a marker of neutrophil accumulation. Complete blood counts with differential were obtained before treatment with sCR1 and at 24 h after trauma. At 24 h after trauma, brain MPO activity was reduced by 41% in sCR1-treated rats compared with control rats [0.1599 +/- 0.102 versus 0.2712 +/- 0.178 U/g (mean +/- SD); p = 0.02]. The neutrophil count in peripheral blood increased approximately twofold in both groups. Neutrophil accumulation occurring in the brain after trauma is inhibited by sCR1 treatment. This suggests that complement activation is involved in the local inflammatory response to traumatic brain injury and plays an important role in neutrophil accumulation in the injured brain.

  17. Mesenchymal stem cells restore orientation and exploratory behavior of rats after brain injury.

    PubMed

    Sokolova, I B; Fedotova, O R; Tsikunov, S G; Polyntsev, D G

    2011-05-01

    We studied the effects of intravenous and intracerebral transplantation of MSC on restoration of orientation and exploratory behavior of Wistar-Kyoto rats after removal of the left motor cortex. Removal of the motor cortex led to a significant reduction of the number of behavioral acts in the open field test. Two weeks after removal of the motor cortex and intravenous transplantation, the animals were as inhibited as the controls, but during the next 10 weeks, the behavioral status of these rats remained unchanged, while controls exhibited further behavioral degradation. After injection of MSC into the brain, the behavior of rats with trauma did not change in comparison with intact rats over 10 weeks.

  18. Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

    SciTech Connect

    Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

    1986-03-01

    A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake.

  19. Sodium butyrate reverses the inhibition of Krebs cycle enzymes induced by amphetamine in the rat brain.

    PubMed

    Valvassori, Samira S; Calixto, Karen V; Budni, Josiane; Resende, Wilson R; Varela, Roger B; de Freitas, Karolina V; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2013-12-01

    There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.

  20. Effects of delayed treatment with nebracetam on neurotransmitters in brain regions after microsphere embolism in rats

    PubMed Central

    Takeo, Satoshi; Hayashi, Hideki; Miyake, Keiko; Takagi, Kaori; Tadokoro, Mina; Takagi, Norio; Oshikawa, Sayuri

    1997-01-01

    The effects of delayed treatment with nebracetam, a novel nootropic drug, on neurotransmitters of brain regions were examined in rats with microsphere embolism-induced cerebral ischaemia. Cerebral ischaemia was induced by administration of 900 microspheres (48 μm) into the internal carotid artery. The rats with stroke-like symptoms were treated p.o. with 30 mg kg−1 nebracetam twice daily. The levels of acetylcholine, dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and their metabolites in the cerebral cortex, striatum and hippocampus of animals with microsphere embolism were determined by high performance liquid chromatography (h.p.l.c.) on the 3rd and 7th days after the operation. Although the microsphere embolism induced significant changes in most of the neurotransmitters and some of their metabolites in the brain regions, the delayed treatment with nebracetam partially restored only the hippocampal 5-HT and the striatal dopamine metabolite contents on the 3rd day. The hippocampal in vivo 5-HT synthesis, but not the striatal dopamine synthesis, was attenuated in rats with microsphere embolism on the 3rd day, but was restored by treatment with nebracetam. In vivo striatal dopamine turnover rate of the rats with microsphere embolism was inhibited on the 3rd day irrespective of treatment with nebracetam. The present study provides evidence for a possible action of nebracetam on 5-HT metabolism in the ischaemic brain. PMID:9179389

  1. The Effect of Electric Cortical Stimulation after Focal Traumatic Brain Injury in Rats

    PubMed Central

    Yoon, Yong-Soon; Yu, Ki Pi; Kim, Hyojoon; Kim, Hyoung-ihl; Kim, Bong Ok

    2012-01-01

    Objective To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. Method Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 µs duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. Results There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. Conclusion Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods. PMID:23185723

  2. Curcumin Mediated Attenuation of Carbofuran Induced Oxidative Stress in Rat Brain

    PubMed Central

    Jaiswal, Sunil Kumar; Sharma, Ashish; Gupta, Vivek Kumar; Singh, Rakesh Kumar; Sharma, Bechan

    2016-01-01

    The indiscriminate use of carbofuran to improve crop productivity causes adverse effects in nontargets including mammalian systems. The objective of this study was to evaluate carbofuran induced oxidative stress in rat brain stem and its attenuation by curcumin, a herbal product. Out of 6 groups of rats, 2 groups received two different doses of carbofuran, that is, 15 and 30% of LD50, respectively, for 30 days. Out of these, 2 groups receiving same doses of carbofuran were pretreated with curcumin (100 mg/kg body weight). The levels of antioxidants, TBARS, GSH, SOD, catalase, and GST were determined in rat brain stem. The 2 remaining groups served as placebo and curcumin treated, respectively. The data suggested that carbofuran at different doses caused significant alterations in the levels of TBARS and GSH in dose dependent manner. The TBARS and GSH contents were elevated. The activities of SOD, catalase, and GST were significantly inhibited at both doses of carbofuran. The ratio of P/A was also found to be sharply increased. The pretreatment of curcumin exhibited significant protection from carbofuran induced toxicity. The results suggested that carbofuran at sublethal doses was able to induce oxidative stress in rat brain which could be attenuated by curcumin. PMID:27213055

  3. Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats.

    PubMed

    Boyko, Matthew; Nassar, Ahmad; Kaplanski, Jacob; Zlotnik, Alexander; Sharon-Granit, Yael; Azab, Abed N

    2015-01-01

    Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO). Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL-) 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

  4. Nicotinamide Inhibits Alkylating Agent-Induced Apoptotic Neurodegeneration in the Developing Rat Brain

    PubMed Central

    Naseer, Muhammad Imran; Ullah, Ikram; Suh, Joo Won; Kim, Myeong Ok

    2011-01-01

    Background Exposure to the chemotherapeutic alkylating agent thiotepa during brain development leads to neurological complications arising from neurodegeneration and irreversible damage to the developing central nerve system (CNS). Administration of single dose of thiotepa in 7-d postnatal (P7) rat triggers activation of apoptotic cascade and widespread neuronal death. The present study was aimed to elucidate whether nicotinamide may prevent thiotepa-induced neurodegeneration in the developing rat brain. Methodology/Principal Findings Neuronal cell death induced by thiotepa was associated with the induction of Bax, release of cytochrome-c from mitochondria into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1). Post-treatment of developing rats with nicotinamide suppressed thiotepa-induced upregulation of Bax, reduced cytochrome-c release into the cytosol and reduced expression of activated caspase-3 and cleavage of PARP-1. Cresyl violet staining showed numerous dead cells in the cortex hippocampus and thalamus; post-treatment with nicotinamide reduced the number of dead cells in these brain regions. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) and immunohistochemical analysis of caspase-3 show that thiotepa-induced cell death is apoptotic and that it is inhibited by nicotinamide treatment. Conclusion Nicotinamide (Nic) treatment with thiotepa significantly improved neuronal survival and alleviated neuronal cell death in the developing rat. These data demonstrate that nicotinamide shows promise as a therapeutic and neuroprotective agent for the treatment of neurodegenerative disorders in newborns and infants. PMID:22164206

  5. A multidimensional magnetic resonance histology atlas of the Wistar rat brain.

    PubMed

    Johnson, G Allan; Calabrese, Evan; Badea, Alexandra; Paxinos, George; Watson, Charles

    2012-09-01

    We have produced a multidimensional atlas of the adult Wistar rat brain based on magnetic resonance histology (MRH). This MR atlas has been carefully aligned with the widely used Paxinos-Watson atlas based on optical sections to allow comparisons between histochemical and immuno-marker data, and the use of the Paxinos-Watson abbreviation set. Our MR atlas attempts to make a seamless connection with the advantageous features of the Paxinos-Watson atlas, and to extend the utility of the data through the unique capabilities of MR histology: a) ability to view the brain in the skull with limited distortion from shrinkage or sectioning; b) isotropic spatial resolution, which permits sectioning along any arbitrary axis without loss of detail; c) three-dimensional (3D) images preserving spatial relationships; and d) widely varied contrast dependent on the unique properties of water protons. 3D diffusion tensor images (DTI) at what we believe to be the highest resolution ever attained in the rat provide unique insight into white matter structures and connectivity. The 3D isotropic data allow registration of multiple data sets into a common reference space to provide average atlases not possible with conventional histology. The resulting multidimensional atlas that combines Paxinos-Watson with multidimensional MRH images from multiple specimens provides a new, comprehensive view of the neuroanatomy of the rat and offers a collaborative platform for future rat brain studies.

  6. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats.

    PubMed

    Jiang, Y; Wei, N; Lu, T; Zhu, J; Xu, G; Liu, X

    2011-01-13

    Inflammation plays a vital role in the pathogenesis of ischemic stroke. Brain-derived neurotrophic factor (BDNF) may protect brain tissues from ischemic injury. In this study, we investigated whether intranasal BDNF exerted neuroprotection against ischemic insult by modulating the local inflammation in rats with ischemic stroke. Rats were subjected to temporary occlusion of the right middle cerebral artery (120 min) and intranasal BDNF or vehicle was adminstrated 2 h after reperfusion. Infarct volume and neuron injury were measured using triphenyltetrazolium chloride, Nissl staining and TUNEL assay, respectively. Microglia were detected by immunohistofluorescence. Tumor necrosis factor-α, interleukin10 and mRNAs were evaluated by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. DNA-binding activity of nuclear factor-kappa B was measured by electrophoretic mobility shift assay. BDNF level in brain tissues was markedly raised following intranasal administration. There were more Nissl positive and less TUNEL positive neurons in BDNF group than in control group while intranasal BDNF did not reduce the infarct volume significantly (n=6, 0.27±0.04 vs. 0.24±0.05, P>0.05). BDNF increased the number of activated microglia (OX-42 positive) and phagocytotic microglia (ED1 positive). BDNF suppressed tumor necrosis factor-α and mRNA expression while increasing the interleukin10 and mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B (n=6, 49.78±1.23 vs. 52.89±1.64, P<0.05). Our data suggest intranasal BDNF might protect the brain against ischemic insult by modulating local inflammation via regulation of the levels of cellular, cytokine and transcription factor in the experimental stroke.

  7. The effect of diet on the fatty acid compositions of serum, brain, brain mitochondria and myelin in the rat

    PubMed Central

    Rathbone, L.

    1965-01-01

    1. Three groups of female rats (8–12 weeks old) were maintained respectively on a linoleic acid-rich diet, a linoleic acid-poor predominantly saturated-fatty acid diet and a normal diet. Changes in the fatty acid compositions of serum, brain, brain mitochondria-rich fraction and myelin were observed. 2. Of the serum fatty acids, linoleic acid showed the greatest change in the percentage of the total acids in response to diet; the change in the proportion of oleic acid was considerable. The percentages of arachidonic acid in serum fatty acids in the groups on the linoleic acid-rich and linoleic acid-poor diets were similar, but higher than those in the normal group. 3. Changes in the proportions of linoleic acid, arachidonic acid and docosahexaenoic acid occurred in brain fatty acids that to some extent paralleled those occurring in the serum. Changes in the proportions of most other acids in the serum fatty acids were not accompanied by corresponding changes in the brain fatty acids. 4. The percentage fatty acid compositions of a mitochondria-rich fraction and myelin are given, and changes in the relative proportions of linoleic acid, arachidonic acid and possibly some docosapolyenoic acids were demonstrated to occur as a result of diet. 5. The results are discussed in relation to the possible aetiology of multiple sclerosis. PMID:5881652

  8. Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor.

    PubMed

    Shaw, Tapan Kumar; Mandal, Dipika; Dey, Goutam; Pal, Murari Mohan; Paul, Paramita; Chakraborty, Samrat; Ali, Kazi Asraf; Mukherjee, Biswajit; Bandyopadhyay, Amal Kumar; Mandal, Mahitosh

    2017-11-01

    Docetaxel (DTX) is found to be very effective against glioma cell in vitro. However, in vivo passage of DTX through BBB is extremely difficult due to the physicochemical and pharmacological characteristics of the drug. No existing formulation is successful in this aspect. Hence, in this study, effort was made to send DTX through blood-brain barrier (BBB) to brain to treat diseases such as solid tumor of brain (glioma) by developing DTX-loaded nanoliposomes. Primarily drug-excipients interaction was evaluated by FTIR spectroscopy. The DTX-loaded nanoliposomes (L-DTX) were prepared by lipid layer hydration technique and characterized physicochemically. In vitro cellular uptake in C6 glioma cells was investigated. FTIR data show that the selected drug and excipients were chemically compatible. The unilamellar vesicle size was less than 50 nm with smooth surface. Drug released slowly from L-DTX in vitro in a sustained manner. The pharmacokinetic data shows more extended action of DTX from L-DTX in experimental rats than the free-drug and Taxotere®. DTX from L-DTX enhanced 100% drug concentration in brain as compared with Taxotere® in 4 h. Thus, nanoliposomes as vehicle may be an encouraging strategy to treat glioma with DTX.

  9. Labile iron pool and ferritin content in developing rat brain gamma-irradiated in utero.

    PubMed

    Robello, Elizabeth; Galatro, Andrea; Puntarulo, Susana

    2009-05-01

    This study was aimed to assess the content of total Fe, Ferritin (Ft) and labile Fe pool (LIP) in developing rat brain exposed in utero to 1 Gy of gamma-irradiation. A significant increase (2.3-fold) in the total Fe content of the fetal rat brain irradiated in utero was observed from 1 to 4h post-irradiation, as compared to the content in non-irradiated brain. Ft was analyzed by immunoblotting. The Ft protein was composed by 20 kDa subunits. According to the analysis of the band density in the Western blot, the Ft content decreased by 77+/-15% 2h after gamma-irradiation, as compared to the values in non-irradiated samples. The effect of gamma-irradiation on the LIP was studied by both electron paramagnetic resonance (EPR) and by a fluorescence technique employing calcein (CA). A reduction on the LIP was detected at 2h post-irradiation, independently of the methodology employed for the assay. Since NO content increased in the same time frame of LIP decreasing, a protective role for NO is suggested in fetal rat brain exposed to gamma-irradiation. The data presented in this work are the first experimental evidence suggesting that, as part of the network of the cellular response to limit irradiation-dependent injury, a complex interaction between Fe and NO could be triggered.

  10. Wearable 3-D Photoacoustic Tomography for Functional Brain Imaging in Behaving Rats

    PubMed Central

    Tang, Jianbo; Coleman, Jason E.; Dai, Xianjin; Jiang, Huabei

    2016-01-01

    Understanding the relationship between brain function and behavior remains a major challenge in neuroscience. Photoacoustic tomography (PAT) is an emerging technique that allows for noninvasive in vivo brain imaging at micrometer-millisecond spatiotemporal resolution. In this article, a novel, miniaturized 3D wearable PAT (3D-wPAT) technique is described for brain imaging in behaving rats. 3D-wPAT has three layers of fully functional acoustic transducer arrays. Phantom imaging experiments revealed that the in-plane X-Y spatial resolutions were ~200 μm for each acoustic detection layer. The functional imaging capacity of 3D-wPAT was demonstrated by mapping the cerebral oxygen saturation via multi-wavelength irradiation in behaving hyperoxic rats. In addition, we demonstrated that 3D-wPAT could be used for monitoring sensory stimulus-evoked responses in behaving rats by measuring hemodynamic responses in the primary visual cortex during visual stimulation. Together, these results show the potential of 3D-wPAT for brain study in behaving rodents. PMID:27146026

  11. Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

    PubMed Central

    Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

    2012-01-01

    AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

  12. Protein and DNA oxidation in different anatomic regions of rat brain in a mimetic ageing model.

    PubMed

    Yanar, Karolin; Aydın, Seval; Cakatay, Ufuk; Mengi, Murat; Buyukpınarbaşılı, Nur; Atukeren, Pınar; Sitar, Mustafa E; Sönmez, Aslı; Uslu, Ezel

    2011-12-01

    It has been reported that d-galactose administration causes an increase in oxidative and osmotic stresses in several tissues of rodents. In this study, we established a brain ageing model by using d-galactose and investigated the concentrations of oxidative stress markers on the hippocampus, parietal and frontal lobes of male Sprague-Dawley rats. A mimetic ageing model was established by injecting d-galactose (60 mg/kg/day/i.p.) in the experimental group for 42 days. At the end of this period, we tested spatial memory using the Morris water maze test. To investigate the magnitude of oxidative damage in proteins, lipids and DNA, we studied the concentrations of various oxidative stress parameters in the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell oxidative damage was observed in each of the three anatomic regions. It was found that protein carbonyl groups and advanced oxidation product concentrations in the d-galactose applied group were significantly high in each of the three brain lobes compared with the control group. Thiol concentration was found to be decreased in the parietal lobe. A concurrent increase in lipid hydroperoxides was also observed in this lobe. On the other hand, 8-hydroxy-2'-deoxyguanosine concentration was significantly increased in the hippocampal lobe of rats in the experimental group when compared with the controls. The results obtained from the mimetic ageing model rats showed that various anatomical regions of brain have different susceptibility to oxidative damage of proteins, lipids and DNA.

  13. Immunocytochemical localization of TASK-3 protein (K2P9.1) in the rat brain.

    PubMed

    Marinc, Christiane; Derst, Christian; Prüss, Harald; Veh, Rüdiger W

    2014-01-01

    Among all K2P channels, TASK-3 shows the most widespread expression in rat brain, regulating neuronal excitability and transmitter release. Using a recently purified and characterized polyclonal monospecific antibody against TASK-3, the entire rat brain was immunocytochemically analyzed for expression of TASK-3 protein. Besides its well-known strong expression in motoneurons and monoaminergic and cholinergic neurons, TASK-3 expression was found in most neurons throughout the brain. However, it was not detected in certain neuronal populations, and neuropil staining was restricted to few areas. Also, it was absent in adult glial cells. In hypothalamic areas, TASK-3 was particularly strongly expressed in the supraoptic and suprachiasmatic nuclei, whereas other hypothalamic nuclei showed lower protein levels. Immunostaining of hippocampal CA1 and CA3 pyramidal neurons showed strongest expression, together with clear staining of CA3 mossy fibers and marked staining also in the dentate gyrus granule cells. In neocortical areas, most neurons expressed TASK-3 with a somatodendritic localization, most obvious in layer V pyramidal neurons. In the cerebellum, TASK-3 protein was found mainly in neurons and neuropil of the granular cell layer, whereas Purkinje cells were only faintly positive. Particularly weak expression was demonstrated in the forebrain. This report provides a comprehensive overview of TASK-3 protein expression in the rat brain.

  14. Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study.

    PubMed

    Abramovitch, Rinat; Itzik, Anna; Harel, Hila; Nagler, Arnon; Vlodavsky, Israel; Siegal, Tali

    2004-01-01

    Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF) is a potent inhibitor of collagen type alpha1(I). In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI), we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001). Treatment with HF significantly prolonged survival of treated animals (142%; P = .001). In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05). Additionally, HF treatment inhibited vessel maturation (P = .03). Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  15. Sodium valproate exposure during the brain growth spurt transiently impairs spatial learning in prepubertal rats

    PubMed Central

    Filgueiras, Cláudio C.; Pohl-Guimarães, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

    2012-01-01

    The brain is extremely vulnerable to teratogenic insults during the brain growth spurt, a period that starts during the third trimester of human gestation and is characterized by synaptogenesis establishment of neuronal circuits. While the treatment of epilepsy during pregnancy increases the risk of neurodevelopmental disorders in offspring, the consequences of exposure to anticonvulsants during the brain growth spurt remain poorly known. Here we investigate whether exposure to sodium valproate (VPA) during a similar period in rats impairs spatial learning of juvenile rats. Long-Evans rats were exposed to VPA (200mg/kg) or saline solution (SAL) every other day between postnatal day (PN) 4 and PN10. At PN23 and PN30, Morris water maze performance was evaluated during 6 consecutive days. In the group of animals which started their tests at PN23, the VPA exposure impaired both, swimming speed and learning/memory performance. Interestingly, no differences were observed between VPA and control animals tested from PN30 to PN35. Our data suggests that the neurobehavioral deficits caused by VPA exposure during the brain growth spurt are transitory. PMID:23178315

  16. MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

    NASA Astrophysics Data System (ADS)

    Hankin, Joseph A.; Farias, Santiago E.; Barkley, Robert M.; Heidenreich, Kim; Frey, Lauren C.; Hamazaki, Kei; Kim, Hee-Yong; Murphy, Robert C.

    2011-06-01

    Matrix-assisted laser desorption ionization/ionization imaging mass spectrometry (MALDI IMS) with a time-of-flight analyzer was used to characterize the distribution of lipid molecular species in the brain of rats in two injury models. Ischemia/reperfusion injury of the rat brain after bilateral occlusion of the carotid artery altered appearance of the phospholipids present in the hippocampal region, specifically the CA1 region. These brain regions also had a large increase in the ion abundance at m/z 548.5 and collisional activation supported identification of this ion as arising from ceramide (d18:1/18:0), a lipid known to be associated with cellular apoptosis. Traumatic brain injury model in the rat was examined by MALDI IMS and the area of damage also showed an increase in ceramide (d18:1/18:0) and a remarkable loss of signal for the potassium adduct of the most abundant phosphocholine molecular species 16:0/18:1 (PC) with a corresponding increase in the sodium adduct ion. This change in PC alkali attachment ion was suggested to be a result of edema and influx of extracellular fluid likely through a loss of Na/K-ATPase caused by the injury. These studies reveal the value of MALDI IMS to examine tissues for changes in lipid biochemistry and will provide data needed to eventually understand the biochemical mechanisms relevant to tissue injury.

  17. Characterization of angiotensin-binding sites in the bovine adrenal and the rat brain

    SciTech Connect

    Rogulja, I.

    1989-01-01

    The first study was designed to determine whether systemically administered MSG affects neurons in the CVOs that are potentially important in mediating angiotensin-dependent responses. Rats were pretreated with MSG and the receptors for angiotensin II were assayed by radioligand binding in brain homogenates from the septum anteroventral third ventricular region (AV3V) and the thalamus/hypothalamus region using {sup 125}I-angiotensin II as the radioligand. The results of this experiment indicate that systematically administered MSG in the rat significantly reduced the number (Bmax) of Ang II receptors in a tissue sample which contained both extra blood-brain barrier organs as well as tissue within the blood-brain barrier with no change in the affinity (Kd) of the binding sites. The second chapter reports the successful solubilization of bovine adrenal {sup 125}I Ang II and {sup 125}I Sar{sup 1},Ile{sup 8}-Ang II binding sites with the detergent CHAPS. The results of our studies indicate the presence of two angiotensin binding sites. The one site is specific for naturally occurring angiotensins as well as sarcosine-1 substituted angiotensin analogues. The other site which can be optimally stabilized be re-addition of 0.3% CHAPS into the incubation assay binds sarcosine-1 substituted angiotensins exclusively. Hydrophobic interaction chromatography experiments suggest that these sites, possibly, represent distinct proteins. The third chapter discusses the successful solubilization and partial characterization of the rat brain angiotensin receptor.

  18. Transcranial MRI-guided FUS-induced BBB opening in the rat brain

    NASA Astrophysics Data System (ADS)

    Treat, Lisa H.; McDannold, Nathan J.; Hynynen, Kullervo

    2004-05-01

    The blood-brain barrier (BBB) has been a major limitation in treating diseases of the brain because therapeutic agents are either unable to penetrate or have dose-limiting side effects in diffuse opening of the BBB. A previous study demonstrated that focused ultrasound (FUS) can locally open the BBB in a rabbit model when a piece of skull is removed and that magnetic resonance imaging (MRI) can be used to guide and monitor the procedure. This study examined whether the same desired effect of local BBB disruption can be achieved by applying FUS through an intact skull in a rat model. Twenty-eight Sprague-Dawley rats were anesthetized, shaved, and sonicated at four focal locations in the brain, using a 1.5-MHz focused transducer. Contrast-enhanced MR images were obtained before and after sonication. The images indicated contrast agent penetration at the focal coordinates following Optison-enhanced sonication. This study demonstrated that the distortion of the ultrasound beam by the rat skull was not significant enough to inhibit focal BBB opening. Subsequent experiments using MRI-guided FUS to aid in targeted drug delivery to brain tumors in a rodent model could thus be performed more efficiently without cranial surgery. [Research funded by NIH Grant No. CA76550.

  19. Near-infrared oxymeter prototype for noninvasive analysis of rat brain oxygenation

    NASA Astrophysics Data System (ADS)

    Crespi, Francesco; Donini, Maurizio; Bandera, Andrea; Heidbreder, Christian; Salvatori, Giorgia; Rovati, Luigi

    2004-09-01

    The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivo methodologies i.e. invasiveness. Optic fibre probes were used as optical head of a novel, highly sensitive near infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of anaesthetised adult rat's head, without any surgery. Then pharmacological treatments with saline (300μl s.c.) amphetamine (2mg/kg) or nicotine (0.4mg/kg) were performed. Within 10-20 min amphetamine substantially increased HbO2 and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease of HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2 and Hb levels in the rat brain, markers of the degree of tissue oxygenation, index of blood level then of the state of brain metabolism.

  20. [Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

    PubMed

    Tezikov, E B; Litvicki, P F

    2015-01-01

    On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

  1. Minor Functional Deficits in Basic Response Patterns for Reinforcement after Frontal Traumatic Brain Injury in Rats.

    PubMed

    Vonder Haar, Cole; Winstanley, Catharine A

    2016-10-15

    Traumatic brain injury (TBI) is a major contributor to numerous psychiatric conditions and chronic behavioral dysfunction. Recent studies in experimental brain injury have begun to adopt operant methodologies to assess these deficits, all of which rely on the process of reinforcement. No studies have directly examined how reinforced behaviors are affected by TBI, however. The current study assessed performance under the four most common schedules of reinforcement (fixed ratio, variable ratio, fixed interval, variable interval) and one higher order schedule assessing motivation (progressive ratio) after bilateral, pre-frontal controlled cortical impact injury. TBI-induced differences on the basic schedules were minor, with the exception of the variable ratio, where increased efficacy (more reinforcers, higher response rates, lower interresponse times) at higher requirements was observed as a result of brain injury. Performance on the progressive ratio schedule showed some gross differences between the groups, in that sham rats became more efficient under this schedule while injured rats perseverated in lever pressing. Further, injured rats were specifically impaired at lower response requirements on the progressive ratio. Taken together, these findings indicate that simple reinforced behaviors are mostly unaffected after TBI, except in the case of variable ratio schedules, but the altered performance on the higher-order progressive ratio schedule suggests changes involving motivation or potentially perseveration. These findings validate operant measures of more complex behaviors for brain injury, all of which rely on reinforcement and can be taken into consideration when adapting and developing novel functional assessments.

  2. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    NASA Technical Reports Server (NTRS)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  3. Tenoxicam modulates antioxidant redox system and lipid peroxidation in rat brain.

    PubMed

    Naziroğlu, Mustafa; Uğuz, Abdulhadi Cihangir; Gokçimen, Alpaslan; Bülbül, Metin; Karatopuk, Dilek Ulusoy; Türker, Yasin; Cerçi, Celal

    2008-09-01

    We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and beta-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system.

  4. Effects of long-term treatment with methyl mercury on the developing rat brain

    SciTech Connect

    Lindstroem, H.; Luthman, J.; Olson, L. ); Oskarsson, A.; Sundberg, J. )

    1991-12-01

    Sprague-Dawley rats were exposed to low doses of methyl mercury (3.9 mg mercury/kg diet), via their dams during gestation and lactation and directly via their diet until sacrifice at 50 days postpartum, in order to study possible detrimental effects on CNS development. The methyl mercury exposure of the rats resulted in a brain concentration of 1.45 {plus minus} 0.06 mg mercury/kg wet weight (mean {plus minus} SEM). No general toxic effects were observed; body weight was not affected, brain weight was only slightly increased. No discernible general morphological alterations were seen in the brain as evaluated using cresyl violet histology. Furthermore, no effects on GFA-positive astrocytes in brain sections were observed and computerized morphometry of smeared astrocytes from frontal cortex, hippocampus, and cerebellum did not reveal any effects of the methyl mercury treatment. The noradrenaline (NA) and dopamine (DA) systems were also studied. In cerebellum the NA levels were increased whereas in other regions analyzed NA and DA levels were unchanged. Thus, long-term low-dosage exposure of methyl mercury in rats during development does not appear to exert any major effects on the morphological maturation of neurons and astrocytes. However, the results indicate the effects may occur in specific transmitter-identified systems, such as the NA input to cerebellum.

  5. Wearable 3-D Photoacoustic Tomography for Functional Brain Imaging in Behaving Rats.

    PubMed

    Tang, Jianbo; Coleman, Jason E; Dai, Xianjin; Jiang, Huabei

    2016-05-05

    Understanding the relationship between brain function and behavior remains a major challenge in neuroscience. Photoacoustic tomography (PAT) is an emerging technique that allows for noninvasive in vivo brain imaging at micrometer-millisecond spatiotemporal resolution. In this article, a novel, miniaturized 3D wearable PAT (3D-wPAT) technique is described for brain imaging in behaving rats. 3D-wPAT has three layers of fully functional acoustic transducer arrays. Phantom imaging experiments revealed that the in-plane X-Y spatial resolutions were ~200 μm for each acoustic detection layer. The functional imaging capacity of 3D-wPAT was demonstrated by mapping the cerebral oxygen saturation via multi-wavelength irradiation in behaving hyperoxic rats. In addition, we demonstrated that 3D-wPAT could be used for monitoring sensory stimulus-evoked responses in behaving rats by measuring hemodynamic responses in the primary visual cortex during visual stimulation. Together, these results show the potential of 3D-wPAT for brain study in behaving rodents.

  6. The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury.

    PubMed

    Yang, Yang; Zhang, Yong-Gang; Lin, Guo-An; Xie, He-Qiu; Pan, Hai-Tao; Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

    2014-03-20

    The protective effects of hyperbaric oxygenation following traumatic brain injury have been widely investigated; however, few studies have made systematic comparisons between the different hyperbaric oxygenation manipulations and their corresponding effects. In this study, male Sprague-Dawley rats were observed at 4h, 15d and 75d after traumatic brain injury. The effects of the different hyperbaric oxygenation manipulations on the rats were compared based on morphological, molecular biological and behavioral tests. Our results showed that hyperbaric oxygenation inhibited cell apoptosis in the rat hippocampus and improved their physiological functions. The effects observed in the hyperbaric oxygen-early group were better than the hyperbaric oxygen-delayed group, and the hyperbaric oxygen-early-delayed group demonstrated the best effects among all the groups. Our results showed the hyperbaric oxygenation was recommended early and delayed post-traumatic brain injury and exposure to hyperbaric oxygenation should be prolonged. These findings provide new ideal therapeutic insight for the clinical treatment of traumatic brain injury.

  7. Agonist and antagonist binding to rat brain muscarinic receptors: influence of aging

    SciTech Connect

    Gurwitz, D.; Egozi, Y.; Henis, Y.I.; Kloog, Y.; Sokolovsky, M.

    1987-03-01

    The objective of the present study was to determine the binding properties of muscarinic receptors in six brain regions in mature and old rats of both sexes by employing direct binding of (/sup 3/H)-antagonist as well as of the labeled natural neurotransmitter, (/sup 3/H)-acetylcholine (( /sup 3/H)-AcCh). In addition, age-related factors were evaluated in the modulation processes involved in agonist binding. The results indicate that as the rat ages the density of the muscarinic receptors is altered differently in the various brain regions: it is decreased in the cerebral cortex, hippocampus, striatum and olfactory bulb of both male and female rats, but is increased (58%) in the brain stem of senescent males while no significant change is observed for females. The use of the highly sensitive technique measuring direct binding of (/sup 3/H)-AcCh facilitated the separate detection of age-related changes in the two classes (high- and low-affinity) of muscarinic agonist binding sites. In old female rats the density of high-affinity (/sup 3/H)-AcCh binding sites was preserved in all tissues studied, indicating that the decreases in muscarinic receptor density observed with (/sup 3/H)-antagonist represent a loss of low-affinity agonist binding sites. In contrast, (/sup 3/H)-AcCh binding is decreased in the hypothalamus and increased in the brain stem of old male rats. These data imply sexual dimorphism of the aging process in central cholinergic mechanisms.

  8. Brain Uptake of the Drug of Abuse γ-Hydroxybutyric Acid in Rats

    PubMed Central

    Roiko, Samuel A.; Felmlee, Melanie A.

    2012-01-01

    γ-Hydroxybutyric acid (GHB) is an endogenous compound and a substrate for the ubiquitous monocarboxylate transporter (MCT) family. GHB is also a drug of abuse due to its sedative/hypnotic and euphoric effects, with overdoses resulting in toxicity and death. The goal of this study was to characterize the distribution of GHB into the brain using in vivo microdialysis and in vitro uptake studies and to determine concentration-effect relationships for GHB in a rat animal model. GHB was administered to rats (400, 600, and 800 mg/kg i.v.), and blood, dialysate, and urine were collected for 6 h post-GHB administration. The GHB plasma and extracellular fluid (ECF) concentration-time profiles revealed that GHB concentrations in ECF closely followed plasma GHB concentrations. Sleep time increased in a dose-dependent manner (91 ± 18, 134 ± 11, and 168 ± 13 min, for GHB 400, 600, and 800 mg/kg, respectively). GHB partitioning into brain ECF was not significantly different at 400, 600, and 800 mg/kg. GHB uptake in rat and human brain endothelial cells exhibited concentration dependence. The concentration-dependent uptake of GHB at pH 7.4 was best-fit to a single-transporter model [Km = 18.1 mM (human), 23.3 mM (rat), Vmax = 248 and 258 pmol · mg−1 · min−1 for human and rat, respectively]. These findings indicate that although GHB distribution into the brain is mediated via MCT transporters, it is not capacity-limited over the range of doses studied in this investigation. PMID:22019629

  9. Sodium tungstate attenuate oxidative stress in brain tissue of streptozotocin-induced diabetic rats.

    PubMed

    Nakhaee, Alireza; Bokaeian, Mohammad; Akbarzadeh, Azim; Hashemi, Mohammad

    2010-08-01

    High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.

  10. Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate.

    PubMed

    Ram, Z; Samid, D; Walbridge, S; Oshiro, E M; Viola, J J; Tao-Cheng, J H; Shack, S; Thibault, A; Myers, C E; Oldfield, E H

    1994-06-01

    Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.

  11. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    PubMed

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  12. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    PubMed

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation.

  13. Expression of brain-derived neurotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats.

    PubMed

    Truettner, J; Schmidt-Kastner, R; Busto, R; Alonso, O F; Loor, J Y; Dietrich, W D; Ginsberg, M D

    1999-06-01

    Traumatic brain injury can induce the expression of stress-related and neurotrophic genes both within the injury site and in distant regions. These genes may affect severity of damage and/or be neuroprotective. We used in situ hybridization to assess the alterations in expression of the heat shock protein HSP70, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) genes in rat brain following moderate fluid-percussion (F-P) injury at various survival times. HSP70 gene expression was induced at and surrounding the injury site as early as 30 min after trauma. This elevated signal spread ventrally and laterally through the ipsilateral cortex and into the underlying white matter over the next few hours. In addition, there was elevated expression in the temporal hippocampus. BDNF was strongly upregulated in the granular cells of the dentate gyrus and in the CA3 hippocampus 2-6 h after injury. Cortical regions at and near the injury site showed no response at the mRNA level. NGF mRNA increased over the granular cells of the dentate gyrus at early time points. There was also a weaker secondary induction of the NGF gene in the contralateral dentate gyrus of some animals. Cortical response was observed in the entorhinal cortex, bilaterally, but not at the injury site. All three of the studied genes responded quickly to injury, as early as 30 min. The induction of gene expression for neurotrophins in regions remote from areas with histopathology may reflect coupling of gene expression to neuronal excitation, which may be associated with neuroprotection and plasticity.

  14. In vivo and in vitro effects of fructose on rat brain acetylcholinesterase activity: an ontogenetic study.

    PubMed

    Guimarães, Carine A; Biella, Mairis S; Lopes, Abigail; Deroza, Pedro F; Oliveira, Mariana B; Macan, Tamires P; Streck, Emilio L; Ferreira, Gustavo C; Zugno, Alexandra I; Schuck, Patrícia F

    2014-12-01

    Increased fructose concentrations are the biochemical hallmark of fructosemia, a group of inherited disorders on the metabolic pathway of this sugar. The main clinical findings observed in patients affected by fructosemia include neurological abnormalities with developmental delay, whose pathophysiology is still undefined. In the present work we investigated the in vitro and in vivo effects of fructose on acetylcholinesterase (AchE) activity in brain structures of developing rats. For the in vitro experiments, fructose was added at increasing concentrations to the incubation medium. It was observed that fructose provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30-day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments, rats were killed 1 h after a single fructose administration (5 µmol/g). Control group received the same volume of saline solution. We found that AchE activity was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose administration. Finally, we observed that AchE activity was unaffected by acute fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90-day-old rats. The present data suggest that a disruption in cholinergic homeostasis may be involved in the pathophysiology of brain damage observed in young patients affected by fructosemia.

  15. Brain beta-adrenergic receptor binding in rats with obesity induced by a beef tallow diet.

    PubMed

    Matsuo, T; Suzuki, M

    1997-01-01

    We have previously reported that compared with safflower oil diet, feeding a beef tallow diet leads to a greater accumulation of body fat by reducing sympathetic activities. The present study examined the effects of dietary fats consisting of different fatty acids on alpha1- and beta-adrenergic receptor binding in the hypothalamus and cerebral cortex. Male Sprague-Dawley rats were meal-fed isoenergetic diets based on safflower oil (rich in n-6 polyunsaturated fatty acids) or beef tallow (rich in saturated fatty acids) for 8 weeks. Binding affinities of the beta-adrenergic receptor in the hypothalamus and cortex were significantly lower in the beef tallow diet group, but those of the alpha1-receptor did not differ between the two groups. The polyunsaturated to saturated fatty acid (P/S) ratio and fluidities of plasma membranes in the hypothalamus and cortex were lower in the beef tallow diet group than in the safflower oil diet group. These results suggest that the beef tallow diet decreases membrane fluidity by altering the fatty acid composition of plasma membranes in the hypothalamus and cerebral cortex of rat. Consequently, beta-adrenergic receptor binding affinities in the brain were lower in rats fed the beef tallow diet than in rats fed the safflower oil diet. We recognized that there is possible link between the membrane fluidity and the changes in affinity of beta-adrenoceptors in rat brain.

  16. Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats.

    PubMed

    Attella, M J; Hoffman, S W; Stasio, M J; Stein, D G

    1989-07-01

    Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed-spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury.

  17. Expression of the 5-HT receptors in rat brain during memory consolidation.

    PubMed

    Meneses, A; Manuel-Apolinar, L; Rocha, L; Castillo, E; Castillo, C

    2004-07-09

    Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using 3H 5-HT as ligand, 2 nM, specific activity 123 Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.

  18. Basal and learning task-related brain oxidative metabolism in cirrhotic rats.

    PubMed

    Méndez, Marta; Méndez-López, Magdalena; López, Laudino; Aller, María Angeles; Arias, Jaime; Arias, Jorge L

    2009-03-16

    Hepatic encephalopathy is a neurological complication observed in patients with liver disease. Subjects with hepatic encephalopathy can develop memory alterations. In order to investigate brain oxidative metabolism in an animal model of chronic cirrhosis and its modification after spatial working memory task, we determined the neural metabolic activity of several brain limbic system regions by cytochrome oxidase (COx) histochemistry and assessed the spatial working memory in the Morris water maze of rats with cirrhosis by administration of thioacetamide. This COx histochemistry was done in cirrhotic and control rats under basal conditions and after the spatial working memory task. The histochemical results showed differences in basal COx activity between control and cirrhotic rats in hippocampal and thalamic regions. In cirrhotic rats basal COx activity was increased in the CA1 and CA3 areas of the hippocampus and reduced in the anterodorsal and anteroventral thalamic nuclei. We found impaired spatial working memory in animals with cirrhosis. These animals showed absence of metabolic activation of the CA3 hippocampal subfield and the lateral mammillary nucleus and disturbance of COx activity in the medial mammillary nucleus and the anteroventral thalamus. These findings suggest that cirrhotic rats show spatial working memory deficits that could be related to the alteration of metabolic activity of neural regions thought to be involved in the processing of spatial memories.

  19. Brain orexins and wake regulation in rats exposed to maternal deprivation.

    PubMed

    Feng, Pingfu; Vurbic, Drina; Wu, Zhenzhen; Strohl, Kingman P

    2007-06-18

    Maternal deprivation (MD) is a neonatal stressor that leads to behavioral and molecular manifestations of chronic stress in adulthood. Recent evidence has suggested that stress may impact wake regulation through corticotropin-releasing hormone (CRH) and the orexinergic system. We studied the wake/sleep features and brain levels of orexin and orexin receptors in adult rats neonatally subjected to either ten days of MD or a control procedure from postnatal day 4. At 3 months of age, one set of rats from both groups underwent 48 h of polysomnographic recording. All rats (including those that did not undergo surgery) were subsequently sacrificed for ELISA, radioimmunoassay and western blot measurement of orexins, orexin receptors and CRH in multiple brain regions. Neonatal MD induced an increase of total wake time (decreased total sleep) during the light period, which corresponds to human night time. This increase was specifically composed of quiet wake, while a small but significant decrease of active wake was observed during the dark period. At the molecular level, MD led to increased hypothalamic CRH and orexin A, and frontal cortical orexin 1 receptors (OX1R). However, hippocampal orexin B was reduced in the MD group. Our study discovered for the first time that the adult MD rat has sleep and neurobiological features of hyperarousal, which is typical in human insomnia. We concluded that neonatal MD produces adult hyperarousal in sleep physiology and neurobiology, and that the adult MD rat could be a model of insomnia with an orexinergic mechanism.

  20. Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain.

    PubMed

    Ya, Bai-liu; Liu, Wen-yan; Ge, Feng; Zhang, Yan-xia; Zhu, Bao-liang; Bai, Bo

    2013-08-01

    Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of lear