Sample records for rat forelimb reduces

  1. Adaptive changes in the motor cortex during and after longterm forelimb immobilization in adult rats

    PubMed Central

    Viaro, Riccardo; Budri, Mirco; Parmiani, Pierantonio; Franchi, Gianfranco

    2014-01-01

    Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization. PMID:24566543

  2. Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Steskal, J.; Johansson, C.; Tipton, C. M.

    1984-01-01

    The tail suspension model (head-down tilt) simulates hypogravity in terms of musculoskeletal loss in the rat. However, little is known of tissue fluid shifts and body weight distribution in this model. Tissue fluid pressures were measured by wick catheters in 12 Munich-Wistar rats before, during, and after 48 hrs of tail suspension (about 30 deg head-down tilt). Subcutaneous tissue fluid pressure in the neck increased from -2.2 + or - 0.4 (normal horizontal position) to +4.0 + or - 1.5 cm H2O during tail suspension, indicating a cephalic fluid shift and significant edema during head-down tilt. In a separate study, six rats were suspended at 30-70 deg, and forelimb load and tail tension were measured by a balance and force transducer, respectively. Approximately 50 percent of body weight (BW) was loaded on forelimbs at a head-down tilt angle of 30 deg and forelimb load declined linearly to 10 percent BW at 70 deg. Furthermore, tail tension increased from 50 percent BW at 30 deg to 85 percent BW at 70 deg. These results indicate that less than normal loads are applied to forelimbs of rats suspended at angles of less than 30 deg and that the tail bears an increasing proportion of the rat's body weight at head-down tilt angles of less than 30 deg.

  3. Spinal pathways involved in the control of forelimb motor function in rats

    Microsoft Academic Search

    Kim D. Anderson; Ardi Gunawan; Oswald Steward

    2007-01-01

    There is increasing interest in developing rodent models for cervical spinal cord injury (SCI) and techniques to assess forelimb motor function. Previously, we demonstrated that in rats, complete unilateral hemisection at cervical level five (C5) permanently eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion [Anderson, K.D., Gunawan, A., Steward,

  4. Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats.

    PubMed

    Gonzalez-Rothi, Elisa Janine; Rombola, Angela M; Rousseau, Celeste A; Mercier, Lynne M; Fitzpatrick, Garrett M; Reier, Paul J; Fuller, David D; Lane, Michael A

    2015-06-15

    Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer - pseudorabies virus - was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

  5. A robotic platform to assess, guide and perturb rat forelimb movements.

    PubMed

    Vigaru, Bogdan C; Lambercy, Olivier; Schubring-Giese, Maximilian; Hosp, Jonas A; Schneider, Melanie; Osei-Atiemo, Clement; Luft, Andreas; Gassert, Roger

    2013-09-01

    Animal models are widely used to explore the mechanisms underlying sensorimotor control and learning. However, current experimental paradigms allow only limited control over task difficulty and cannot provide detailed information on forelimb kinematics and dynamics. Here we propose a novel robotic device for use in motor learning investigations with rats. The compact, highly transparent, three degree-of-freedom manipulandum is capable of rendering nominal forces of 2 N to guide or perturb rat forelimb movements, while providing objective and quantitative assessments of endpoint motor performance in a 50×30 mm(2) planar workspace. Preliminary experiments with six healthy rats show that the animals can be familiarized with the experimental setup and are able to grasp and manipulate the end-effector of the robot. Further, dynamic perturbations and guiding force fields (i.e., haptic tunnels) rendered by the device had significant influence on rat motor behavior (ANOVA, ). This approach opens up new research avenues for future characterizations of motor learning stages, both in healthy and in stroke models. PMID:23335672

  6. The role of vibrissal sensing in forelimb position control during travelling locomotion in the rat (Rattus norvegicus, Rodentia).

    PubMed

    Niederschuh, Sandra J; Witte, Hartmut; Schmidt, Manuela

    2015-02-01

    In the stem lineage of therians, a comprehensive reorganization of limb and body mechanics took place to provide dynamic stability for rapid locomotion in a highly structured environment. At what was probably the same time, mammals developed an active sense of touch in the form of movable mystacial vibrissae. The rhythmic movements of the limbs and vibrissae are controlled by central pattern-generating networks which might interact with each other in sensorimotor control. To test this possible interaction, we studied covariation between the two by investigating speed-dependent adjustments in temporal and spatial parameters of forelimb and vibrissal kinematics in the rat. Furthermore, the possible role of carpal vibrissae in connecting the two oscillating systems was explored. We compared locomotion on continuous and discontinuous substrates in the presence and absence of the mystacial or/and carpal vibrissae across a speed range of 0.2-0.5m/s and found that a close coupling of the kinematics of the two oscillating systems appears to be precluded by their differential dependence on the animal's speed. Speed-related changes in forelimb kinematics mainly occur in temporal parameters, whereas vibrissae change their spatial excursion. However, whisking frequency is always high enough that at least one whisk cycle falls into the swing phase of the limb, which is the maximum critical period for sensing the substrate on which the forepaw will be placed. The influence of tactile cues on forelimb positional control is more subtle than expected. Tactile cues appear to affect the degree of parameter variation but not average parameters or the failure rate of limbs during walking on a perforated treadmill. The carpal vibrissae appear to play a role in sensing the animal's speed by measuring the duration of the stance phase. The absence of this cue significantly reduces speed-related variation in stride frequency and vibrissal protraction. PMID:25547567

  7. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury

    Microsoft Academic Search

    Timothy Schallert; Sheila M Fleming; J. Leigh Leasure; Jennifer L Tillerson; Sondra T Bland

    2000-01-01

    We have reviewed a battery of useful tests for evaluating sensorimotor function and plasticity acutely and chronically in unilateral rat models of central nervous system injury. These tests include forelimb use for weight shifting during vertical exploration in a cylindrical enclosure, an adhesive removal test of sensory function, and forelimb placing. These tests monitor recovery of sensorimotor function independent of

  8. Gap junction blockers attenuate beta oscillations and improve forelimb function in hemiparkinsonian rats.

    PubMed

    Phookan, Sujoy; Sutton, Alexander C; Walling, Ian; Smith, Autumn; O'Connor, Katherine A; Campbell, Joannalee C; Calos, Megan; Yu, Wilson; Pilitsis, Julie G; Brotchie, Jonathan M; Shin, Damian S

    2015-03-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by akinesia, bradykinesia, resting tremors and postural instability. Although various models have been developed to explain basal ganglia (BG) pathophysiology in PD, the recent reports that dominant beta (?) oscillations (12-30Hz) in BG nuclei of PD patients and parkinsonian animals coincide with motor dysfunction has led to an emerging idea that these oscillations may be a characteristic of PD. Due to the recent realization of these oscillations, the cellular and network mechanism(s) that underlie this process remain ill-defined. Here, we postulate that gap junctions (GJs) can contribute to ? oscillations in the BG of hemiparkinsonian rats and inhibiting their activity will disrupt neuronal synchrony, diminish these oscillations and improve motor function. To test this, we injected the GJ blockers carbenoxolone (CBX) or octanol in the right globus pallidus externa (GPe) of anesthetized hemiparkinsonian rats and noted whether subsequent changes in ? oscillatory activity occurred using in vivo electrophysiology. We found that systemic treatment of 200mg/kg CBX attenuated normalized GPe ? oscillatory activity from 6.10±1.29 arbitrary units (A.U.) (pre-CBX) to 2.48±0.87 A.U. (post-CBX) with maximal attenuation occurring 90.0±20.5min after injection. The systemic treatment of octanol (350mg/kg) also decreased ? oscillatory activity in a similar manner to CBX treatment with ? oscillatory activity decreasing from 3.58±0.89 (pre-octanol) to 2.57±1.08 after octanol injection. Next, 1?l CBX (200mg/kg) was directly injected into the GPe of anesthetized hemiparkinsonian rats; 59.2±19.0min after injection, ? oscillations in this BG nucleus decreased from 3.62±1.17 A.U. to 1.67±0.62 A.U. Interestingly, we were able to elicit ? oscillations in the GPe of naive non-parkinsonian rats by increasing GJ activity with 1?l trimethylamine (TMA, 500nM). Finally, we systemically injected CBX (200mg/kg) into hemiparkinsonian rats which attenuated dominant ? oscillations in the right GPe and also improved left forepaw akinesia in the step test. Conversely, direct injection of TMA into the right GPe of naive rats induced contralateral left forelimb akinesia. Overall, our results suggest that GJs contribute to ? oscillations in the GPe of hemiparkinsonian rats. PMID:25622779

  9. Enhancement of bilateral cortical somatosensory evoked potentials to intact forelimb stimulation following thoracic contusion spinal cord injury in rats.

    PubMed

    Bazley, Faith A; Maybhate, Anil; Tan, Chuen Seng; Thakor, Nitish V; Kerr, Candace; All, Angelo H

    2014-09-01

    The adult central nervous system is capable of significant reorganization and adaptation following neurotrauma. After a thoracic contusive spinal cord injury (SCI) neuropathways that innervate the cord below the epicenter of injury are damaged, with minimal prospects for functional recovery. In contrast, pathways above the site of injury remain intact and may undergo adaptive changes in response to injury. We used cortical somatosensory evoked potentials (SSEPs) to evaluate changes in intact forelimb pathways. Rats received a midline contusion SCI, unilateral contusion SCI, or laminectomy with no contusion at the T8 level and were monitored for 28 days post-injury. In the midline injury group, SSEPs recorded from the contralateral forelimb region of the primary somatosensory cortex were 59.7% (CI 34.7%, 84.8%; c(2) = 21.9; dof = 1; p = 2.9 ×10(-6)) greater than the laminectomy group; SSEPs from the ipsilateral somatosensory cortex were 47.6% (CI 18.3%, 77%; c(2) = 10.1; dof = 1; p = 0.001) greater. Activation of the ipsilateral somatosensory cortex was further supported by BOLD-fMRI, which showed increased oxygenation at the ipsilateral hemisphere at day seven post-injury. In the unilateral injury group, ipsilesional side was compared to the contralesional side. SSEPs on day 14 (148%; CI 111%, 185%) and day 21 (137%; CI 110%, 163%) for ipsilesional forelimb stimulation were significantly increased over baseline (100%). SSEPs recorded from the hindlimb sensory cortex upon ipsilesional stimulation were 33.9% (CI 14.3%, 53.4%; c(2) = 11.6; dof = 1; p = 0.0007) greater than contralesional stimulation. Therefore, these results demonstrate the ability of SSEPs to detect significant enhancements in the activation of forelimb sensory pathways following both midline and unilateral contusive SCI at T8. Reorganization of forelimb pathways may occur after thoracic SCI, which SSEPs can monitor to aid the development of future therapies. PMID:24801738

  10. Decoding the rat forelimb movement direction from epidural and intracortical field potentials

    NASA Astrophysics Data System (ADS)

    Slutzky, Marc W.; Jordan, Luke R.; Lindberg, Eric W.; Lindsay, Kevin E.; Miller, Lee E.

    2011-06-01

    Brain-machine interfaces (BMIs) use signals from the brain to control a device such as a computer cursor. Various types of signals have been used as BMI inputs, from single-unit action potentials to scalp potentials. Recently, intermediate-level signals such as subdural field potentials have also shown promise. These different signal types are likely to provide different amounts of information, but we do not yet know what signal types are necessary to enable a particular BMI function, such as identification of reach target location, control of a two-dimensional cursor or the dynamics of limb movement. Here we evaluated the performance of field potentials, measured either intracortically (local field potentials, LFPs) or epidurally (epidural field potential, EFPs), in terms of the ability to decode reach direction. We trained rats to move a joystick with their forepaw to control the motion of a sipper tube to one of the four targets in two dimensions. We decoded the forelimb reach direction from the field potentials using linear discriminant analysis. We achieved a mean accuracy of 69 ± 3% with EFPs and 57 ± 2% with LFPs, both much better than chance. Signal quality remained good up to 13 months after implantation. This suggests that using epidural signals could provide BMI inputs of high quality with less risk to the patient than using intracortical recordings.

  11. Early life versus lifelong oral manganese exposure differently impairs skilled forelimb performance in adult rats

    PubMed Central

    Beaudin, Stephane A.; Nisam, Sean; Smith, Donald R.

    2013-01-01

    Recent studies of children suggest that exposure to elevated manganese (Mn) levels disrupt aspects of motor, cognitive and behavioral functions that are dependent on dopamine brain systems. Although basal ganglia motor functions are well-known targets of adult occupational Mn exposure, the extent of motor function deficits in adults as a result of early life Mn exposure is unknown. Here we used a rodent model early life versus lifelong oral Mn exposure and the Montoya staircase test to determine whether developmental Mn exposure produces long-lasting deficits in sensorimotor performance in adulthood. Long-Evans male neonate rats (n=11/treatment) were exposed daily to oral Mn at levels of 0, 25, or 50 mg Mn/kg/d from postnatal day (PND) 1-21 (early life only), or from PND 1 - throughout life. Staircase testing began at age PND 120 and lasted 1 month to objectively quantify measures of skilled forelimb use in reaching and pellet grasping/retrieval performance. Behavioral reactivity also was rated on each trial. Results revealed that (1) behavioral reactivity scores were significantly greater in the Mn-exposed groups, compared to controls, during the staircase acclimation/training stage, but not the latter testing stages, (2) early life Mn exposure alone caused long-lasting impairments in fine motor control of reaching skills at the higher, but not lower Mn dose, (3) lifelong Mn exposure from drinking water led to widespread impairment in reaching and grasping/retrieval performance in adult rats, with the lower Mn dose group showing the greatest impairment, and (4) lifelong Mn exposure produced similar (higher Mn group) or more severe (lower Mn group) impairments compared to their early life-only Mn exposed counterparts. Collectively, these results substantiate the emerging clinical evidence in children showing associations between environmental Mn exposure and deficits in fine sensorimotor function. They also show that the objective quantification of skilled motor performance using the staircase test can serve as a sensitive measure of early life insults from environmental agents. Supported by NIEHS R01ES018990. PMID:23623961

  12. Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis.

    PubMed

    Jackson, K L; Dayton, R D; Orchard, E A; Ju, S; Ringe, D; Petsko, G A; Maquat, L E; Klein, R L

    2015-01-01

    Nonsense-mediated mRNA decay (NMD) is an RNA surveillance mechanism that requires upframeshift protein 1 (UPF1). This study demonstrates that human UPF1 exerts protective effects in a rat paralysis model based on the amyotrophic lateral sclerosis (ALS)-associated protein, TDP-43 (transactive response DNA-binding protein 43?kDa). An adeno-associated virus vector (AAV9) was used to express TDP-43 throughout the spinal cord of rats, inducing reproducible limb paralysis, to recapitulate the paralysis in ALS. We selected UPF1 for therapeutic testing based on a genetic screen in yeast. The expression of human TDP-43 or human UPF1 in the spinal cord was titrated to less than twofold over the respective endogenous level. AAV9 human mycUPF1 clearly improved overall motor scores in rats also expressing TDP-43. The gene therapy effect of mycUPF1 was specific and reproducible compared with groups receiving either empty vector or green fluorescent protein vector controls. The gene therapy maintained forelimb motor function in rats that would otherwise become quadriplegic. This work helps validate UPF1 as a novel therapeutic for ALS and other TDP-43-related diseases and may implicate UPF1 and NMD involvement in the underlying disease mechanisms. PMID:25354681

  13. Forelimb Locomotor Assessment Scale (FLAS): Novel Assessment of Forelimb Dysfunction After Cervical Spinal Cord Injury

    PubMed Central

    Anderson, Kim D.; Sharp, Kelli G.; Hofstadter, Maura; Irvine, Karen-Amanda; Murray, Marion; Steward, Oswald

    2009-01-01

    We describe here a novel Forelimb Locomotor Assessment Scale (FLAS) that assesses forelimb use during locomotion in rats injured at the cervical level. A quantitative scale was developed that measures movements of shoulder, elbow, and wrist joints, forepaw position and digit placement, forelimb-hindlimb coordination, compensatory behaviors adopted while walking, and balance. Female Sprague-Dawley rats received graded cervical contusions ranging from 200–230 (“mild”, n=11) and 250–290 kilodynes (“moderate”, n=13) between C5–8. Rats were videotaped post-injury as they walked along an alley to determine deficits and recovery of forelimb function. Recovery of shoulder and elbow joint movement occurred rapidly (within 1–7 days post-injury), whereas recovery of wrist joint movement was slower and more variable. Most rats in all groups displayed persistent deficits in forepaw and digit movement, but developed compensatory behaviors to allow functional forward locomotion within 1–2 weeks post-injury. Recovery of forelimb function as measured by the FLAS reached a plateau by 3 weeks post-injury in all groups. Rats with mild contusions displayed greater locomotor recovery than rats with moderate contusions, but exhibited persistent deficits compared to sham controls. Reliability was tested by having seven raters (3 internal, 4 external) from different laboratories, independently and blindly score videos of all rats. The multivariate correlation between all raters, all animals, and all time-points ranged from r2=0.88–0.96 (p<0.0001), indicating a high inter-rater reliability. Thus, the FLAS is a simple, inexpensive, sensitive, and reliable measure of forelimb function during locomotion following cervical SCI. PMID:19733168

  14. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  15. Oxymatrine reduces neuroinflammation in rat brain

    PubMed Central

    Mao, Jiahui; Hu, Yae; Zhou, Ailing; Zheng, Bing; Liu, Yi; Du, Yueming; Li, Jia; Lu, Jinyang; Zhou, Pengcheng

    2012-01-01

    Cerebral neuroinflammation models were established by injecting 10 ?g lipopolysaccharide into the hippocampus of male Sprague-Dawley rats. The rats were treated with an intraperitoneal injection of 120, 90, or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection. Twenty-four hours after model induction, the hippocampus was analyzed by real-time quantitative PCR, and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay. The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1? and tumor necrosis factor-? were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine. Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine. Additionally, 120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-?B p65 in the nucleus and of phosphorylated I?B? in the cytoplasm of brain cells, as detected by western blot assay. Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-?B signaling pathway. PMID:25538757

  16. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (?-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  17. Does reorganization in the cuneate nucleus following neonatal forelimb amputation influence development of anomalous circuits within the somatosensory cortex?

    PubMed

    Lane, Richard D; Pluto, Charles P; Kenmuir, Cynthia L; Chiaia, Nicolas L; Mooney, Richard D

    2008-02-01

    Neonatal forelimb amputation in rats produces sprouting of sciatic nerve afferent fibers into the cuneate nucleus (CN) and results in 40% of individual CN neurons expressing both forelimb-stump and hindlimb receptive fields. The forelimb-stump region of primary somatosensory cortex (S-I) of these rats contains neurons in layer IV that express both stump and hindlimb receptive fields. However, the source of the aberrant input is the S-I hindlimb region conveyed to the S-I forelimb-stump region via intracortical projections. Although the reorganization in S-I reflects changes in cortical circuitry, it is possible that these in turn are dependent on the CN reorganization. The present study was designed to directly test whether the sprouting of sciatic afferents into the CN is required for expression of the hindlimb inputs in the S-I forelimb-stump field. To inhibit sprouting, neurotrophin-3 (NT-3) was applied to the cut nerves following amputation. At P60 or older, NT-3-treated rats showed minimal sciatic nerve fibers in the CN. Multiunit electrophysiological recordings in the CN of NT-3-treated, amputated rats revealed 6.3% of sites were both stump/hindlimb responsive, compared with 30.5% in saline-treated amputated animals. Evaluation of the S-I following GABA receptor blockade, revealed that the percentage of hindlimb responsive sites in the stump representation of the NT-3-treated rats (34.2%) was not significantly different from that in saline-treated rats (31.5%). These results indicate that brain stem reorganization in the form of sprouting of sciatic afferents into the CN is not necessary for development of anomalous hindlimb receptive fields within the S-I forelimb/stump region. PMID:18032566

  18. Restraint of Fgf8 signaling by retinoic acid signaling is required for proper heart and forelimb formation

    PubMed Central

    Sorrell, Mollie R. Johnson; Waxman, Joshua S.

    2011-01-01

    Cardiomelic or heart-hand syndromes include congenital defects affecting both the forelimb and heart, suggesting a hypothesis where similar signals may coordinate their development. In support of this hypothesis, we have recently defined a mechanism by which retinoic acid (RA) signaling acts on the forelimb progenitors to indirectly restrict cardiac cell number. However, we still do not have a complete understanding of the mechanisms downstream of RA signaling that allow for the coordinated development of these structures. Here, we test the hypothesis that appropriate Fgf signaling in the cardiac progenitor field downstream of RA signaling is required for the coordinated development of the heart and forelimb. Consistent with this hypothesis, we find that increasing Fgf signaling can autonomously increase cardiac cell number and non-autonomously inhibit forelimb formation over the same time period that embryos are sensitive to loss of RA signaling. Furthermore, we find that Fgf8a, which is expressed in the cardiac progenitors, is expanded into the posterior in RA signaling-deficient zebrafish embryos. Reducing Fgf8a function in RA signaling-deficient embryos is able to rescue both heart and forelimb development. Together, these results are the first to directly support the hypothesis that RA signaling is required shortly after gastrulation in the forelimb field to temper Fgf8a signaling in the cardiac field, thus coordinating the development of the heart and forelimb. PMID:21803036

  19. Evolution of forelimb movement patterns for prey manipulation in anurans

    Microsoft Academic Search

    Lucie A. Gray; James C. O'Reilly; Kiisa C. Nishikawa

    1997-01-01

    Unlike other amphibians, frogs often use their forelimbs to capture and transport prey. In the present study, high-speed videography was used to observe forelimb use during feed- ing in a diverse group of anurans in order to determine the evolution of forelimb movement pat- terns among anuran taxa. Data were gathered from 488 individuals representing 104 species, 55 genera, and

  20. Neuromuscular anatomy and evolution of the cetacean forelimb.

    PubMed

    Cooper, Lisa Noelle; Dawson, Susan D; Reidenberg, Joy S; Berta, Annalisa

    2007-09-01

    The forelimb of cetaceans (whales, dolphins, and porpoises) has been radically modified during the limb-to-flipper transition. Extant cetaceans have a soft tissue flipper encasing the manus and acting as a hydrofoil to generate lift. The neuromuscular anatomy that controls flipper movement, however, is poorly understood. This study documents flipper neuromuscular anatomy and tests the hypothesis that antebrachial muscle robustness is related to body size. Data were gathered during dissections of 22 flippers, representing 15 species (7 odontocetes, 15 mysticetes). Results were compared with published descriptions of both artiodactyls and secondarily aquatic vertebrates. Results indicate muscle robustness is best predicted by taxonomic distribution and is not a function of body size. All cetaceans have atrophied triceps muscles, an immobile cubital joint, and lack most connective tissue structures and manus muscles. Forelimbs retain only three muscle groups: triceps (only the scapular head is functional as the humeral heads are vestigal), and antebrachial extensors and flexors. Well-developed flexor and extensor muscles were found in mysticetes and basal odontocetes (i.e., physeterids, kogiids, and ziphiids), whereas later diverging odontocetes (i.e., monodontids, phocoenids, and delphinids) lack or reduce these muscles. Balaenopterid mysticetes (e.g., fin and minke whales) may actively change flipper curvature, while basal odontocetes (e.g., sperm and beaked whales) probably stiffen the flipper through isometric contraction. Later diverging odontocetes lack musculature supporting digital movements and are unable to manipulate flipper curvature. Cetacean forelimbs are unique in that they have lost agility and several soft tissue structures, but retain sensory innervations. PMID:17721984

  1. Interlimb coordination in 20-day-old rat fetuses.

    PubMed

    Bekoff, A; Lau, B

    1980-11-01

    Evidence for short sequences of interlimb coordination was found in 20-day-old rat fetuses. Frame-by-frame analysis of videotape records showed phase relationships indicating a pattern of alternation in sequences involving forelimb-forelimb and hindlimb-hindlimb coordination. Forelimb-hindlimb coordination was not observed. PMID:7462983

  2. Neurobiology of Disease Subthalamic Stimulation-Induced Forelimb Dyskinesias Are

    E-print Network

    Paris-Sud XI, Université de

    Neurobiology of Disease Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked The neurobiological mechanisms by which high-frequency stimulation of the subthalamic nucleus (STN­HFS) alleviates

  3. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats.

    PubMed

    Skoczy?ska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, ?ukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100?ppm?Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2?mL/kg?b.w.) or egg derived lecithin fraction: "super lecithin" (50?g/kg?b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  4. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczy?ska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, ?ukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100?ppm?Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2?mL/kg?b.w.) or egg derived lecithin fraction: “super lecithin” (50?g/kg?b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05).

  5. The Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale: An Assessment of Reliability and Validity

    PubMed Central

    Irvine, Karen-Amanda; Ferguson, Adam R.; Mitchell, Kathleen D.; Beattie, Stephanie B.; Lin, Amity; Stuck, Ellen D.; Huie, J. Russell; Nielson, Jessica L.; Talbott, Jason F.; Inoue, Tomoo; Beattie, Michael S.; Bresnahan, Jacqueline C.

    2014-01-01

    The IBB scale is a recently developed forelimb scale for the assessment of fine control of the forelimb and digits after cervical spinal cord injury [SCI; (1)]. The present paper describes the assessment of inter-rater reliability and face, concurrent and construct validity of this scale following SCI. It demonstrates that the IBB is a reliable and valid scale that is sensitive to severity of SCI and to recovery over time. In addition, the IBB correlates with other outcome measures and is highly predictive of biological measures of tissue pathology. Multivariate analysis using principal component analysis (PCA) demonstrates that the IBB is highly predictive of the syndromic outcome after SCI (2), and is among the best predictors of bio-behavioral function, based on strong construct validity. Altogether, the data suggest that the IBB, especially in concert with other measures, is a reliable and valid tool for assessing neurological deficits in fine motor control of the distal forelimb, and represents a powerful addition to multivariate outcome batteries aimed at documenting recovery of function after cervical SCI in rats. PMID:25071704

  6. Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability

    PubMed Central

    Modi, Hiren R.; Taha, Ameer Y.; Kim, Hyung-Wook; Chang, Lisa; Rapoport, Stanley I.; Cheon, Yewon

    2012-01-01

    Chronic administration of mood stabilizers to rats downregulates the brain arachidonic acid (AA) cascade. This downregulation may explain their efficacy against bipolar disorder (BD), in which brain AA cascade markers are elevated. The atypical antipsychotics, olanzapine (OLZ) and clozapine (CLZ), also act against BD. When given to rats, both reduce brain cyclooxygenase activity and prostaglandin E2 concentration; OLZ also reduces rat plasma unesterified and esterified AA concentrations, and AA incorporation and turnover in brain phospholipid. To test whether CLZ produces similar changes, we used our in vivo fatty acid method in rats given 10 mg/kg/day i.p. CLZ, or vehicle, for 30 days; or 1 day after CLZ washout. [1-14C]AA was infused intravenously for 5 min, arterial plasma was collected and microwaved brain was analyzed. CLZ increased incorporation coefficients ki? and rates Jin,i of plasma unesterified AA into brain phospholipids i, while decreasing plasma unesterified but not esterified AA. These effects disappeared after washout. Thus, CLZ and OLZ similarly downregulated kinetics and cyclooxygenase expression of the brain AA cascade, likely by reducing plasma unesterified AA availability. Atypical antipsychotics and mood stabilizers may be therapeutic in BD by downregulating, indirectly or directly respectively, the elevated brain AA cascade of that disease. PMID:23121637

  7. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    PubMed Central

    Lysne, Vegard; Bjřrndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygĺrd, Ottar; Berge, Rolf K.

    2015-01-01

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

  8. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats.

    PubMed

    Lysne, Vegard; Bjřrndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygĺrd, Ottar; Berge, Rolf K

    2015-01-01

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

  9. Enoxaparin reduces cerebral edemaafter photothrombotic injury in the rat.

    PubMed

    Pratt, J; Boudeau, P; Uzan, A; Imperato, A; Stutzmann, J

    1998-01-01

    This study investigates the effect of enoxaparin (Lovenox, Klexane), a low-molecular-weight heparin, on edema following a photothrombotic lesion using rose bengal dye in the rat. An area of cerebral ischemia was provoked in the right hemisphere of rats. Edema developed over 24 h after the lesion, as seen comparing water content of a core sample from the right hemisphere to that of a similar sample from the left hemisphere of each rat. Enoxaparin at 0. 5 mg/kg i.v. plus 2 mg/kg s.c. reduced edema 24 h after lesion induction by 32% (p < 0.01) when the treatment was started 2 h after photothrombotic insult, with maintenance doses of 2 mg/kg s.c. enoxaparin at 6 and 18 h. When the same initial treatment with enoxaparin was started 18 h after insult, there was still a significant reduction of 20% (p < 0.01) in cerebral edema. Administration of enoxaparin 18 h after insult reduced cerebral edema in a dose-dependent manner. There was no evidence of intracranial hemorrhages in any of the animal groups and when the hemoglobin content of the brain samples was assayed by the method of Drabkin, no increase in hemoglobin content was seen compared to sham-operated animals. PMID:10087432

  10. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    PubMed

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity. PMID:25904243

  11. 2-HYDROXYESTRADIOL ENHANCES BINGE ONSET IN FEMALE RATS AND REDUCES PREFRONTAL CORTICAL DOPAMINE IN MALE RATS

    PubMed Central

    R.K., Babbs; E.L., Unger; R.L.W., Corwin

    2013-01-01

    Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for four weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps < 0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps < 0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p < 0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established. PMID:23116652

  12. Noribogaine reduces nicotine self-administration in rats.

    PubMed

    Chang, Qing; Hanania, Taleen; Mash, Deborah C; Maillet, Emeline L

    2015-06-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats' levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  13. Noribogaine reduces nicotine self-administration in rats

    PubMed Central

    Chang, Qing; Hanania, Taleen; Mash, Deborah C

    2015-01-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  14. Curcumin reduces injury progression in a rat comb burn model.

    PubMed

    Singer, Adam J; Taira, Breena R; Lin, Fubao; Lim, Taeho; Anderson, Ryon; McClain, Steve A; Clark, Richard A F

    2011-01-01

    The oriental spice curcumin has anti-inflammatory and antioxidant effects. When given orally before injury, curcumin reduces burn progression in a rat comb burn model. The authors hypothesized that intravenous administration of curcumin after injury would reduce burn progression and that its effects are mediated through iron chelation. Two comb burns were created on the dorsum of Sprague-Dawley rats (weight, 300 g) using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds resulting in four rectangular 10 × 20 mm full-thickness burns separated by three 5 × 20 mm unburned interspaces (zone of ischemia). Animals were randomized to receive one of four doses of crude curcumin or one of six doses of purified curcumin intravenously 1 and 24 hours after injury. Another set of animals were randomized to deferoxamine or control vehicle. Wounds were observed at 7 days after injury for visual evidence of necrosis in the unburned interspaces. Full-thickness biopsies from the interspaces were evaluated with Hematoxylin and Eosin staining 7 days after injury for evidence of necrosis. The percentage of unburned interspaces undergoing necrosis at 1 week by purified curcumin doses was 0 ?g/kg, 74%; 0.3 ?g/kg, 58%; 1 ?g/kg, 53%; 3 ?g/kg, 37%; 10 ?g/kg, 63%; 30 ?g/kg, 53%; and 100 ?g/kg, 26%. The differences among the groups were significant (P = .03). When compared with controls, the 1 and 3 ?g/kg curcumin treatment groups had significantly less progression of interspaces to necrosis (P = .04 and .002) as did the 30 and 100 ?g/kg treatment groups (P = .03 and <.001). Deferoxamine did not reduce burn progression. When administered intravenously 1 and 24 hours after injury, both crude and purified curcumin reduce the percentage of unburned interspaces that undergo necrosis in a rat hot comb burn model. The effects of purified curcumin appear to be bimodal, suggesting more than one mechanism of action. The effects of curcumin do not appear to be mediated by iron chelation. PMID:21088615

  15. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

    Azim, Eiman; Fink, Andrew J.P.; Jessell, Thomas M.

    2015-01-01

    Skilled motor behavior emerges from interactions between efferent neural pathways that induce muscle contraction and feedback systems that report and refine movement. Two broad classes of feedback projections modify motor output, one from the periphery and a second that originates within the central nervous system. The mechanisms through which these pathways influence movement remain poorly understood, however. Here we discuss recent studies that delineate spinal circuitry that binds external and internal feedback pathways to forelimb motor behavior. A spinal presynaptic inhibitory circuit regulates the strength of external feedback, promoting limb stability during goal-directed reaching. A distinct excitatory propriospinal circuit conveys copies of motor commands to the cerebellum, establishing an internal feedback loop that rapidly modulates forelimb motor output. The behavioral consequences of manipulating these two circuits reveal distinct controls on motor performance, and provide an initial insight into feedback strategies that underlie skilled forelimb movement. PMID:25699987

  16. Ventricular arrhythmia incidence in the rat is reduced by naloxone.

    PubMed

    Pugsley, M K; Hayes, E S; Wang, W Q; Walker, M J A

    2015-07-01

    This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32?mol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32?mol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels. PMID:25920674

  17. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke

    E-print Network

    O'Toole, Alice J.

    Vagus nerve stimulation during rehabilitative training improves forelimb strength following: Vagus nerve stimulation Plasticity Neurorehabilitation Motor cortex Stroke Ischemia Upper limb have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb

  18. Reduced T cell response in carcinogen-sensitive Donryu rats compared with carcinogen-resistant DRH rats.

    PubMed

    Mise-Omata, S; Sugiura, T; Higashi, K; Yamashita, U

    1999-12-01

    Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3'-methyl-4-dimethyl-amino-azobenzene (3'-MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) complex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts to exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats. Flow cytometric analysis revealed that the expression of CD4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These results indicate that Donryu rats, which have been used in many years for cancer research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibility to transplanted tumor cells of Donryu rats. PMID:10665643

  19. Fenofibrate reduces adiposity in pregnant and virgin rats but through different mechanisms.

    PubMed

    Gonzalez, Maréa del Carmen; Vidal, Hubert; Herrera, Emilio; Bocos, Carlos

    2009-10-31

    Fenofibrate has been proven to reduce adiposity. Since gestation produces an increase in white adipose tissue (WAT) mass, we comparatively studied this drug-effect in virgin and pregnant rats. Fenofibrate reduced lumbar WAT weight in both pregnant and virgin rats. Fenofibrate treatment did not modify plasma free fatty acid (FFA) concentration in virgin rats, it greatly increased it in pregnant animals. Remarkable differences between the two groups were obtained for two proteins related to fatty acid oxidation and esterification and storing. Respectively, the mRNA levels of carnitine palmitoyltransferase I (CPT-I) were increased by the fenofibrate only in the virgin rats and a similar finding was observed for the expression of phosphoenolpyruvate carboxykinase (PEPCK). These findings indicate that fenofibrate reduces adiposity in pregnant and virgin rats through different mechanisms: a) in virgin rats, by promoting fatty acid oxidation; and b) in pregnant rats, by enhancing fatty acid output. PMID:19874714

  20. Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse

    PubMed Central

    BARBE, Mary F.; JAIN, Nisha X.; MASSICOTTE, Vicky S.; POPOFF, Steven N.; BARR-GILLESPIE, Ann E.

    2015-01-01

    We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions. PMID:25739896

  1. Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse.

    PubMed

    Barbe, Mary F; Jain, Nisha X; Massicotte, Vicky S; Popoff, Steven N; Barr-Gillespie, Ann E

    2015-06-10

    We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions. PMID:25739896

  2. Forelimb-hindlimb developmental timing changes across tetrapod phylogeny

    PubMed Central

    Bininda-Emonds, Olaf RP; Jeffery, Jonathan E; Sánchez-Villagra, Marcelo R; Hanken, James; Colbert, Matthew; Pieau, Claude; Selwood, Lynne; ten Cate, Carel; Raynaud, Albert; Osabutey, Casmile K; Richardson, Michael K

    2007-01-01

    Background Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony) to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole-mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb. Results An overall pattern of change across tetrapods can be discerned and appears to be relatively clade-specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/pectoral fin develops earlier than the hindlimb/pelvic fin. This pattern is either retained or re-evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons) and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs. Conclusion Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this trait means that changes in chondrogenetic patterns may serve as useful phylogenetic characters at higher taxonomic levels in tetrapods. Our results highlight the more important role generally played by allometric heterochrony in this instance to shape adult morphology. PMID:17908305

  3. Exercise training reduces insulin resistance in postmyocardial infarction rats

    PubMed Central

    Wang, Youhua; Tian, Zhenjun; Zang, Weijin; Jiang, Hongke; Li, Youyou; Wang, Shengpeng; Chen, Shengfeng

    2015-01-01

    Myocardial infarction (MI) induces cardiac dysfunction and insulin resistance (IR). This study examines the effects of MI-related IR on vasorelaxation and its underlying mechanisms, with a specific focus on the role of exercise in reversing the impaired vasorelaxation. Adult male Sprague–Dawley rats were divided into three groups: Sham, MI, and MI+Exercise. MI+Exercise rats were subjected to 8 weeks of treadmill training. Cardiac contraction, myocardial and arterial structure, vasorelaxation, levels of inflammatory cytokines, expression of eNOS and TNF-?, and activation of PI3K/Akt/eNOS and p38 mitogen-activated protein kinase (p38 MAPK) were determined in aortas. MI significantly impaired endothelial structure and vasodilation (P < 0.05–0.01), as indicated by decreased arterial vasorelaxation to ACh and insulin. MI also attenuated the myocardial contractile response, decreased aortic PI3K/Akt/eNOS expression and phosphorylation by insulin, and increased IL-1?, IL-6, and TNF-? expression and p38 MAPK activity (P < 0.05–0.01). Exercise improved insulin sensitivity in aortas, facilitated myocardial contractile response and arterial vasorelaxation to ACh and insulin, and increased arterial PI3K/Akt/eNOS activity. Moreover, exercise markedly reversed increased p38 MAPK activity and normalized inflammatory cytokines in post-MI arteries. Inhibition of PI3K with LY-294002, and eNOS with L-NAME significantly blocked arterial vasorelaxation and PI3K/Akt/eNOS phosphorylation in response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin plays an important role in MI-related IR. The reversal of IR by exercise is most likely associated with normalizing inflammatory cytokines, increasing the activation of PI3K/Akt/eNOS, and reducing the activation of p38 MAPK. PMID:25907785

  4. Phosphate restriction significantly reduces mortality in uremic rats with established vascular calcification.

    PubMed

    Finch, Jane L; Lee, Duk H; Liapis, Helen; Ritter, Cindy; Zhang, Sarah; Suarez, Edu; Ferder, Leon; Slatopolsky, Eduardo

    2013-12-01

    The role of hyperphosphatemia in the pathogenesis of secondary hyperparathyroidism, cardiovascular disease, and progression of renal failure is widely known. Here we studied effects of dietary phosphate restriction on mortality and vascular calcification in uremic rats. Control and uremic rats were fed a high-phosphate diet and at 3 months a portion of rats of each group were killed. Serum phosphate and the calcium phosphate product increased in uremic rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were continued on diets containing high phosphate without and with sevelamer, or low phosphate, and after 3 more months they were killed. Serum phosphate was highest in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation than those of uremic rats on high phosphate. Importantly, kidneys from rats on low phosphate showed improvement over kidneys from high-phosphate rats at 3 months. Left ventricles from rats on low phosphate had less perivascular fibrosis and smaller cardiomyocyte size compared to rats on high phosphate. Thus, intensive phosphate restriction significantly reduces mortality in uremic rats with severe vascular calcification. PMID:24107846

  5. Macelignan attenuates LPS-induced inflammation and reduces LPS-induced spatial learning impairments in rats.

    PubMed

    Cui, Chun-Ai; Jin, Da-Qing; Hwang, Yoo Kyeong; Lee, Im-Soon; Hwang, Jae Kwan; Ha, Ilho; Han, Jung-Soo

    2008-12-19

    Previous studies have shown that macelignan has anti-inflammatory and neuroprotective effects. Subsequently, in the current study, we demonstrate that oral administrations of macelignan reduce the hippocampal microglial activation induced by chronic infusions of lipopolysaccharide (LPS) into the fourth ventricle of Fisher-344 rat brains. A Morris water maze was used to evaluate the status of the hippocampal-dependent spatial learning in control rats with an artificial cerebrospinal fluid infusion, rats with chronic LPS infusions, and rats with chronic LPS infusions and oral administrations of macelignan. The rats with chronic LPS infusions showed spatial memory impairments relative to the control rats in the performance of the memory task. Daily administration of macelignan reduced the spatial memory impairments induced by the chronic LPS infusions. The results indicate that macelignan may possess therapeutic potential for the prevention of Alzheimer's disease. PMID:18940231

  6. Reconstructing the locomotor repertoire of Protopithecus brasiliensis. II. Forelimb morphology.

    PubMed

    Halenar, Lauren B

    2011-12-01

    The majority of previous publications have suggested that the large-bodied subfossil Protopithecus brasiliensis was a suspensory ateline with a locomotor repertoire similar to that of extant Ateles and Brachyteles. This is unexpected, as the cranial morphology of Protopithecus is very similar to Alouatta, a genus usually classified as a deliberate quadrupedal climber. Complicating matters further, as Protopithecus is twice as large as Ateles and Brachyteles, its ability to be as suspensory as those two genera is suspect and a terrestrial component of the locomotor repertoire has also been hypothesized. The forelimbs of Protopithecus, while relatively elongated as would be expected in a suspensory animal, are also quite robust and show several adaptations for climbing. To test these hypotheses about the fossil locomotor repertoire, three-dimensional geometric morphometric techniques were used to quantify the shapes of the fossil distal humerus and proximal ulna and then compare them to a broad sample of extant primates with varying body sizes and locomotor patterns. Results indicate that Protopithecus is similar to Ateles and Brachyteles in terms of its forelimb joint surface morphology; however, the overall locomotor repertoire of the fossil is reconstructed as more flexible to include forelimb suspension, climbing, and potentially some terrestrial ground use. The combination of suspensory locomotion and quadrupedal climbing supported here indicates the beginnings of the evolutionary transition from a more acrobatic style of locomotion in the last common ancestor of alouattins and atelins to the current pattern of howler locomotion. PMID:22042627

  7. Poly(ADP-Ribose) Synthase Inhibition Reduces Ischemic Injury and Inflammation in Neonatal Rat Brain

    E-print Network

    Cossart, Rosa

    with reperfusion and may be of interest for the treatment of neonatal stroke. Key Words: Cell death--NeonatalPoly(ADP-Ribose) Synthase Inhibition Reduces Ischemic Injury and Inflammation in Neonatal Rat Brain responses, and (c) functional outcomes in a neonatal rat model of focal ischemia. We demonstrate

  8. Endotoxin-induced mortality in rats is reduced by nitrones

    SciTech Connect

    Hamburger, S.A.; McCay, P.B. (Oklahoma Medical Researh Foundation, Oklahoma City (USA))

    1989-12-01

    The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF, and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.

  9. Effects of canrenone on blood pressure in rats with reduced renal mass.

    PubMed

    Pamnani, M B; Whitehorn, W V; Clough, D L; Haddy, F J

    1990-03-01

    Canrenone, a metabolic product of spironolactone, which competes with ouabain for binding to Na-K-ATPase at the digitalis receptor site and by itself inhibits Na-K-ATPase, was administered intramuscularly to reduced renal mass-saline drinking hypertensive and reduced renal mass-distilled water drinking normotensive rats for 8 days. Reduced renal mass-saline hypertension in the rat, is a low renin, volume expanded form of hypertension. Rats with this type of hypertension have been shown to have depressed arterial Na-K pump activity and increased Na-K pump inhibitory activity in their plasma. Canrenone treatment caused a progressive decrease in blood pressure in the hypertensive rats and this was associated with normalization of Na-K pump activity in arteries. Water and salt intake and excretion did not change. On the other hand, canrenone progressively increased blood pressure in the normotensive rats and this was associated with positive inotropy in isolated papillary muscles. These findings suggest that the depressed pump activity and the pump inhibitor play a role in reduced renal mass-saline hypertension in the rat and that the rise in blood pressure in the normotensive rats probably reflects canrenone's ability, by itself, to inhibit Na-K-ATPase. PMID:2157466

  10. Immediate Postsession Feeding Reduces Operant Responding in Rats

    ERIC Educational Resources Information Center

    Smethells, John R.; Fox, Andrew T.; Andrews, Jennifer J.; Reilly, Mark P.

    2012-01-01

    Three experiments investigated the effects of immediate and delayed postsession feeding on progressive-ratio and variable-interval schedule performance in rats. During Experiments 1 and 2, immediate postsession feeding decreased the breakpoint, or largest completed ratio, under progressive-ratio schedules. Experiment 3 was conducted to extend the…

  11. Butter-enriched diets reduce arterial prostacyclin production in rats.

    PubMed

    O'Dea, K; Steel, M; Naughton, J; Sinclair, A; Hopkins, G; Angus, J; He, G W; Niall, M; Martin, T J

    1988-03-01

    Rats were fed diets containing 10%, 30% or 50% energy as fat derived predominantly from butter or lard. The protein content of the diets was maintained at 20%. After three weeks on the diets, the rats were killed and the following parameters measured: prostacyclin production in vitro from abdominal aorta and mesenteric artery; platelet aggregation to ADP and thrombin; fatty acid composition of the phospholipids in plasma, thoracic aorta and liver; smooth muscle reactivity and release of endothelial derived relaxing factor (EDRF) from aortic endothelium stimulated by acetylcholine. There was no significant effect of increasing fat content of the diets (neither lard nor butter) on platelet aggregation. In contrast, prostacyclin production in both the mesenteric artery and the abdominal aorta fell in a concentration-dependent manner in the butter-supplemented rats. However, no effect on prostacyclin production was detected in arteries from the lard-supplemented animals. The effects of the diets on prostacyclin (PGI2) production correlated very well with the changes in plasma, aortic and liver phospholipid arachidonic acid (AA) and eicosapentaenoic acid (EPA) contents. AA decreased in a concentration-dependent manner in the rats fed the butter-enriched diets but did not change in those fed the lard-enriched diets, whereas EPA rose in a concentration-dependent manner in the butter-fed rats and was unchanged in the lard-fed animals. The clear-cut effects of the butter-enriched diets on aortic phospholipid fatty acid composition and aortic PGI2 production were accompanied by a significant reduction in smooth muscle relaxation to EDRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3287083

  12. Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity.

    PubMed

    Ji, H; Friedman, M I

    2008-08-01

    Rats vary in their propensity to become obese when eating a high-fat diet, but the factors that make some rats susceptible and others resistant to diet-induced obesity are unclear. Recent studies show that rats predisposed to diet-induced obesity have a preexisting deficit in fat oxidation and suggest that this impairment is due in part to reduced fatty acid oxidation in liver. To determine directly whether rats susceptible to diet-induced obesity are less able to oxidize fatty acids in liver, we measured palmitate oxidation in hepatocytes isolated from outbred Sprague-Dawley rats that were identified while still eating a low-fat diet as obesity-prone or obesity-resistant by using a new screening procedure based on the change in plasma triglyceride concentration produced by an intragastric load of a fat and carbohydrate mixture. The results showed that hepatocytes from rats thus identified as obesity-prone oxidized 44% less palmitate in vitro than did those from obesity-resistant rats. This difference in hepatocyte fatty acid oxidation is consistent with and may explain at least in part the reduced capacity of obesity-prone rats to oxidize fat. PMID:18504445

  13. Subdiaphragmatic vagotomy reduces intake of sweet-tasting solutions in rats?

    PubMed Central

    Jiang, Enshe; Yu, Dongming; Feng, Zhifen

    2013-01-01

    Studies have shown that there are strong interactions between gustatory and visceral sensations in the central nervous system when rats ingest sweet foods or solutions. To investigate the role of the subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats deprived of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water. PMID:25206451

  14. Reduced thioredoxin increases proinflammatory cytokines and neutrophil influx in rat airways: Modulation by airway mucus

    Microsoft Academic Search

    Raymond C. Rancourt; Rees L. Lee; Heidi O’Neill; Frank J. Accurso; Carl W. White

    2007-01-01

    Thioredoxin (Trx) decreases viscosity of cystic fibrosis (CF) sputum. In this study reduced Trx increased the solubility and decreased the size of MUC5B glycoprotein while reducing disulfide bonds in sputum. Because Trx used as a mucolytic would enter airways, this study determined the effects of intratracheal instillation of reduced recombinant human thioredoxin (rhTrx) in naďve rat airways. Reduced rhTrx increased

  15. A Three-Dimensional Analysis of Morphological Evolution and Locomotor Performance of the Carnivoran Forelimb

    PubMed Central

    Martín-Serra, Alberto; Figueirido, Borja; Palmqvist, Paul

    2014-01-01

    In this study, three-dimensional landmark-based methods of geometric morphometrics are used for estimating the influence of phylogeny, allometry and locomotor performance on forelimb shape in living and extinct carnivorans (Mammalia, Carnivora). The main objective is to investigate morphological convergences towards similar locomotor strategies in the shape of the major forelimb bones. Results indicate that both size and phylogeny have strong effects on the anatomy of all forelimb bones. In contrast, bone shape does not correlate in the living taxa with maximum running speed or daily movement distance, two proxies closely related to locomotor performance. A phylomorphospace approach showed that shape variation in forelimb bones mainly relates to changes in bone robustness. This indicates the presence of biomechanical constraints resulting from opposite demands for energetic efficiency in locomotion –which would require a slender forelimb– and resistance to stress –which would be satisfied by a robust forelimb–. Thus, we interpret that the need of maintaining a trade-off between both functional demands would limit shape variability in forelimb bones. Given that different situations can lead to one or another morphological solution, depending on the specific ecology of taxa, the evolution of forelimb morphology represents a remarkable “one-to-many mapping” case between anatomy and ecology. PMID:24454891

  16. Forelimbs of "Tyrannosaurus Rex": A Pathetic Vestigial Organ or an Integral Part of a Fearsome Predator?

    ERIC Educational Resources Information Center

    Lee, Scott A.; Thomas, Joshua D.

    2014-01-01

    In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of "Tyrannosaurus rex." A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of "T. rex" were too short to reach its mouth, what…

  17. Grape seed extract suppresses lipid peroxidation and reduces hypoxic ischemic brain injury in neonatal rats

    Microsoft Academic Search

    Yangzheng Feng; Yi-Ming Liu; Jonathan D. Fratkins; Michael H. LeBlanc

    2005-01-01

    Oxygen radicals play a crucial role in brain injury. Grape seed extract is a potent anti-oxidant. Does grape seed extract reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid arteries permanently ligated followed by 2.5h of hypoxia (8% oxygen). Grape seed extract, 50mg\\/kg, or vehicle was administered by i.p. 5min prior to hypoxia and 4h

  18. Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease

    Microsoft Academic Search

    Malcolm R. Ogborn; Evan Nitschmann; Neda Bankovic-Calic; Hope A. Weiler; Shirley Fitzpatrick-Wong; Harold M. Aukema

    2003-01-01

    Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease.BackgroundConjugated linoleic acid (CLA) describes positional isomers of linoleic acid (LA). Experimental health benefits of CLA include amelioration of malignancy and inflammatory disease and reduction of adiposity. The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable

  19. Telmisartan improves vascular function and reduces platelet activation in rats with streptozotocin-induced diabetes mellitus

    Microsoft Academic Search

    Andreas Schäfer; Ulrike Flierl; Christian Vogt; Stefanie Menninger; Piet Tas; Georg Ertl; Johann Bauersachs

    2007-01-01

    Diabetes is associated with vascular dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. We investigated whether the angiotensin II antagonist telmisartan improves vascular dysfunction and reduces platelet activation in diabetic rats. Therefore, male Wistar rats were injected with streptozotocin (50mgkg?1 i.v.) to induce insulin-deficient diabetes. Treatment with telmisartan (10mgkg?1day?1) or vehicle was initiated 2 weeks

  20. Sensorimotor cortical representation in the rat and the role of the cortex in the production of sensory myoclonic jerks.

    PubMed Central

    Angel, A; Lemon, R N

    1975-01-01

    1. After administration of 1,2-dihydroxybenzene (catechol) to anaesthetized rats, rabbits and cats, a reflex jerk consisting of three distinct components was evoked in the limb muscles by peripheral stimulation. The second component of the jerk in the forelimb muscles of all three animals was specifically abolished by lesions confined to the contralateral forelimb sensorimotor cortex. 2. These lesions had no effect on the second response in either the hind limbs or in the forelimb ipsilateral to the lesion. The first and third responses were also unaffected. 3. Lesions in the cat hind-limb cortex abolished the contralateral hind-limb second response, but not the ipsilateral hind-limb or forelimb response. 4. In the rat and rabbit, unilateral hind-limb sensorimotor lesions were ineffective in completely abolishing the second response in the contralateral hind-leg muscles, and in addition, reduced the probability of occurrence of the response in the ipsilateral hind leg. Bilateral lesions abolished the response. 5. Re-investigation of the sensory and motor representation of the hind limb in the rat cortex revealed that this is bilateral in nature. Short-latency cortical responses (ca. 7-0 msec) could be evoked in one cortex by stimulation of either hind paw. The geometric centre of the cortical area from which these responses could be recorded was identical for each hind paw. 6. After catechol injection, stimulation of the cortical surface with single anodal shocks of threshold strength produced responses at similar latency (ca. 8-0 msec) in both hind limbs. 7. The behaviour of the second response after cortical lesions corresponds closely with the pattern of the somatosensorimotor cortical representation. The latency of the response is such as to allow its production by a long-loop cortical reflex, and this possibility is discussed. PMID:1151793

  1. Immediate Postsession Feeding Reduces Operant Responding in Rats

    PubMed Central

    Smethells, John R; Fox, Andrew T; Andrews, Jennifer J; Reilly, Mark P

    2012-01-01

    Three experiments investigated the effects of immediate and delayed postsession feeding on progressive-ratio and variable-interval schedule performance in rats. During Experiments 1 and 2, immediate postsession feeding decreased the breakpoint, or largest completed ratio, under progressive-ratio schedules. Experiment 3 was conducted to extend the results of the first two experiments to responding maintained by variable-interval schedules with different session lengths (15 and 60 min). Response rates decreased in all 4 subjects when postsession feeding immediately followed a 15-min session and in 3 of 4 subjects when postsession feeding immediately followed a 60-min session. The implications of this research are twofold: (1) The functional context in which within-session reinforcers are embedded extends outside the experimental chamber, and (2) supplemental postsession feedings should be sufficiently delayed from the end of a session to avoid weakening operant behavior in the experimental sessions. PMID:22389526

  2. The number of lactotrophs is reduced in the anterior pituitary of streptozotocin-induced diabetic rats

    Microsoft Academic Search

    A. I. Arroba; L. M. Frago; C. Pańeda; J. Argente; J. A. Chowen

    2003-01-01

      \\u000a \\u000a Aims\\/hypothesis. Prolactin secretion is often reduced in insulin dependent diabetes mellitus, but little is known about the mechanism involved.\\u000a Since changes in the hormonal environment modulate cell proliferation, death and cellular makeup of the anterior pituitary,\\u000a we have analysed whether the number of lactotrophs is reduced in diabetic rats.\\u000a \\u000a \\u000a \\u000a \\u000a Methods. Streptozotocin induced diabetic rats were maintained hyperglycaemic for 2

  3. High-fat feeding reduced muscle uncoupling protein 3 expression in rats.

    PubMed

    Corbalán, M S; Margareto, J; Martínez, J A; Marti, A

    1999-06-01

    Uncoupling Protein 3 (UCP3), largely expressed in skeletal muscle, is modulated by cold, thyroid hormones, leptin, fasting-refeeding and exercise training among other factors in a tissue-specific manner. In brown adipose tissue, there is an increase in UCP3 levels after high-fat feeding and beta3-adrenergic agonist treatment. Controversial effects of these agents have been reported in skeletal muscle. The aim of this experimental trial was to evaluate the effect of high-fat feeding and beta3-adrenergic agent treatment on skeletal muscle UCP3 expression levels. Lean rats were fed a cafeteria diet for 30 days and found to have significantly higher fat stores and body weight than control rats at the end of the experimental period. When cafeteria-diet rats were daily i.p. injected with Tertatolol for 30 days; a decrease in total fat mass and body weight was found. Such an effect was not observed in fa/fa rats. Interestingly, gastrocnemius muscle UCP3 mRNA levels were significantly reduced in cafeteria-diet rats when compared to lean animals. Likewise, mitochondrial O2 consumption in gastrocnemius muscle was also significantly decreased (-31%) in cafeteria-diet rats as compared to the control group. It is suggested that the down-regulation of UCP3 gene expression together with the lower O2 consumption observed in high fat fed rats may be linked to lower fatty oxidation, which would promote triglyceride accumulation. PMID:10517262

  4. Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats

    PubMed Central

    Shi, Hongjuan; Yang, Xinxin; Zhao, Hui; Zhang, Shenyang; Zu, Jie; Zhang, Wei; Shen, Xia; Cui, Guiyun; Hua, Fang; Yan, Chuanzhu

    2015-01-01

    Background Levodopa (l-dopa) remains the best drug in the treatment of Parkinson’s disease (PD). Unfortunately, long-term l-dopa caused motor complications, one of which is l-dopa-induced dyskinesia (LID). The precise mechanisms of LID are not fully understood. We have previously reported that ranitidine could reduce LID by inhibiting the activity of protein kinase A pathway in a rat model of PD. It is demonstrated that neurotransmitters such as ?-aminobutyric-acid (GABA) and glutamate (Glu) are also involved in the expression of LID. But whether ranitidine could reduce LID by remodeling the neurochemical changes is unknown. Methods In the present study, we produced PD rats by injection of 6-hydroxydopamine. Then PD rats were treated with vehicle, l-dopa (6 mg/kg, plus benserazide 12 mg/kg, intraperitoneal [ip]) or l-dopa (6 mg/kg, plus benserazide 12 mg/kg, ip) plus ranitidine (10 mg/kg, oral). Abnormal voluntary movements were adopted to measure the antidyskinetic effect of ranitidine in PD rats. Rotarod tests were used to observe whether ranitidine treatment affects the antiparkinsonian effect of l-dopa. In vivo microdialysis was used to measure nigral GABA and striatal Glu in PD rats. Results We found that ranitidine pretreatment reduced abnormal voluntary movements in l-dopa-primed PD rats without affecting the antiparkinsonian effect of l-dopa. In parallel with behavioral improvement, ranitidine pretreatment reduced protein kinase A activity and suppressed the surge of nigral GABA and striatal Glu. Conclusion These data indicated that ranitidine could reduce LID by modeling neurochemical changes induced by l-dopa, suggesting a novel mechanism of ranitidine in the treatment of LID. PMID:26064051

  5. Morphological integration in the forelimb of musteloid carnivorans.

    PubMed

    Fabre, Anne-Claire; Goswami, Anjali; Peigné, Stéphane; Cornette, Raphaël

    2014-07-01

    The forelimb forms a functional unit that allows a variety of behaviours and needs to be mobile, yet at the same time stable. Both mobility and stability are controlled, amongst others, at the level of the elbow joint. This joint is composed of the humero-ulnar articulation, mainly involved during parasagittal movements; and the radio-ulnar articulation, mainly allowing rotation. In contrast, the humero-radial articulation allows both movements of flexion-extension and rotation. Here, we study the morphological integration between each bone of the forelimb at the level of the entire arm, as well as at the elbow joint, in musteloid carnivorans. To do so, we quantitatively test shape co-variation using surface 3D geometric morphometric data. Our results show that morphological integration is stronger for bones that form functional units. Different results are obtained depending on the level of investigation: for the entire arm, results show a greater degree of shape co-variation between long bones of the lower arm than between the humerus and either bone of the lower arm. Thus, at this level the functional unit of the lower arm is comprised of the radius and ulna, permitting rotational movements of the lower arm. At the level of the elbow, results display a stronger shape co-variation between bones allowing flexion and stability (humerus and ulna) than between bones allowing mobility (ulna and radius and humerus and radius). Thus, the critical functional unit appears to be the articulation between the humerus and ulna providing the stability of the joint. PMID:24836555

  6. Forelimb myology of the pygmy hippopotamus (Choeropsis liberiensis).

    PubMed

    Fisher, Rebecca E; Scott, Kathleen M; Naples, Virginia L

    2007-06-01

    Based on morphological analyses, hippos have traditionally been classified as Suiformes, along with pigs and peccaries. However, molecular data indicate hippos and cetaceans are sister taxa (see review in Uhen, 2007, this issue). This study analyzes soft tissue characters of the pygmy hippo forelimb to elucidate the functional anatomy and evolutionary relationships of hippos within Artiodactyla. Two specimens from the National Zoological Park in Washington, D.C. were dissected, revealing several adaptations to an aquatic lifestyle. However, these adaptations differ functionally from most aquatic mammals as hippos walk along river or lake bottoms, rather than swim. Several findings highlight a robust mechanism for propelling the trunk forward through the water. For example, mm. pectoralis superficialis and profundus demonstrate broad sites of origin, while the long flexor tendons serve each of the digits, reflecting the fact that all toes are weight-bearing. Pygmy hippos also have eight mm. interossei and a well-developed m. lumbricalis IV. Retention of intrinsic adductors functions to prevent splaying of the toes, an advantageous arrangement in an animal walking on muddy substrates. Published descriptions indicate common hippos share all of these features. Hippo and ruminant forelimbs share several traits; however, hippos are unique among artiodactyls in retaining several primitive muscles (e.g., mm. palmaris longus and flexor digitorum brevis). These findings are consistent with the hypothesis that hippos diverged from other Artiodactyla early in the history of this group. Additional analyses of hindlimb and axial muscles may help determine whether this trajectory was closely allied to that of Cetacea. PMID:17516432

  7. Hyperbaric oxygen therapy fails to reduce hydrocephalus formation following subarachnoid hemorrhage in rats

    PubMed Central

    2014-01-01

    Background & purpose Approximately 40% of hemorrhagic stroke survivors develop hydrocephalus. Hyperbaric oxygen (HBO) has been shown to be anti-inflammation following experimental stroke; however, its effect upon post-hemorrhagic hydrocephalus formation is not known. The objective of this study is to investigate whether HBO therapy can effectively reduce hydrocephalus formation and improve neurobehavioral functions in a rat model of subarachnoid hemorrhage (SAH). Method Thirty-eight male Sprague–Dawley rats (300-320 g) rats survived for 21 days from SAH by endovascular perforation or sham surgery were used. At 24 hours after SAH, HBO (3 atmospheres absolute) or normobaric oxygen (NBO) administrated for 1 hour once daily for a total of 7 days. Wire hanging and rotarod testing were conducted at 14 days after SAH, and cognitive functions were evaluated via the Morris water maze, between day 17 to day 21 after surgery. At day 21, rats were sacrificed and cerebroventricular volumes were measured histologically. Results Hydrocephalus exacerbated neurological deficits after SAH, and HBO multiple treatment tendentially improved the neurobehavioral functions. Spatial learning and memory deficits were noticed after SAH, and rats with hydrocephalus showed worse learning and memory abilities and HBO treatment showed a minor improvement. In the SAH group (room air) 4 rats showed an increased ventricular volume at day 21 after SAH-induction (n?=?10). HBO or NBO therapy did not alter the occurrence of hydrocephalus after SAH, as 4 rats in each of these groups showed an increased ventricular volume (n?=?10 per group). Conclusion Multiple HBO therapy does not ameliorate hydrocephalus formation in a rat model of SAH; however, HBO tendentially improved the neurological functions and spatial learning and memory abilities in rats with hydrocephalus. PMID:25132956

  8. Use of phenylpropanolamine to reduce nicotine cessation induced weight gain in rats

    Microsoft Academic Search

    Suzan E. Winders; Thane Dykstra; Mace C. Coday; John C. Amos; Mary R. Wilson; David R. Wilkins

    1992-01-01

    The present study was conducted to determine if phenylpropanolamine (PPA) administered during the first week of nicotine termination could reduce or eliminate the body weight rebound which accompanies nicotine cessation. Sprague-Dawley rats were administered nicotine for 2 weeks after which they received either PPA or saline for 1 week. Control animals received saline during both drug periods. Body weight, food

  9. Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model

    Microsoft Academic Search

    Michael S. Caplan; Susan Kaup; Tanya Russell; Matthew Lickerman; Michael Amer; Yu Xiao; Richard Thomson

    1999-01-01

    Background & Aims: Neonatal necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants partly caused by intestinal bacterial proliferation. Because bifidobacteria are thought to reduce the risk for intestinal disturbances associated with pathogenic bacterial colonization, we hypothesized that exogenous bifidobacterial supplementation to newborn rats would result in intestinal colonization and a reduction in the incidence of neonatal NEC.

  10. Tyrphostin AG556 reduces myocardial infarct size and improves cardiac performance in the rat

    Microsoft Academic Search

    Jacob George; Simon Biner; Pnina Keren; Iris Barshack; Iris Goldberg; Jack Sherez; Alexander Levitzki; Gad Keren; Arie Roth

    2003-01-01

    TNF-? is a proinflammatory cytokine, abundantly expressed after myocardial infarction. It has been suggested that it exhibits myocardial suppressive and cytotoxic effects. AG-556 is a tyrosine kinase inhibitor synthesized based on its ability to reduce TNF-? production and cell toxicity, and to improve experimental models mediated by TNF-? (i.e., peritontitis and experimental autoimmune encephalomyelitis). Daily, for 7 days, rats were

  11. Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

    PubMed Central

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+dep) compared with Na+-independent (Na+indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (Vmax), without changes in apparent Km for Na+indep transport in SHR compared with WKY rats. Total and Na+dep component of transport were increased, but Na+indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na+-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR. PMID:24587332

  12. Insulin-resistance reduces botulinum neurotoxin-type A induced prostatic atrophy and apoptosis in rats.

    PubMed

    Vikram, Ajit; Jena, Gopabandhu; Ramarao, Poduri

    2011-01-10

    Botulinum neurotoxin-type A (BoNTA) is an emerging therapeutic option for the treatment of benign prostatic hyperplasia. Recent reports indicate increased incidence of benign prostatic hyperplasia in the insulin-resistant individuals. Insulin-resistance is associated with the compensatory rise in the plasma insulin, which is known to have growth-promoting effects. The present study investigated the effect of insulin-resistance on the effectiveness of BoNTA in inducing prostatic atrophy in rats. Sprague-Dawley rats (200-220g), maintained on normal-pellet or high-fat diet, were injected in the ventral prostate with 200?l of saline or the same volume containing 5U BoNTA at the end of 9weeks and were sacrificed 3weeks later. Ventral prostate was carefully isolated, weighed, fixed and stained to examine the cellular morphology, cell death and proliferation. High-fat diet produced insulin-resistance, hyperinsulinemia and prostatic enlargement in rats. BoNTA caused prostatic atrophy and apoptosis in both insulin-resistant and insulin-sensitive rats. However, the effect of BoNTA was more prominent in insulin-sensitive rats (apoptosis-2 fold, prostatic atrophy-3 fold) as compared to the insulin-resistant rats. Significant increase in the phosphorylation of ERK-1/2 and expression of the proliferating cell nuclear antigen was observed in the prostate of insulin-resistant rats. In the present investigation we report that diet-induced insulin-resistance activates mitogenic signaling of insulin, increases cellular proliferation and reduces BoNTA-induced prostatic atrophy and apoptosis in rats. Results of the present study indicate that the insulin-resistance can affect the therapeutic outcome of BoNTA. PMID:20940009

  13. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.

    PubMed Central

    Anderson, S; Meyer, T W; Rennke, H G; Brenner, B M

    1985-01-01

    Micropuncture and morphologic studies were performed in four groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 3 received no specific therapy. Groups 2 and 4 were treated with the angiotensin I converting enzyme inhibitor, enalapril, 50 mg/liter of which was put in their drinking water. All rats were fed standard chow. Groups 1 and 2 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained the mean glomerular transcapillary hydraulic pressure gradient at near-normal levels without significantly compromising SNGFR and the glomerular capillary plasma flow rate, as compared with untreated group 1 rats. Groups 3 and 4 were studied 8 wk after renal ablation. Untreated group 3 rats demonstrated persistent systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and segmental sclerosis. In group 4 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 8-wk period and significantly limited the development of proteinuria and glomerular lesions. These studies suggest that control of glomerular hypertension effectively limits glomerular injury in rats with renal ablation, and further support the view that glomerular hemodynamic changes mediate progressive renal injury when nephron number is reduced. Images PMID:2993362

  14. Melatonin reduces cardiac remodeling and improves survival in rats with isoproterenol-induced heart failure.

    PubMed

    Simko, Fedor; Bednarova, Kristina Repova; Krajcirovicova, Kristina; Hrenak, Jaroslav; Celec, Peter; Kamodyova, Natalia; Gajdosechova, Lucia; Zorad, Stefan; Adamcova, Michaela

    2014-09-01

    Melatonin was previously shown to reduce blood pressure and left ventricular (LV) remodeling in several models of experimental heart damage. This study investigated whether melatonin prevents LV remodeling and improves survival in isoproterenol-induced heart failure. In the first experiment, four groups of 3-month-old male Wistar rats (12 per group) were treated for 2 wk as follows: controls, rats treated with melatonin (10 mg/kg/day) (M), rats treated with isoproterenol (5 mg/kg/day intraperitoneally the second week) (Iso), and rats treated with melatonin (2 wk) and isoproterenol (the second week) in corresponding doses (IsoM). In the second experiment, 30 rats were treated with isoproterenol and 30 rats with isoproterenol plus melatonin for a period of 28 days and their mortality was investigated. Isoproterenol-induced heart failure with hypertrophy of the left and right ventricles (LV, RV), lowered systolic blood pressure (SBP) and elevated pulmonary congestion. Fibrotic rebuilding was accompanied by alterations of tubulin level in the LV and oxidative stress development. Melatonin failed to reduce the weight of the LV or RV; however, it curtailed the weight of the lungs and attenuated the decline in SBP. Moreover, melatonin decreased the level of oxidative stress and of insoluble and total collagen and partly prevented the beta-tubulin alteration in the LV. Most importantly, melatonin reduced mortality and prolonged the average survival time. In conclusion, melatonin exerts cardioprotective effects and improves outcome in a model of isoproterenol-induced heart damage. The antiremodeling effect of melatonin may be of potential benefit in patients with heart failure. PMID:24942291

  15. Cardiac ?-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses

    PubMed Central

    Haley, James M.; Thackeray, James T.; Thorn, Stephanie L.; DaSilva, Jean N.

    2015-01-01

    Objectives Reduced cardiac ?-adrenoceptor (?-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac ?-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac ?-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats. Methods Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of ?-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured. Results At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced ?-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal ?1-AR (98±9%), reduced ?2-AR (76±10%), and elevated ?3-AR (108±6). At 16 weeks, ?1-AR expression became reduced (69±16%), ?2-AR expression decreased further (68±14%), and ?3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function. Conclusions Cardiac ?-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and ?1- and ?2-AR expression are inversely correlated with the progression of type-2 diabetes. PMID:25996498

  16. INTRODUCTION The forelimb and hindlimb buds are derived from territories of

    E-print Network

    Tabin, Cliff

    in human TBX5 cause Holt-Oram Syndrome (HOS, OMIM 142900), a dominant disorder characterised predominantly of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt formation and continued outgr

  17. [Influence of the neck muscles deafferentation on the natural head-forelimb coordination in dogs].

    PubMed

    Pavlova, O G; Iuchkina, O V

    2005-01-01

    We studied the influence of the neck muscles deafferentation on the natural head-forelimb coordination. This coordination exists in intact dogs at the early stage of acquisition of the instrumental feeding reaction of tonic forelimb flexion aimed at holding a cup with meat during eating when the head is bent down to foodwell. In untrained dogs, the forelimb flexion is preceded by lifting the head bent down to the food; the following lowering of the head leads to extension of the flexed forelimb. For performing the instrumental reaction, the innate coordination has to be rearranged into the opposite one. It is achieved only by learning. It was shown that deafferentation of the neck muscles, which leads to a loss of the neck reflex, did not destroy the innate coordination and did not facilitate its rearrangement during the instrumental conditioning. PMID:16033243

  18. Forelimb regeneration from different levels of amputation in the newt, Notophthalmus viridescens : Length, rate, and stages

    Microsoft Academic Search

    Laurie E. Iten; Susan V. Bryant

    1973-01-01

    1.Some aspects of the influence of position on regeneration have been examined by comparing regeneration from two different levels along the newt forelimb.2.We have defined a series of stages of forelimb regeneration in the newt,Notophthalmus viridescens, in order to facilitate this study.3.Limbs amputated at either a proximal level (through the humerus) or a distal level (through the radius and ulna)

  19. Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats

    SciTech Connect

    Hadani, M.; Young, W.; Flamm, E.S.

    1988-09-01

    We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca/sup 2 +/, Na/sup +/, K/sup +/, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of (/sup 14/C)nicardipine into the brains of five rats; the highest concentrations of (/sup 14/C)nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca/sup 2 +/ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na/sup +/ and K/sup +/ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca/sup 2 +/ accumulation more than it reduces Na/sup +/ and water accumulation and K/sup +/ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca/sup 2 +/ entry into ischemic cells.

  20. [Role of different projection areas of the motor cortex in reorganization of the innate head-forelimb coordination in dogs].

    PubMed

    Pavlova, O G; Mats, V N

    2005-01-01

    Dogs were trained to perform the forelimb tonic flexion in order to lift a cup with meat from a bottom of the foodwell and hold it during eating with the head bent down to the cup. It is known that conditioning of the instrumental reaction is based on reorganization of the innate head-forelimb coordination into the opposite one. In untrained dogs, the forelimb flexion is accompanied by the anticipatory lifting of the head bent down to the foodwell. The following lowering of the head leads to an extension of the flexed forelimb. Tonic forelimb flexion is possible if the head is in the up position. Simultaneous holding of the flexed forelimb and lowered head providing food reinforcement is achieved only by learning. It was shown earlier that the lesion of the motor cortex contralateral to the "working" forelimb led to a prolonged disturbance of the elaborated coordination and reappearance of the innate coordination. In the present work we studied the influence of local lesions of the projection areas in the motor cortex, such as a "working" forelimb area, bilateral representation of the neck, and the medial part of the motor cortex, on the learned instrumental feeding reaction. It was found that only the lesion of the forelimb but not neck projection led to a disturbance of the learned head-forelimb movement coordination. PMID:16396488

  1. [Natural head-forelimb coordination in dogs after vestibular de-afferentation].

    PubMed

    Pavlova, O G; Iavorski?, A B

    2004-01-01

    We studied the influence of the vestibular lesion on the natural head--forelimb coordination. This coordination exists in intact dogs at the early stage of acquisition of the instrumental feeding reaction of tonic forelimb flexion in order to hold a cup with meat during eating when the head is bent down to foodwell. In untrained dogs, the forelimb flexion is preceded by lifting the head bent down to the food; the following lowering of the head leads to extension of the flexed forelimb. For performing the instrumental reaction, the innate coordination has to be rearranged into the opposite one. It is achieved only by learning. After the lesion of the primary motor cortex contralateral to the "working" forelimb in trained dogs, the innate coordination reappears, whereas the learned coordination breaks down steadily. It was shown that bilateral vestibular lesion do not disturb the innate coordination in intact dogs at the early stage of learning and in trained dogs after the motor cortex lesion. It was concluded that the studied natural head--forelimb coordination is not connected with the vestibular reflex. PMID:15658047

  2. Forelimbs of Tyrannosaurus Rex: A pathetic vestigial organ or an integral part of a fearsome predator?

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.; Thomas, Joshua D.

    2014-12-01

    In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of Tyrannosaurus rex. A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of T. rex were too short to reach its mouth, what function did the forelimbs serve? This issue crosses several scientific disciplines including paleontology, ecology, and physics, making it a great starting point for thinking "outside the box." Noted paleontologist Kenneth Carpenter has suggested that the forelimbs of T. rex were an integral part of its predatory behavior. Given the large teeth of T. rex, it is assumed that they killed with their teeth. Lipkin and Carpenter1 have suggested that the forelimbs were used to hold a struggling victim (which had not been dispatched with the first bite) while the final, lethal bite was applied. If that is the case, then the forelimbs must be capable of large angular accelerations ? in order to grab the animal attempting to escape. The concepts of the typical first-year physics course are sufficient to test this hypothesis by solving ? =? /I . Naturally, students love solving any problem related to Tyrannosaurus rex!

  3. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

    PubMed Central

    2014-01-01

    Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

  4. Diphenyl diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats.

    PubMed

    Dias, Glaecir Roseni Mundstock; de Almeida, Tielle Moraes; Sudati, Jéssie Haigert; Dobrachinski, Fernando; Pavin, Sandra; Soares, Félix Alexandre Antunes; Nogueira, Cristina Wayne; Barbosa, Nilda Berenice Vargas

    2014-01-30

    Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect. PMID:24239994

  5. Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats by inhibiting JAK/STAT signaling pathway

    PubMed Central

    Wang, Lijun; Li, Juan; Li, Dajun

    2015-01-01

    Purpose: This study was designed to investigate the effect of losartan on the myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) rats. Methods: In this study, a total of 48 male Wister rats (3 groups of 16 animals each) were examined, including the control group, DCM group and losartan-treated (DCM + L) group. Control group was fed with standard diet (14 KJ/g); DCM group and losartan-treated (DCM + L) group were both fed with high glucose and fat diet (20 KJ/g). Diabetes was induced by streptozotocin (STZ) intraperitoneal injuction (IP, 30 mg/kg body weight). Rats of DCM + L group were treated with losartan (30 mg/kg body weight) daily by oral gavage for 16 weeks. Biochemical, hemodynamic, histological and western blotting analyses were performed. Results: Compared with DCM rats, the quantity of p-JAK2 and p-STAT3 in myocardium of rats treated with losartan was lower, the expression of TGF-?1 was down-regulate, the content of collagen in myocardium decreased, LVSP and ± dp/dt increased, LVEDP decreased, the level of myocardial fibrosis reduced, and heart function improved evidently. Conclusion: Losartan has a protective effect on heart function against myocardial interstitial fibrosis of DCM by inhibiting JAK/STAT signaling pathway and lowering the expression of TGF-?1. PMID:25755735

  6. The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat.

    PubMed

    Castelló-Ruiz, María; Torregrosa, Germán; Burguete, María C; Miranda, Francisco J; Centeno, José M; López-Morales, Mikahela A; Gasull, Teresa; Alborch, Enrique

    2014-07-11

    While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17?-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) were achieved 4h after onset of ischemia, and maintained until the end of the procedure (24h). Neurofunctional score and volume of the damaged brain regions were the main end points. At 24h after ischemia-reperfusion, neurofunctional examination of the animals did not show significant differences among the three experimental groups. By contrast, both E2- and BZA-treated groups showed significantly lower total infarct volumes, BZA acting mainly in the cortical region and E2 acting mainly at the subcortical level. Our results demonstrate that: (1) E2 at physiological plasma levels in female rats is neuroprotective in male rats when given at the acute stage of the ischemic challenge and (2) BZA at clinically relevant plasma levels mimics the neuroprotective action of E2 and could be, therefore, a candidate in stroke treatment. PMID:24861515

  7. Visual targeting of forelimbs in ladder-walking locusts.

    PubMed

    Niven, Jeremy E; Buckingham, Christian J; Lumley, Sheila; Cuttle, Matthew F; Laughlin, Simon B

    2010-01-12

    Accurate limb placement helps animals and robots to walk on substrates that are uneven or contain gaps. Visual information is important in controlling limb placement in walking mammals but has received little attention in insects. We investigated whether desert locusts walking along a horizontal ladder use vision to control limb placement. High-speed video analysis showed that locusts targeted their front legs to specific rungs in the absence of any previous contact, suggesting that visual information alone is sufficient for targeting single steps. Comparison between the proportions of missed steps before and after monocular occlusion showed that monocular visual information was used to place the ipsilateral but not the contralateral front leg. Accurate placement also depended upon mechanosensory inputs from the antennae and proprioceptive feedback from the ipsilateral but not the contralateral forelimb. Locusts also compensated for the loss of inputs to one eye by altering their stepping pattern. Changing the rung position after initiation of a step showed that targeting of the front leg depends on visual information acquired before but not during a step. The trajectory was only modified after missing the rung. Our data show that locusts walking in environments where footholds are limited use visual and mechanosensory information to place their front legs. PMID:20036539

  8. Ancestry of motor innervation to pectoral fin and forelimb

    PubMed Central

    Ma, Leung-Hang; Gilland, Edwin; Bass, Andrew H.; Baker, Robert

    2010-01-01

    Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a hindbrain-spinal origin of motoneurons. Together, these findings support a hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the hindbrain much like their target appendage gained independence from the head. PMID:20975699

  9. Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats

    PubMed Central

    Shen, Ling; Xiong, Ye; Wang, David Q-H.; Howles, Philip; Basford, Joshua E.; Wang, Jiang; Xiong, Yu Qing; Hui, David Y.; Woods, Stephen C.; Liu, Min

    2013-01-01

    Ginsenoside Rb1 (Rb1), a natural compound extracted from ginseng, exerts anti-obesity activity and improves insulin sensitivity in high-fat diet (HFD)-induced obese rats. The objective of the current study was to evaluate the protective effect of Rb1 on fatty liver in HFD-induced obese rats and to elucidate underlying mechanisms. After chronic intraperitoneal administration, Rb1 (10 mg/kg) significantly ameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced liver weight, hepatic triglyceride content, and histological evaluation of liver sections by hematoxylin and eosin and Oil Red O staining. Using primary cultured rat hepatic cells, we found that the rate of fatty acid oxidation and the activity of carnitine palmitoyltransferase 1 (CPT1), a key enzyme in fatty acid ?-oxidation, were significantly elevated in Rb1-treated hepatocytes compared with those of vehicle-treated cells. HPLC analysis revealed that Rb1 increased the cellular AMP/ATP ratio, which is associated with elevated activation of hepatic AMP-activated protein kinase (AMPK) and phosphorylated acetyl-CoA carboxylase. Consistent with the activation of AMPK, Rb1 stimulated the expression of genes encoding fatty acid oxidative enzymes and proteins, and suppressed the expression of genes encoding enzymes or proteins that function in lipogenesis, assessed by quantitative PCR. We conclude that Rb1 has a potent ability to reduce hepatic fat accumulation and might be useful as a therapeutic agent for fatty liver disorder. PMID:23434611

  10. Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish

    PubMed Central

    Waxman, Joshua S.; Keegan, Brian R.; Roberts, Richard W.; Poss, Kenneth D.; Yelon, Deborah

    2009-01-01

    SUMMARY How adjacent organ fields communicate during development is not understood. Here, we identify a mechanism in which signaling within the forelimb field restricts the potential of the neighboring heart field. In zebrafish embryos deficient in retinoic acid (RA) signaling, the pectoral fins (forelimbs) are lost while both chambers of the heart are enlarged. We provide evidence that both of these phenotypes are due to RA signaling acting directly within the forelimb field. hoxb5b, an RA-responsive gene expressed within the forelimb field, is required to restrict the number of atrial cells arising from the adjacent heart field, although its function is dispensable for forelimb formation. Together, these data indicate non-autonomous influences downstream of RA signaling that act to limit individual chamber size. Therefore, our results offer new perspectives on the mechanisms regulating organ size and the possible causes of congenital syndromes affecting both the heart and forelimb. PMID:19081079

  11. Efficacy of activated diatomaceous clay in reducing the toxicity of zearalenone in rats and piglets.

    PubMed

    Denli, M; Blandon, J C; Guynot, M E; Salado, S; Pérez, J F

    2015-02-01

    Two experiments were conducted to evaluate the efficacy of an activated diatomaceous clay (ADC) in reducing the toxic effects of zearalenone (ZEA) in the diet of rats and piglets. In the rat experiment, 90 Sprague-Dawley female weanling rats with an initial BW of 45 ± 1.0 g were assigned to 1 of 6 dietary treatments for 28 d in a completely randomized design (CRD) with a 2 × 3 factorial arrangement (0 or 6 mg ZEA/kg feed and 0, 1, and 5 g ADC/kg feed). In the piglet experiment, 64 female piglets ([Large White × Landrace] × Pietrain with an initial BW of 14.9 ± 1.65 kg) were fed 1 of 8 experimental diets for 26 d in a CRD design with a 2 × 4 factorial arrangement (0 or 0.8 mg ZEA/kg feed and 0, 1, 2, and 5 g ADC/kg feed). The ADFI, ADG, and G:F were determined at the end of each experiment. At the conclusion of studies, serum samples were collected and rats and piglets were euthanized to determine visceral organ weights. The diet contaminated with ZEA did not alter the growth of rats and the relative weight of liver and kidneys. However, ZEA increased ( < 0.05) the relative weight of uterus, ovaries, and spleen and decreased ( < 0.05) the serum activities of alkaline phosphatase and alanine aminotransferase compared to the control group. Supplementation of ADC in the rat diets counteracted ( < 0.05) the observed toxic effects of ZEA on the uterus and ovaries weight. The diet contaminated with ZEA (0.8 mg/kg feed) increased ( < 0.05) the weight of the uterus and ovaries in piglets but did not modify the serum biochemical variables or the relative weight of other visceral organs. The addition of 5 g ADC/kg to the contaminated feed reduced the toxic effects of ZEA on uterus and ovary weights to that of the control group. Zearalenone (10.5 ?g/kg bile) and ?-zearalenol (5.6 ?g/kg bile) residues were detected in the bile of piglets fed the ZEA treatment. Supplementation of ADC to diets contaminated with ZEA reduced ( = 0.001) ZEA content in bile compared to the ZEA treatments. The results of these experiments indicate that a long-term consumption of ZEA-contaminated diets stimulated growth of the reproductive tract in rats and piglets and the presence of ZEA residue in bile in piglets. These effects may be counteracted by the addition of ADC to the diet. PMID:26020748

  12. Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats

    Microsoft Academic Search

    Daniele De Filippis; Livio Luongo; Mariateresa Cipriano; Enza Palazzo; Maria Pia Cinelli; Vito de Novellis; Sabatino Maione; Teresa Iuvone

    2011-01-01

    The aim of this study was to obtain evidences of a possible analgesic role for palmitoylethanolamide (PEA) in chronic granulomatous inflammation sustained by mast cell (MC) activation in rats at 96 hours. PEA (200-400-800 ?g\\/mL), locally administered at time 0, reduced in a concentration-dependent manner the expression and release of NGF in comparison with saline-treated controls. PEA prevented nerve formation

  13. Bryostatin improves survival and reduces ischemic brain injury in aged rats following acute ischemic stroke

    PubMed Central

    Tan, Zhenjun; Turner, Ryan C.; Leon, Rachel L.; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F.; Naser, Zachary J.; Alkon, Daniel L.; Rosen, Charles L.; Huber, Jason D.

    2014-01-01

    Background and Purpose Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer's disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator (tPA) reperfusion in aged rats. Methods Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20 month old female Sprague-Dawley rats using an autologous blood clot with tPA-mediated reperfusion. Bryostatin was administered at 6 h post-MCAO then at 3, 6, 9, 12, 15, and 18 d after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 d after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 d post-MCAO. Histological assessment of PKC isozymes was performed at 24 h post-MCAO. Results Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 d. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 d post-MCAO. Changes in PKC alpha expression and PKC epsilon expression in neurons were noted in bryostatin-treated rats at 24 h post-MCAO. Conclusions Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome following MCAO. PMID:24172582

  14. 5?-Reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in rats.

    PubMed

    Brunton, Paula J; Donadio, Marcio V; Yao, Song T; Greenwood, Mike; Seckl, Jonathan R; Murphy, David; Russell, John A

    2015-01-14

    Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1?; IL-1?) in adulthood, compared with controls. IL-1? acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3?-androstanediol (3?-diol; 5?-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the "programmed" hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1? (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3?-diol normalized HPA axis responses to IL-1? in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5?-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5?-reductase and 3?-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1?. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5?-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner. PMID:25589761

  15. 5?-Reduced Neurosteroids Sex-Dependently Reverse Central Prenatal Programming of Neuroendocrine Stress Responses in Rats

    PubMed Central

    Donadio, Marcio V.; Yao, Song T.; Greenwood, Mike; Seckl, Jonathan R.; Murphy, David; Russell, John A.

    2015-01-01

    Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1?; IL-1?) in adulthood, compared with controls. IL-1? acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3?-androstanediol (3?-diol; 5?-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the “programmed” hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1? (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3?-diol normalized HPA axis responses to IL-1? in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5?-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5?-reductase and 3?-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1?. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5?-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner. PMID:25589761

  16. Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages

    Microsoft Academic Search

    Valérie Boutard; Bruno Fouqueray; Carole Philippe; Joëlle Perez; Laurent Baud

    1994-01-01

    Fish oil supplementation and essential fatty acid deficiency reduce nitric oxide synthesis by rat macrophages. Both fish oil-derived ?-3 polyunsaturated fatty acid (?3 PUFA) supplementation and essential fatty acid (EFA) deficiency have been shown to exert anti-inflammatory effects and, hence, to ameliorate immune-mediated glomerulonephritis. The mechanisms underlying these effects include alterations in the production of eicosanoids, cytokines (that is, tumor

  17. L-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats

    Microsoft Academic Search

    G. N. Jyothirmayi; R. Modak; A. S. Reddi

    2001-01-01

    In this study, we examined the hypothesis whether exogenous administration of L-lysine in drinking water would reduce nonenzymatic glycation of glomerular basement membrane (GBM) collagen and thus albuminuria in streptozotocin-diabetic rats. The rationale is that the administered lysine would combine with the circulating glucose and make it unavailable to react with ε-amino groups of lysine of various proteins in these

  18. Macelignan attenuates LPS-induced inflammation and reduces LPS-induced spatial learning impairments in rats

    Microsoft Academic Search

    Chun-Ai Cui; Da-Qing Jin; Yoo Kyeong Hwang; Im-Soon Lee; Jae Kwan Hwang; Ilho Ha; Jung-Soo Han

    2008-01-01

    Previous studies have shown that macelignan has anti-inflammatory and neuroprotective effects. Subsequently, in the current study, we demonstrate that oral administrations of macelignan reduce the hippocampal microglial activation induced by chronic infusions of lipopolysaccharide (LPS) into the fourth ventricle of Fisher-344 rat brains. A Morris water maze was used to evaluate the status of the hippocampal-dependent spatial learning in control

  19. Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats

    Microsoft Academic Search

    Francesco Leri; Lindsay H. Burns

    2005-01-01

    Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague–Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg\\/kg\\/infusion), but not slightly higher doses (10 and 100 pg\\/kg\\/infusion), enhanced oxycodone (0.1 mg\\/kg\\/infusion) intravenous self-administration, suggesting a reduced rewarding potency

  20. Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats

    Microsoft Academic Search

    M Lucke; G Schmidmaier; S Sadoni; B Wildemann; R Schiller; N. P Haas; M Raschke

    2003-01-01

    Antibiotic prophylaxis is a routine procedure in orthopedic surgery. Various local antibiotic delivery techniques are used to reduce bone- and soft tissue-related infection. The objective of this study was to evaluate the efficacy of a new biodegradable, gentamicin-loaded poly(d,l-lactide) (PDLLA) coating of orthopedic devices in preventing implant-related osteomyelitis. The medullary cavities of tibiae in 30 Sprague Dawley rats were contaminated

  1. Caspase Inhibitors Reduce Neuronal Injury After Focal but Not Global Cerebral Ischemia in Rats

    Microsoft Academic Search

    Hui Li; Frederick Colbourne; Ping Sun; Zonghang Zhao; Alastair M. Buchan

    2010-01-01

    Background and Purpose—Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat. Methods—Various regimens of z-VAD,

  2. beta Adrenergic Receptors in Aged Rat Brain: Reduced Number and Capacity of Pineal Gland to Develop Supersensitivity

    Microsoft Academic Search

    Louise H. Greenberg; Benjamin Weiss

    1978-01-01

    The density but not the affinity of beta -adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be

  3. Essential fatty acid deficiency reduces cortical spreading depression propagation in rats: a two-generation study.

    PubMed

    Borba, Juliana Maria Carrazzone; Rocha-de-Melo, Ana Paula; dos Santos, Angela Amâncio; da Costa, Belmira Lara da Silveira Andrade; da Silva, Reginaldo Pereira; Passos, Priscila Pereira; Guedes, Rubem Carlos Araújo

    2010-06-01

    Cortical spreading depression (CSD) propagation was investigated in rats under dietary essential fatty acid (EFA) deficiency over two generations (F1 and F2). Wistar rat dams received diets containing 5% fat either from coconut-oil (EFA-deficient) or soybean-oil (control). F1-pups received their dams' diets until the day of CSD recording (30-40 days or 90-100 days). F2-pups were kept on their F1 dams' diet until 30-40 days. Compared to the controls, the EFA-deficient group had reduced (P < 0.05) body weights in both F1 and F2 conditions. This effect was more conspicuous (P < 0.001) in the F2-animals where brain weight was also reduced (P < 0.05). All EFA-deficient groups displayed lower CSD velocities (P < 0.001) than the corresponding controls. Within the same dietary group and generation, F1 young rats showed higher CSD velocities (P < 0.001) than adults. Data show that EFA deficiency reduces CSD propagation, and this effect is long lasting as it persists up to the second generation. PMID:20423564

  4. Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.

    PubMed

    De Paulis, Damien; Chiari, Pascal; Teixeira, Geoffrey; Couture-Lepetit, Elisabeth; Abrial, Maryline; Argaud, Laurent; Gharib, Abdallah; Ovize, Michel

    2013-09-01

    We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion. PMID:23955512

  5. Estradiol selectively reduces central neural activation induced by hypertonic NaCl infusion in ovariectomized rats.

    PubMed

    Jones, Alexis B; Bass, Eryn E; Fan, Liming; Curtis, Kathleen S

    2012-09-10

    We recently reported that the latency to begin drinking water during slow, intravenous infusion of a concentrated NaCl solution was shorter in estradiol-treated ovariectomized rats compared to oil vehicle-treated rats, despite comparably elevated plasma osmolality. To test the hypothesis that the decreased latency to begin drinking is attributable to enhanced detection of increased plasma osmolality by osmoreceptors located in the CNS, the present study used immunocytochemical methods to label fos, a marker of neural activation. Increased plasma osmolality did not activate the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), or the nucleus of the solitary tract (NTS) in either oil vehicle-treated rats or estradiol-treated rats. In contrast, hyperosmolality increased fos labeling in the area postrema (AP), the paraventricular nucleus of the hypothalamus (PVN) and the rostral ventrolateral medulla (RVLM) in both groups; however, the increase was blunted in estradiol-treated rats. These results suggest that estradiol has selective effects on the sensitivity of a population of osmo-/Na(+)-receptors located in the AP, which, in turn, alters activity in other central areas associated with responses to increased osmolality. In conjunction with previous reports that hyperosmolality increases blood pressure and that elevated blood pressure inhibits drinking, the current findings of reduced activation in AP, PVN, and RVLM-areas involved in sympathetic nerve activity-raise the possibility that estradiol blunts HS-induced blood pressure changes. Thus, estradiol may eliminate or reduce the initial inhibition of water intake that occurs during increased osmolality, and facilitate a more rapid behavioral response, as we observed in our recent study. PMID:22763321

  6. Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

    PubMed

    Nakamura, A; Suzuki, Y; Umegaki, H; Ikari, H; Tajima, T; Endo, H; Iguchi, A

    2001-12-01

    We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed. PMID:11786247

  7. Artichoke leaf extract reduces oxidative stress and lipoprotein dyshomeostasis in rats fed on high cholesterol diet.

    PubMed

    Küskü-Kiraz, Z; Mehmetçik, G; Dogru-Abbasoglu, S; Uysal, M

    2010-04-01

    Hypercholesterolemia and lipid peroxidation play complementary role in atherosclerosis. Artichoke leaf extract (ALE) is rich in natural antioxidants and has a cholesterol-reducing effect. However, there is no study investigating the effect of ALE on lipid levels and lipid peroxidation in experimental hypercholesterolemic conditions. Rats were fed on 4% (w/w) cholesterol and 1% (w/w) cholic acid supplemented diet for 1 month. ALE (1.5 g/kg/day) was given by gavage during the last 2 weeks. Serum lipid composition, malondialdehyde (MDA) and diene conjugate (DC) levels and plasma antioxidant activity (AOA) were measured. In addition, endogenous DC and copper-induced MDA levels were determined in apo B-containing lipoproteins (LDL+VLDL fraction). Serum cholesterol and triglyceride levels and the ratio of cholesterol to HDL-cholesterol decreased due to ALE treatment in rats fed on HC diet. Significant decreases in serum MDA and DC levels and increases in plasma AOA were detected in serum in ALE-treated hypercholesterolemic rats. Endogenous DC and copper-induced MDA levels were also lower in LDL+VLDL fraction due to ALE-treatment in hypercholesterolemic rats. Our results indicate that ALE may be useful for the prevention of hypercholesterolemia-induced pro-oxidant state in LDL+VLDL fraction and the reduction of increased serum cholesterol and triglyceride levels. PMID:19777605

  8. Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats

    Microsoft Academic Search

    Ryosuke Shiraishi; Takehiro Fujise; Tsukasa Kuroki; Takashi Kakimoto; Lujie Miao; Yasuhisa Sakata; Seiji Tsunada; Takahiro Noda; Ryuichi Iwakiri; Kazuma Fujimoto

    2009-01-01

    Purpose  We have shown previously that long-term feeding of beef tallow increases colorectal cancer in rats. This study investigated\\u000a the effects of enzymic antioxidant, reduced glutathione (GSH), on colon carcinogenesis in rats fed with beef tallow.\\u000a \\u000a \\u000a \\u000a Methods  Colon carcinogenesis was induced by intraperitoneal injection of azoxymethane (AOM) to rats. Rats were fed with 10% beef tallow\\u000a supplemented with or without 1% GSH

  9. Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

    Microsoft Academic Search

    M. M. Mahfouz; F. A. Kummerow

    2005-01-01

    The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and

  10. Environments predicting intermittent shortening access reduce operant performance but not home cage binge size in rats

    PubMed Central

    Wojnicki, F.H.E.; Babbs, R.K.; Corwin, R.L.W

    2013-01-01

    When non-food-deprived rats are given brief access to vegetable shortening (a semi-solid fat used in baked products) on an intermittent basis (Monday, Wednesday, Friday), they consume significantly more and emit more operant responses for shortening than a separate group of rats given brief access to shortening every day. Since both groups are traditionally housed in the same room, it is possible that the environmental cues associated with placing shortening in the cages (e.g., investigator in room, cages opening and closing, etc.) provide predictable cues to the daily group, but unpredictable cues to the intermittent group. The present study examined the effects of providing predictable environmental cues to an isolated intermittent group in order to examine the independent contributions of intermittency and predictability on intake and operant performance. Two groups of rats were housed in the same room, with one group provided 30-min intermittent (INT) access and the second group provided 30-min daily access (D) to shortening. A third group (ISO) of rats was housed in a room by themselves in which all environmental cues associated with intermittent shortening availability were highly predictable. After five weeks of home cage shortening access, all rats were then exposed to several different operant schedules of reinforcement. The INT and ISO groups consumed significantly more shortening in the home cage than the D group. In contrast, the INT group earned significantly more reinforcers than both the ISO and D groups under all but one of the reinforcement schedules, while ISO and D did not differ. These data indicate that intermittent access will generate binge-type eating in the home cage independent of cue predictability. However, predictable cues in the home cage reduce operant responding independent of intermittent access. PMID:23535243

  11. Dietary manipulations of body fat-reducing potential of conjugated linoleic acid in rats.

    PubMed

    Sugano, M; Akahoshi, A; Koba, K; Tanaka, K; Okumura, T; Matsuyama, H; Goto, Y; Miyazaki, T; Murao, K; Yamasaki, M; Nonaka, M; Yamada, K

    2001-11-01

    To study whether the body fat-reducing potential of conjugated linoleic acid (CLA) could be increased through dietary manipulations, the effects of the combination of CLA with different proteins, fats, and sesamin were examined in rats. Male rats were fed diets containing 1% CLA or linoleic acid (LA) in combination with different proteins (20% of casein or soybean protein), fats (7% perilla oil or soybean oil) and 0.2% sesamin (SES) for 3 or 4 weeks. When the dietary fat source was soybean oil, CLA, as compared with LA, significantly reduced weights of epididymal and perirenal adipose tissues, irrespective of the dietary protein sources. However, the highest reducing effect was shown when soybean protein was given as a protein source. SES stimulated the reduction of epididymal and perirenal adipose tissue weights in both protein diets. In contrast, CLA increased the weight of brown adipose tissue, and SES further increased it in combination with soybean oil but not with perilla oil. No effect of dietary manipulation was observed on serum leptin and TNF-alpha levels. Thus, the body fat-reducing potential of CLA can be increased by an appropriate combination with food factors that may stimulate fatty acid beta-oxidation. PMID:11791729

  12. Syzigium cumini seed extracts reduce tissue damage in diabetic rat brain.

    PubMed

    Stanely Mainzen Prince, P; Kamalakkannan, N; Menon, Venugopal P

    2003-02-01

    Syzigium cumini commonly known as Jamun, is widely used in different parts of India for the treatment of diabetes mellitus. Oral administration of an aqueous Jamun seed extract (JSEt) for 6 weeks caused a significant decrease in lipids, thiobarbituric acid reactive substances (TBARS) and an increase in catalase and superoxide dismutase in the brain of alloxan induced diabetic rats. Oral administration of an alcoholic JSEt for 6 weeks brought back all the parameters to near normal. The effect of alcoholic JSEt (100 mg/kg) was better than aqueous JSEt (5 g/kg). The effect of both these extracts was better than glibenclamide (600 microg/kg). Thus, our study shows that S. cumini seed extracts reduce tissue damage in diabetic rat brain. PMID:12648817

  13. Aqueous extract of Ficus religiosa linn. reduces oxidative stress in experimentally induced type 2 diabetic rats.

    PubMed

    Kirana, H; Agrawal, S S; Srinivasan, B P

    2009-10-01

    One of the major etiologies in pathogenesis of type 2 diabetes especially complications is oxidative stress. Aqueous extract of Ficus religiosa at a dose of 100 and 200 mg/kg orally decreased the fasting blood glucose in streptozotocin induced type 2 diabetic rats. The drug had enzyme induction effect with respect to catalase (CAT) and glutathione peroxidase (GSH-Px) activity, however decreased the exaggerated activity of superoxide dismutase (SOD) in type 2 diabetic rats. F. religiosa modulated the enzymes of antioxidant defence system to combat oxidative stress. As a result, glutathione (GSH-reduced form) was restored and inhibited the formation of malondialdehyde. Drug at higher dose (200 mg/kg) had more pronounced effect. F. religiosa, a rasayana group of plant drug having anti-diabetic activity along with antioxidant potential was beneficial in treatment of type 2 diabetes. PMID:20112810

  14. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    PubMed

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1?/?, peroxisome proliferator-activated receptor (PPAR)-?, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-?, fatty acid synthase (FAS) and PPAR? genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-?] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1?/? and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. PMID:24486395

  15. Aged male rats regenerate cortical bone with reduced osteocyte density and reduced secretion of nitric oxide after mechanical stimulation.

    PubMed

    Joiner, Danese M; Tayim, Riyad J; McElderry, John-David; Morris, Michael D; Goldstein, Steven A

    2014-05-01

    Mechanical loading is integral to the repair of bone damage. Osteocytes are mechanosensors in bone and participate in signaling through gap junction channels, which are primarily comprised of connexin 43 (Cx43). Nitric oxide (NO) and prostaglandin E2 (PGE2) have anabolic and catabolic effects on bone, and the secretion of these molecules occurs after mechanical stimulation. The effect of age on the repair of bone tissue after damage and on the ability of regenerated bone to transduce mechanical stimulation into a cellular response is unexplored. The goal of this study was to examine (1) osteocytes and their mineralized matrix within regenerated bone from aged and mature animals and (2) the ability of regenerated bone explants from aged and mature animals to transduce cyclic mechanical loading into a cellular response through NO and PGE2 secretion. Bilateral cortical defects were created in the diaphysis of aged (21-month-old) or mature (6-month-old) male rats, and new bone tissue was allowed to grow into a custom implant of controlled geometry. Mineralization and mineral-to-matrix ratio were significantly higher in regenerated bone from aged animals, while lacunar and osteocyte density and phosphorylated (pCx43) and total Cx43 protein were significantly lower, relative to mature animals. Regenerated bone from mature rats had increased pCx43 protein and PGE2 secretion with loading and greater NO secretion relative to aged animals. Reduced osteocyte density and Cx43 in regenerated bone in aged animals could limit the establishment of gap junctions as well as NO and PGE2 secretion after loading, thereby altering bone formation and resorption in vivo. PMID:24370615

  16. Reduced clearance of proteins labeled with diisopropylfluorophosphate in portacaval-shunted rats.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2014-12-01

    Portacaval shunting is a model for hepatic encephalopathy that causes chronic hyperammonemia, disruption of metabolic, signaling, and neurotransmitter systems, and progressive morphological changes. Exposure of cultured cells to ammonia raises intralysosomal pH and inhibits proteolysis, and the present study tested the hypothesis that proteolytic capacity is diminished in portacaval-shunted rats. Proteins were labeled in vivo with tracer doses of diisopropylfluorophosphate (DFP) and clearance of label was assayed. This approach labeled proteins independent of protein synthesis, which is reported to be altered in shunted rats, and avoided complications arising from re-utilization of labeled amino acids that causes underestimation of degradation rate. Characterization of DFP labeling showed that protein labeling was fast, about 50% of the label was released during a 24 h interval, labeling by DFP metabolites was negligible, inhibition of brain acetylcholinesterase was not detectable, and labeling by [(3)H]- and [(14)C]DFP was equivalent. To assay degradative capacity, proteins were first labeled with [(3)H]DFP, followed by labeling with [(14)C]DFP that was given 24 or 72 h later. The (3)H/(14)C ratio in each animal was used as a relative measure of removal of (3)H-labeled proteins. (3)H/(14)C ratios were generally significantly higher in portacaval-shunted rats than in controls, consistent with reduced proteolytic capacity. Assays of amino acid incorporation into brain protein generally replicated literature reports, supporting the conclusion that protein synthesis unlikely to be markedly inhibited and amino acid recycling influences calculated protein synthesis rates in shunted rats. Therapeutic strategies to reduce ammonia level would help normalize lysosomal functions and protein and lipid turnover. PMID:24154686

  17. Reduced Na-K-Cl cotransport in vascular smooth muscle cells from spontaneously hypertensive rats

    SciTech Connect

    O'Donnell, M.E.; Owen, N.E. (Chicago Medical School, IL (USA))

    1988-08-01

    The authors have previously demonstrated the presence of a prominent, cyclic nucleotide-sensitive Na-K-Cl cotransport in vascular smooth muscle cells (VSMC). Others have observed that Na-K-Cl cotransport levels are reduced in erythrocytes of patients with essential hypertension and have proposed that a defect in this Na transport system may play a role in the pathogenesis of the disease. However, such a defect has not been demonstrated in the putative target tissue for essential hypertension, i.e., the VSMC. In the present study, they compared Na-K-Cl cotransport of VSMC from spontaneously hypertensive rats (SHR) with Na-K-Cl cotransport of VSMC from normotensive Wistar-Kyoto rats (WKY). They found that Na-K-Cl cotransport of SHR VSMC is significantly reduced relative to that of WKY VSMC. The apparent ion affinities for Na-K-Cl cotransport of SHR VSMC did not differ from those determined for WKY VSMC. Furthermore, cyclic nucleotide regulation of cotransport also appeared to be the same for the two types of VSMC. In contrast, maximal saturable binding of ({sup 3}H)bumetanide observed in SHR VSMC was markedly reduced compared with that of WKY VSMC, but the K{sub d} values were similar. The data suggest that the reduction in cotransport observed in SHR VSMC is the result of a decrease in the number of available cotransport sites.

  18. Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

    PubMed

    Passos, Clévia Santos; Carvalho, Lucimeire Nova; Pontes, Roberto Braz; Campos, Ruy Ribeiro; Ikuta, Olinda; Boim, Mirian Aparecida

    2012-02-01

    The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus. PMID:22309003

  19. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    NASA Technical Reports Server (NTRS)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  20. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus

    PubMed Central

    Rock, E M; Kopstick, R L; Limebeer, C L; Parker, L A

    2013-01-01

    BACKGROUND AND PURPOSE We evaluated the anti-emetic and anti-nausea properties of the acid precursor of ?9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. EXPERIMENTAL APPROACH We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). KEY RESULTS In rats, THCA (0.05 and/or 0.5 mg·kg?1) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg?1) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg?1) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. CONCLUSIONS AND IMPLICATIONS THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting. PMID:23889598

  1. Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats

    Microsoft Academic Search

    Jen-Tsung Yang; Tsong-Hai Lee; I-Neng Lee; Chiu-Yen Chung; Chia-Hui Kuo; Hsu-Huei Weng

    Background  The molecular mechanism of hemorrhagic stroke is unclear, and the identification of therapeutic agents for attenuating post-stroke\\u000a brain damage remains an unresolved challenge. Dexamethasone (DEX) is used clinically to treat spinal cord injury and brain\\u000a tumor patients by reducing edema formation, but has produced conflicting results in stroke management.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In this study, intracerebral hemorrhage (ICH) was induced in rats by

  2. Triptolide (TPL) improves locomotor function recovery in rats and reduces inflammation after spinal cord injury.

    PubMed

    Wang, Bing; Chen, Chen; Zhang, Jing-Tao; Song, Ruo-Xian; Yu, Xiu-Chun

    2015-05-01

    In this study, we studied the effect of triptolide (TPL) on locomotor function in rats with spinal cord injury. A total of 40 rats were studied after dividing them in two major groups, one was experimental group denoted as TPL group while other was control group denoted as PBS group. Each group was subdivided in four subgroups having five rats each (n = 5). TPL was given intraperitonially at the rate of 5 mg/kg/day in TPL group while PBS was given at the same time interval in the same manner in control group for comparison. A reduction in the cavity area of tissue sections was observed by bright field microscopy from 0.22 ± 0.05 to 0.12 ± 0.05 mm(2) in experimental group after 28 days of treatment while BBB score also improved from 1 to 5 after 14 days of treatment. SPSS software, one way ANOVA, was used for recording statistical analysis and values were expressed as mean ± SEM where P value of <0.01 was considered significant. The expression of I-kB? and NF-kB p65 was also studied using western blotting and after recording optical density (OD) values of western blots. It was observed that treatment with TPL significantly reduced the expression of these factors after 28 days of treatment compared with controls. PMID:25547329

  3. Effect of Alocasia indica tuber extract on reducing hepatotoxicity and liver apoptosis in alcohol intoxicated rats.

    PubMed

    Pal, Swagata; Bhattacharjee, Ankita; Mukherjee, Sandip; Bhattacharya, Koushik; Mukherjee, Soumya; Khowala, Suman

    2014-01-01

    The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3 g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), ?-glutamyl transpeptidase (?-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33 min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect. PMID:24977149

  4. Effect of Alocasia indica Tuber Extract on Reducing Hepatotoxicity and Liver Apoptosis in Alcohol Intoxicated Rats

    PubMed Central

    Bhattacharya, Koushik; Mukherjee, Soumya

    2014-01-01

    The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3?g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), ?-glutamyl transpeptidase (?-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33?min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect. PMID:24977149

  5. Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

    PubMed

    Osman, Neamt H A; Said, Usama Z; El-Waseef, Ahmed M; Ahmed, Esraa S A

    2015-02-01

    Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone. PMID:25342594

  6. Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats

    PubMed Central

    Smeltzer, Michael; Scott, Karen; Melhorn, Susan; Krause, Eric

    2012-01-01

    During recovery from social stress in a visible burrow system (VBS), during which a dominance hierarchy is formed among the males, rats display hyperphagia and gain weight preferentially as visceral adipose tissue. By proportionally increasing visceral adiposity, social stress may contribute to the establishment of metabolic disorder. Amylin was administered to rats fed ad libitum during recovery from VBS stress in an attempt to prevent hyperphagia and the resultant gain in body weight and fat mass. Amylin treatment reduced food intake, weight gain, and accumulation of fat mass in male burrow rats, but not in male controls that spent time housed with a single female rather than in the VBS. Amylin did not alter neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of the hypothalamus as measured at the end of the recovery period, nor did it affect plasma corticosterone or leptin. Amylin exerted most of its effect on food intake during the first few days of recovery, possibly through antagonism of NPY and/or increasing leptin sensitivity. The potential for chronic social stress to contribute to metabolic disorder is diminished by amylin treatment, though the neuroendocrine mechanisms behind this effect remain elusive. PMID:22832535

  7. Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury.

    PubMed

    Walker, Chandler L; Walker, Melissa J; Liu, Nai-Kui; Risberg, Emelie C; Gao, Xiang; Chen, Jinhui; Xu, Xiao-Ming

    2012-01-01

    Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal cord injury, and sheds light on the signaling involved in its action. PMID:22253859

  8. Brown Norway Chromosome 1 Congenic Reduces Symptoms of Renal Disease in Fatty Zucker Rats

    PubMed Central

    Warden, Craig H.; Slupsky, Carolyn; Griffey, Stephen M.; Bettaieb, Ahmed; Min, Esther; Le, Anh; Fisler, Janis S.; Hansen, Susan; Haj, Fawaz; Stern, Judith S.

    2014-01-01

    We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by 1H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9–24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age. PMID:24498189

  9. Reduced oxygen consumption precedes the drop in body core temperature caused by hemorrhage in rats.

    PubMed

    Henderson, R A; Whitehurst, M E; Morgan, K R; Carroll, R G

    2000-01-01

    This study examines the early time course in core temperature change and oxygen consumption at 4 levels of hemorrhage. Chronically instrumented rats were acclimatized to a respirometry chamber for 30 min. The rats were briefly (10 min) removed from the chamber for a fixed volume hemorrhage of 0 mL/kg (sham), 8 mL/kg, 16 mL/kg, 24 mL/kg, or 32 mL/kg. Rats were then returned to the chamber, and oxygen consumption and body core temperature were monitored for the next 2 h. Oxygen consumption (control 1.26 mL O2/g/h) fell significantly 5 min after hemorrhage in all but the sham and 8 mL/kg hemorrhage groups, with the decrease proportional to the hemorrhage volume. The 32 mL/kg hemorrhage group showed the greatest decrease, to 0.47 mL O2/g/h. Body core temperature (control 37.5 degrees C) fell more gradually, declining to 35.6 degrees C 110 min after the 24 mL/kg hemorrhage, and to 33.2 degrees C at 6 h after the 32 mL/kg hemorrhage. In the 16 mL/kg hemorrhage group, oxygen consumption fell significantly by 5 min after hemorrhage, but a drop in body temperature was not seen until 25 min after hemorrhage. The data from this study indicate that the drop in core temperature does not cause the observed decrease in oxygen consumption. In fact, the timing and magnitude of the drop in oxygen consumption indicate that the reduced metabolic rate may mediate the hemorrhage-induced drop in body core temperature in conscious rats. PMID:10774622

  10. Human Interleukin-10 Gene Transfer Is Protective in a Rat Model of Parkinson’s Disease

    PubMed Central

    Johnston, Louisa C; Su, Xiaomin; Maguire-Zeiss, Kathleen; Horovitz, Karen; Ankoudinova, Irina; Guschin, Dmitry; Hadaczek, Piotr; Federoff, Howard J; Bankiewicz, Krystof; Forsayeth, John

    2009-01-01

    In Parkinson’s disease (PD) chronic inflammation occurs in the substantia nigra (SNc) concurrently with dop-aminergic neurodegeneration. In models of PD, microglial activation precedes neurodegeneration in the SNc, suggesting that the underlying pathogenesis involves a complex response in the nigrostriatal pathway, and that the innate immune system plays a significant role. We have investigated the neuroprotective effect of an ade-no-associated viral type-2 (AAV2) vector containing the complementary DNA (cDNA) for human interleukin-10 (hIL-10) in the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD. AAV2-hIL-10 reduced the 6-OHDA-induced loss of tyrosine hydroxylase (TH)-positive neurons in the SNc, and also reduced loss of striatal dopamine (DA). Pretreatment with AAV2-hIL-10 reduced glial activation in the SNc but did not attenuate striatal release of the inflammatory cytokine IL-1?. Assessment of rotational behavior in response to apomorphine challenge showed absence of asymmetry, confirming protection of dopaminergic innervation of the lesioned striatum. At baseline, 6-OHDA-lesioned animals displayed a deficit in contralateral forelimb use, but pretreatment with AAV2-hIL-10 reduced this forelimb akinesia. Transcriptional analyses revealed alteration of a few genes by AAV2-hIL-10; these alterations may contribute to neuroprotection. This study supports the need for further investigations relating to gene therapies aimed at reducing neuroinflammation in early PD. PMID:18545225

  11. Saffron Reduced Toxic Effects of its Constituent, Safranal, in Acute and Subacute Toxicities in Rats

    PubMed Central

    Ziaee, Toktam; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2014-01-01

    Background: Saffron and its constituents are widely used around the world as a spice and medicinal plant. Different constituents in medicinal herbs are thought to have the potential to induce useful and/or adverse effects. So, efforts have been made to find the best and most valuable tools to reduce their adverse effects. Objectives: According to Iranian traditional medicine (ITM), it is believed that administration of whole herbs exhibits more activity and fewer side effects than isolated constituents. Since toxicological studies have indicated that safranal is more toxic than other active components in saffron stigma, thus this study was undertaken to evaluate the effect of co-administration of saffron extract and safranal in acute and sub-acute toxicities in rats. Materials and Methods: In acute toxicity, rats received safranal (1.2 mL/kg, IP) plus saffron aqueous extract (25-100 mg/kg, IP). One and four days after the treatment, percentage of mortality was assessed. In subacute toxicity, rats were randomly divided into six groups. Group 1) safranal (0.2 mL/kg, IP), Groups 2, 3 and 4) safranal plus saffron aqueous extract (5, 10 and 20 mg/kg, IP) Groups 5 and 6) Paraffin and normal saline, as solvents of safranal and saffron aqueous extract, respectively. Treatments were continued for 21 days. For sub-acute toxicity, the percentages of lethality as well as some biochemical parameters were evaluated. Results: Our results showed that four days co-treatment of safranal and saffron significantly reduced mortality, so that the effect was more obvious in lower doses. Sub-acute toxicity studies showed that saffron could increase survival in rats so that no mortality was observed at dose of 10 mg/kg. Our data also indicated that the levels of triglyceride, BUN and ALT significantly increased after sub-acute interaperitoneal (IP) administration of safranal (0.2 mL/kg/day) and co-treatment of saffron aqueous extract (5 and 10 mg/kg) plus safranal significantly improved all toxic effects of safranal on biochemical parameters. Conclusions: The co-administration of saffron aqueous extract and safranal reduced toxic effects of safranal in acute and sub-acute toxicities. PMID:24644432

  12. Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression.

    PubMed

    Ren, Z H; Tong, Y H; Xu, W; Ma, J; Chen, Y

    2010-03-01

    The root of Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicine, has been used effectively for the treatment of cardiovascular diseases for a long time. The mechanisms underlying this therapeutic effect are not, however, fully understood. Tanshinone IIA (Tan IIA) is one of the major active components of this Chinese medicine. Therefore, the present study was performed to investigate whether Tan IIA, which has shown a cardio-protective capacity in myocardial ischemia, has an inhibitory effect on the inflammatory responses following myocardial infarction (MI) and its potential mechanisms. In an in vivo study, rat MI model was induced by permanent left anterior descending coronary artery (LAD) ligation. After the operation rats were divided into three groups (sham, MI and Tan IIA). Tan IIA was administered intragastrically at a dose of 60mg/kg body wt./day. One week later, rats were sacrificed and the hemodynamic, pathological and molecular biological indices were examined. In an in vitro study, the inflammatory model was established by TNF-alpha stimuli on cardiacmyocyte and cardiac fibroblasts. Tan IIA attenuates the MI pathological changes and improves heart function, and reduces expression of MCP-1, TGF-beta(1) and macrophage infiltration. Furthermore, Tan IIA could also decrease the expression of TNF-alpha and activation of nuclear transcription factor-kappa B (NF-kappaB). In vitro, Tan IIA could reduce MCP-1 and TGF-beta(1)secretion of cardiac fibroblasts. The present study demonstrated that the cardioprotective effects of Tan IIA might be attributed to its capacity for inhibiting inflammatory responses. PMID:19800776

  13. Alcohol Binge Drinking during Adolescence or Dependence during Adulthood Reduces Prefrontal Myelin in Male Rats

    PubMed Central

    Vargas, Wanette M.; Bengston, Lynn; Gilpin, Nicholas W.; Whitcomb, Brian W.

    2014-01-01

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism. PMID:25355229

  14. Melatonin reduces hippocampal beta-amyloid generation in rats exposed to chronic intermittent hypoxia.

    PubMed

    Ng, Kwong-Man; Lau, Chi-Fai; Fung, Man-Lung

    2010-10-01

    The deposition of neurotoxic beta-amyloid plaques plays a central role in the pathogenesis of Alzheimer's disease. At the molecular level, the generation of beta-amyloid peptides involves the site-specific cleavage of the precursor protein by beta-site APP cleavage enzyme (BACE) and presenilin. Although acute or chronic sustained hypoxia appears to increase the generation of beta-amyloid peptides via the HIF-1 alpha dependent upregulation of BACE, the effect of chronic intermittent hypoxia (CIH) on the generation of beta-amyloid peptides remains uncertain. In this study, we have evaluated such contention in the rat hippocampus, and we found that short-term CIH exposure (3 days) caused significant increases in the generation of beta-amyloid peptides, and the expressions of BACE, presenilin and HIF-1 alpha protein levels, in the hippocampus of CIH rats. Moreover, the CIH-induced hippocampal beta-amyloid peptide generation could be abolished by a daily pharmacological administration of melatonin (10mg/kg), which reduced the BACE but not presenilin expression. Also, there were no significant differences in the hippocampal HIF-1 alpha protein levels between the melatonin- and vehicle-treated CIH groups. Our study not only provided the first evidence that short-term CIH exposure could induce the beta-amyloid peptide generation in the hippocampus, but also pointed out the therapeutic value of melatonin in reducing beta-amyloid peptide generation in patients suffering from chronic obstructive sleep apnea syndrome. PMID:20654588

  15. Red yeast rice repairs kidney damage and reduces inflammatory transcription factors in rat models of hyperlipidemia.

    PubMed

    Ding, Mei; Si, Daoyuan; Zhang, Wenqi; Feng, Zhaohui; He, Min; Yang, Ping

    2014-12-01

    Xuezhikang (XZK), an extract of red yeast rice, has been widely used for the management of hyperlipidemia and coronary heart disease (CHD); however, the effects of XZK treatment on kidney injury have not yet been fully identified. The aim of the current study was to evaluate the effects of XZK on the kidneys and investigate the related mechanisms in a rat model of hyperlipidemia. Thus, the effect on inflammatory transcription factors and kidney damage was investigated with in vitro and in vivo experiments on hyperlipidemic rats following XZK treatment. The results revealed that the plasma levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased, while the levels of high-density lipoprotein-cholesterol (HDL-C) were significantly upregulated in the XZK treatment group, as compared with those in the hyperlipidemia group (P<0.05). In addition, the results demonstrated that XZK was able to repair the kidney damage caused by hyperlipidemia. Furthermore, the expression levels of the inflammatory transcription factors, tumor necrosis factor-? and interleukin-6, were shown to be reduced in the XZK group when compared with the hyperlipidemia group. In summary, XZK reduces kidney injury, downregulates the levels of TG, TC and LDL-C, as well as the expression levels of inflammatory transcription factors, and upregulates HDL-C. These results further the understanding of the molecular pathogenic mechanisms underlying hyperlipidemia and aid the development of XZK as an effective therapeutic agent for hyperlipidemia. PMID:25371725

  16. Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor.

    PubMed

    Calabrese, Francesca; Guidotti, Gianluigi; Racagni, Giorgio; Riva, Marco A

    2013-12-01

    Aging is a physiological process characterized by a significant reduction of neuronal plasticity that might contribute to the functional defects observed in old subjects. Even if the neurobiological mechanisms that contribute to such impairment remain largely unknown, a role for neurotrophic molecules, such as the neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On this basis, the purpose of this study was to provide a detailed investigation of the BDNF system, at transcriptional and translational levels, in the ventral and dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats, compared with in adult animals. The expression of major players in BDNF regulation and response, including the transcription factors, calcium-responsive transcription factor, cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed. Our results demonstrate that the BDNF system is affected at different levels in aged rats with global impairment including reduced transcription, impaired protein synthesis and processing, and decreased activation of the TrkB receptors. These modifications might contribute to the cognitive deficits associated with aging and suggest that pharmacological strategies aimed at restoring reduced neurotrophism might be useful to counteract age-related cognitive decline. PMID:23870838

  17. Inhaled nitric oxide reduces tyrosine nitration after lipopolysaccharide instillation into lungs of rats.

    PubMed

    Honda, K; Kobayashi, H; Hataishi, R; Hirano, S; Fukuyama, N; Nakazawa, H; Tomita, T

    1999-08-01

    Nitric oxide (NO) may either protect against or contribute to inflammatory lung injury. In this study we investigated whether inhalation of 20 ppm NO alters tyrosine nitration, and we assessed the degree of lung inflammation and edema in rats after lipopolysaccharide (LPS) instillation. The amount of nitrotyrosine relative to the total amount of tyrosine was measured in lung homogenates, and lung tissue sections were stained for nitrotyrosine and aminotyrosine (a reduced form of nitrotyrosine). Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, and myeloperoxidase activity was measured in lung homogenate. Lung edema and inflammatory cell accumulation in lung tissue were estimated by extravascular lung water weight (EVLW) and extravascular dry lung weight (EVDW), respectively. LPS instillation caused increases in nitrotyrosine concentration and immunohistochemical staining of nitrotyrosine and aminotyrosine in the lungs. LPS instillation increased the BALF leukocyte count, myeloperoxidase activity in lung tissue, and both EVLW and EVDW. Inhalational exposure to 20 ppm NO induced nitrotyrosine and aminotyrosine formation only in bronchial epithelial cell surface of the lungs not instilled with LPS. NO inhalation reduced the increases in nitrotyrosine and aminotyrosine in LPS-instilled lung tissue as well as the leukocyte count in BALF and myeloperoxidase activity in lung tissue, but it did not significantly change EVLW or EVDW. Leukocyte depletion in LPS-instilled rats reduced interstitial inflammatory cells, which were stained with nitrotyrosine and aminotyrosine, and attenuated the nitrotyrosine staining of alveolar capillaries. These results suggest that inhalation of 20 ppm NO reduces leukocyte accumulation in the lungs and inhibits tyrosine nitration caused by LPS instillation. PMID:10430746

  18. Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.

    PubMed

    Bao, Xiao-Chen; Chen, Hong; Fang, Yi-Qun; Yuan, Heng-Rong; You, Pu; Ma, Jun; Wang, Fang-Fang

    2015-06-01

    Inflammation and platelet activation are critical phenomena in the setting of decompression sickness. Clopidogrel (Clo) inhibits platelet activation and may also reduce inflammation. The goal of this study was to investigate if Clo had a protective role in decompression sickness (DCS) through anti-inflammation way. Male Sprague-Dawley rats (n=111) were assigned to three groups: control+vehicle group, DCS+vehicle, DCS+Clo group. The experimental group received 50mg/kg of Clo or vehicle for 3 days, then compressed to 1,600kPa (150msw) in 28s, maintained at 150msw for 242s and decompressed to surface at 3m/s. In a control experiment, rats were also treated with vehicle for 3 days and maintained at atmospheric pressure for an equivalent period of time. Clinical assessment took place over a period of 30min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine detection. The pathology and the wet/dry ratio of lung tissues, immunohistochemical detection of lung tissue CD41 expression, the numbers of P-selectin positive platelets and platelet-leukocyte conjugates in blood were tested. We found that Clo significantly reduced the DCS mortality risk (mortality rate: 11/45 with Clo vs. 28/46 in the untreated group, P<0.01). Clo reduced the lung injury, the wet/dry ratio of lung, the accumulation of platelet and leukocyte in lung, the fall in platelet count, the WBC count, the numbers of activated platelets and platelet-leukocyte complexes in peripheral blood. It was concluded that Clo can play a protective role in decompression sickness through reducing post-decompression platelet activation and inflammatory process. PMID:25784626

  19. Factors affecting the ability of baclofen to reduce fat intake in rats.

    PubMed

    Wojnicki, Francis H E; Brown, Shane D; Corwin, Rebecca L W

    2014-04-01

    The GABA-B agonist baclofen has been reported to reduce the consumption of vegetable shortening, but not lard, in rats. This study sought to examine some of the factors that could account for these differences. Baclofen (0, 1.0, 1.8, 3.2 mg/kg, intraperitoneal) was tested: (i) on shortening and lard intake, (ii) under 'binge-type' and non-'binge-type' conditions, (iii) when each fat was presented alone or simultaneously, and (iv) with a 30-min or no pretreatment time. With a 30-min pretreatment time, baclofen (3.2 mg/kg, intraperitoneal) consistently reduced shortening intake under 'binge-type' and non-'binge-type' conditions, as well as when shortening was presented alone or when lard was simultaneously available. Baclofen also reduced lard intake under 'binge-type' and non-'binge-type' conditions, but only when lard was presented alone. Baclofen had no effect on chow intake. When each fat was presented alone, and with no pretreatment time, the results were less consistent; baclofen reduced shortening intake only under non-'binge-type' conditions, and lard intake only under 'binge-type' conditions, and also stimulated chow intake. In summary, the type of fat, the presentation mode (one fat presented alone or two fats simultaneously), and the time between baclofen administration and intake all influence the ability of baclofen to reduce fat intake. PMID:24569221

  20. Perioperative Betamethasone Treatment Reduces Signs of Bladder Dysfunction in a Rat Model for Neurapraxia in Female Urogenital Surgery

    PubMed Central

    Castiglione, Fabio; Bergamini, Alice; Bettiga, Arianna; Bivalacqua, Trinity J.; Benigni, Fabio; Strittmatter, Frank; Gandaglia, Giorgio; Rigatti, Patrizio; Montorsi, Francesco; Hedlund, Petter

    2014-01-01

    Background Information on autonomic neurapraxia in female urogenital surgery is scarce, and a model to study it is not available. Objective To develop a model to study the impact of autonomic neurapraxia on bladder function in female rats, as well as to assess the effects of corticosteroid therapy on the recovery of bladder function in this model. Design, setting, and participants Female Sprague-Dawley rats were subjected to bilateral pelvic nerve crush (PNC) and perioperatively treated with betamethasone or vehicle. Bladder function and morphology of bladder tissue were evaluated and compared with sham-operated rats. Outcome measurements and statistical analysis Western blot, immunohistochemistry, organ bath experiments, and cystometry. Results and limitations Sham-operated rats exhibited regular micturitions without nonvoiding contractions (NVCs). Crush of all nerve branches of the pelvic plexus or PNC resulted in overflow incontinence and/or NVCs. Betamethasone treatment improved recovery of regular micturitions (87.5% compared with 27% for vehicle; p < 0.05), reduced lowest bladder pressure (8 ± 2 cm H2O compared with 21 ± 5 cm H2O for vehicle; p < 0.05), and reduced the amplitude of NVCs but had no effect on NVC frequency in PNC rats. Compared with vehicle, betamethasone-treated PNC rats had less CD68 (a macrophage marker) in the pelvic plexus and bladder tissue. Isolated bladder from betamethasone-treated PNC rats exhibited better nerve-induced contractions, contained more cholinergic and sensory nerves, and expressed lower amounts of collagen III than bladder tissue from vehicle-treated rats. Conclusions PNC causes autonomic neurapraxia and functional and morphologic changes of isolated bladder tissue that can be recorded as bladder dysfunction during awake cystometry in female rats. Perioperative systemic betamethasone treatment reduced macrophage contents of the pelvic plexus and bladder, partially counteracted changes in the bladder tissue, and had protective effects on micturition function. PMID:22542670

  1. A Horseradish Peroxidase Study of Motorneuron Pools of the Forelimb and Hindlimb Musculature of the Axolotl

    Microsoft Academic Search

    N. Stephens; N. Holder

    1985-01-01

    Motorneuron pools innervating axolotl limb muscles have been investigated by using the retrograde neuronal tracer horseradish peroxidase. Four muscles in the forelimb (biceps, anconeus, flexor digitorum and extensor digitorum) and four functionally equivalent muscles in the hindlimb (puboischiotibialis, iliotibialis, flexor digitorum and extensor digitorum) were studied. Motorneuron pools were characterized by using four criteria: position in the rostrocaudal axis; position

  2. Muscle moment arms and function of the siamang forelimb during brachiation

    E-print Network

    D'Aoűt, Kristiaan

    Muscle moment arms and function of the siamang forelimb during brachiation Fana Michilsens,1,2 Evie have an important modulating impact on muscle function, as they represent the capacity of the muscle to convert muscle action into limb movements. In the current paper, we provide muscle moment arm data

  3. The pattern of neurovascular development in the forelimb of the quail embryo.

    PubMed

    Bates, Damien; Taylor, G Ian; Newgreen, Donald F

    2002-09-15

    Peripheral nerve and vascular patterns are congruent in the adult vertebrate, but this has been disputed in vertebrate embryos. The most detailed of these studies have used the avian forelimb as a model system, yet neurovascular anatomical relationships and critical vascular remodeling events remain inadequately characterized in this model. To address this, we have used a combination of intravascular marker injection, multilabel fluorescent stereomicroscopy, and confocal microscopy to analyze the spatiotemporal relationships between peripheral nerves and blood vessels in the forelimb of 818 quail embryos from E2 (HH13) to E15 (HH41). We find that the neurovascular anatomical relationships established during development are highly stereotypic and congruent. Blood vessels typically arise before their corresponding nerves, but there are several critical exceptions to this rule. The vascular pattern is extensively remodeled from the earliest stage examined (E2; HH13), whereas the peripheral nerves, the first of which enter the forelimb at E3.5-E4 (HH21-HH24), have a progressively unfolding pattern that, once formed, remains essentially unchanged. The adult neurovascular pattern is not established until E8 (HH34). Peripheral nerves are always found to track close and parallel to the vasculature. As they track distally, peripheral nerves always lie on the side of the vasculature away from the center of the forelimb. Neurovascular patterns have a hierarchy of congruence that is highest in the dorsoventral plane, followed by the anteroposterior, and lastly the proximodistal planes. PMID:12221008

  4. Kinetics of the forelimb in horses circling on different ground surfaces at the trot.

    PubMed

    Chateau, Henry; Camus, Mathieu; Holden-Douilly, Laurčne; Falala, Sylvain; Ravary, Bérangčre; Vergari, Claudio; Lepley, Justine; Denoix, Jean-Marie; Pourcelot, Philippe; Crevier-Denoix, Nathalie

    2013-12-01

    Circling increases the expression of distal forelimb lameness in the horse, depending on rein, diameter and surface properties of the circle. However, there is limited information about the kinetics of horses trotting on circles. The aim of this study was to quantify ground reaction force (GRF) and moments in the inside and outside forelimb of horses trotting on circles and to compare the results obtained on different ground surfaces. The right front hoof of six horses was equipped with a dynamometric horseshoe, allowing the measurement of 3-dimensional GRF, moments and trajectory of the centre of pressure. The horses were lunged at slow trot (3 m/s) on right and left 4 m radius circles on asphalt and on a fibre sand surface. During circling, the inside forelimb produced a smaller peak vertical force and the stance phase was longer in comparison with the outside forelimb. Both right and left circling produced a substantial transversal force directed outwards. On a soft surface (sand fibre), the peak transversal force and moments around the longitudinal and vertical axes of the hoof were significantly decreased in comparison with a hard surface (asphalt). Sinking of the lateral or medial part of the hoof in a more compliant surface enables reallocation of part of the transversal force into a proximo-distal force, aligned with the limb axis, thus limiting extrasagittal stress on the joints. PMID:24511634

  5. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat

    Microsoft Academic Search

    Prabal K Chatterjee; Salvatore Cuzzocrea; Paul AJ Brown; Kai Zacharowski; Keith N Stewart; Helder Mota-Filipe; Christoph Thiemermann

    2000-01-01

    Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat.BackgroundThe generation of reactive oxygen species (ROS) contributes to the pathogenesis of renal ischemia-reperfusion injury. The aim of this study was to investigate the effects of tempol in (1) an in vivo rat model of renal ischemia\\/reperfusion injury and on (2) cellular injury and death of

  6. Noopept Reduces the Postischemic Functional and Metabolic Disorders in the Brain of Rats with Different Sensitivity to Hypoxia

    Microsoft Academic Search

    I. V. Zarubina; P. D. Shabanov

    2009-01-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to\\u000a hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg\\/kg) during 7 days after occlusion\\u000a of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved\\u000a their survival during the postischemic

  7. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    PubMed Central

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting. PMID:9202072

  8. Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model.

    PubMed

    Zaccaria, A; Weinzweig, N; Yoshitake, M; Matsuda, T; Cohen, M

    1994-12-01

    Free radicals have been implicated in the cause of ischemia-reperfusion injury. Various agents have been used in an attempt to reduce ischemia-reperfusion injury pharmacologically, including free radical scavengers. Vitamin C (ascorbic acid), a well-known free radical scavenger, has not, to the best of our knowledge, been evaluated in this respect. Previous work at our institution has shown that vitamin C decreases capillary permeability, thus significantly reducing fluid resuscitation requirements in postburn cases. Because this is due in part to the scavenging effect of vitamin C on free radicals, we investigated the role, if any, of vitamin C on ischemia-reperfusion injury in a rat epigastric island skin flap model. Twenty-four adult Sprague-Dawley rats were divided into control and vitamin C groups. Superficial epigastric island skin flaps measuring 6.0 x 3.5 cm were raised. Pedicles were isolated and occluded with microvascular clamps for 6 hours. The flaps were then sutured back to their beds over Steri-Drape barriers. Fifteen minutes before reperfusion, the control group flaps were perfused via femoral artery cannulation with normal saline (2.5 ml/kg). The vitamin C-treated group was perfused in a similar fashion with 2.5 ml/kg of a vitamin C/normal saline solution (27 mg/ml). The animals were observed for 7 days, and the percentage of flap survival was determined using a paper template technique. The vitamin C-treated group demonstrated a significantly higher percentage of flap survival than did the control group (25.8% mean vs. 7.5% mean, p < 0.025). In this animal model, vitamin C reduced or limited reperfusion injury after 6 hours of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7880053

  9. Linseed Dietary Fibers Reduce Apparent Digestibility of Energy and Fat and Weight Gain in Growing Rats

    PubMed Central

    Kristensen, Mette; Bach Knudsen, Knud Erik; Jřrgensen, Henry; Oomah, David; Bügel, Susanne; Toubro, Sřren; Tetens, Inge; Astrup, Arne

    2013-01-01

    Dietary fibers (DF) may affect energy balance, an effect often ascribed to the viscous nature of some water soluble DF, which affect luminal viscosity and thus multiple physiological processes. We have tested the hypothesis that viscous linseed DF reduce apparent nutrient digestibility, and limit weight gain, in a randomized feeding trial where 60 male, growing, Wistar rats, with an initial weight of ~200 g, were fed different diets (n = 10 per group): low DF control (C), 5% DF from cellulose (5-CEL), CEL + 5% DF from whole (5-WL) or ground linseed (5-GL), CEL + 5% DF from linseed DF extract (5-LDF), and CEL + 10% DF from linseed DF extract (10-LDF). Diets were provided ad libitum for 21 days. Feed intake and faecal output were measured during days 17–21. Faecal fat excretion increased with increasing DF content and was highest in the 10-LDF group. Apparent fat digestibility was highest with the C diet (94.9% ± 0.8%) and lowest (74.3% ± 0.6%) with the 10-LDF diet, and decreased in a non-linear manner with increasing DF (p < 0.001). Apparent fat digestibility also decreased with increased accessibility of DF (5-WL vs. 5-GL) and when the proportion of viscous DF increased (5-GL vs. 5-LDF). The 10-LDF resulted in a lower final body weight (258 ± 6.2 g) compared to C (282 ± 5.9 g), 5-CEL (281 ± 5.9 g), and 5-WL (285 ± 5.9 g) (p < 0.05). The 10-LDF diet reduced body fat compared to 5-CEL (p < 0.01). In conclusion, DF extracted from linseed reduced apparent energy and fat digestibility and resulted in restriction of body weight gain in growing rats. PMID:23966109

  10. From fish to modern humans – comparative anatomy, homologies and evolution of the pectoral and forelimb musculature

    PubMed Central

    Diogo, R; Abdala, V; Aziz, M A; Lonergan, N; Wood, B A

    2009-01-01

    In a recent study Diogo & Abdala [(2007) JMorphol268, 504–517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans. PMID:19438764

  11. Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats.

    PubMed

    Vonhoff, Christian; Baumgartner, Andreas; Hegger, Mirjam; Korte, Brigitte; Biller, Andreas; Winterhoff, Hilke

    2006-02-01

    Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations. Lycopus extract was tested in thyroxine treated hyperthyroid rats (0.7 mg/kg BW i.p.). Co-treatment with an hydroethanolic extract from L. europaeus L. started one week later than T4-application and lasted 5.5 weeks. As reference substance atenolol was used. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and the increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed. Lycopus extract and atenolol reduced the increased heart rate and blood pressure. The cardiac hypertrophy was alleviated significantly by both treatment regimes. beta-Adrenoceptor density in heart tissue was significantly reduced by the Lycopus extract or the beta-blocking agent showing an almost equal efficacy. Although the mode of action remains unclear, these organo-specific anti-T4-effects seem to be of practical interest, for example in patients with latent hyperthyroidism. PMID:16150466

  12. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease

    PubMed Central

    2011-01-01

    Background Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 is constitutively expressed. It is not known if addition of exogenous CX3CL1 beyond otherwise physiologically normal levels could decrease microglia activation and thereby minimize the secondary neurodegeration following a neurotoxic insult. Methods The intrastriatal 6-hydroxydopamine (6-OHDA) rat model of Parkinson disease, was used to test the hypothesis that exogenous CX3CL1 could be neuroprotective. Treatment with recombinant CX3CL1 was delivered to the striatum by an osmotic minipump for 28 days beginning 7 days after the initial insult. Unbiased stereological methods were used to quantify the lesion size in the striatum, the amount of neuronal loss in the substantia nigra, and the amount of microglia activation. Results As hypothesized, CX3CL1 was able to suppress this microglia activation. The reduced microglia activation was found to be neuroprotective as the CX3CL1 treated rats had a smaller lesion volume in the striatum and importantly significantly fewer neurons were lost in the CX3CL1 treated rats. Conclusion These findings demonstrated that CX3CL1 plays a neuroprotective role in 6-OHDA-induced dopaminergic lesion and it might be an effective therapeutic target for many neurodegenerative diseases, including Parkinson disease and Alzheimer disease, where inflammation plays an important role. PMID:21266082

  13. Complete forelimb myology of the basal theropod dinosaur Tawa hallae based on a novel robust muscle reconstruction method.

    PubMed

    Burch, Sara H

    2014-09-01

    The forelimbs of nonavian theropod dinosaurs have been the subject of considerable study and speculation due to their varied morphology and role in the evolution of flight. Although many studies on the functional morphology of a limb require an understanding of its musculature, comparatively little is known about the forelimb myology of theropods and other bipedal dinosaurs. Previous phylogenetically based myological reconstructions have been limited to the shoulder, restricting their utility in analyses of whole-limb function. The antebrachial and manual musculature in particular have remained largely unstudied due to uncertain muscular homologies in archosaurs. Through analysis of the musculature of extant taxa in a robust statistical framework, this study presents new hypotheses of homology for the distal limb musculature of archosaurs and provides the first complete reconstruction of dinosaurian forelimb musculature, including the antebrachial and intrinsic manual muscles. Data on the forelimb myology of a broad sample of extant birds, crocodylians, lizards, and turtles were analyzed using maximum likelihood ancestral state reconstruction and examined together with the osteology of the early theropod Tawa hallae from the Late Triassic of New Mexico to formulate a complete plesiomorphic myology for the theropod forelimb. Comparisons with previous reconstructions show that the shoulder musculature of basal theropods is more similar to that of basal ornithischians and sauropodomorphs than to that of dromaeosaurids. Greater development of the supracoracoideus and deltoideus musculature in theropods over other bipedal dinosaurs correlates with stronger movements of the forelimb at the shoulder and an emphasis on apprehension of relatively large prey. This emphasis is further supported by the morphology of the antebrachium and the intrinsic manual musculature, which exhibit a high degree of excursion and a robust morphology well-suited for powerful digital flexion. The forelimb myology of Tawa established here helps infer the ancestral conformation of the forelimb musculature and the osteological correlates of major muscle groups in early theropods. These data are critical for investigations addressing questions relating to the evolution of specialized forelimb function across Theropoda. PMID:25040486

  14. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium.

    PubMed

    Vassallo, D V; Lebarch, E C; Moreira, C M; Wiggers, G A; Stefanon, I

    2008-09-01

    Lead (Pb2+) poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g) before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 microM) to the bath. Changes in rate of stimulation (0.1-1.5 Hz), relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM), and the effect of isoproterenol (20 ng/mL) were determined before and after the addition of 100 microM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz) and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 microM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 microM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 microM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 microM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle. PMID:18820769

  15. Exposure to Perfluorooctane Sulfonate In Utero Reduces Testosterone Production in Rat Fetal Leydig Cells

    PubMed Central

    Zhao, Binghai; Li, Li; Liu, Jieting; Li, Hongzhi; Zhang, Chunlei; Han, Pengfei; Zhang, Yufei; Yuan, Xiaohuan; Ge, Ren Shan; Chu, Yanhui

    2014-01-01

    Background Perfluorooctane sulfonate (PFOS) is a synthetic material that has been widely used in industrial applications for decades. Exposure to PFOS has been associated with decreased adult testosterone level, and Leydig cell impairment during the time of adulthood. However, little is known about PFOS effects in utero on fetal Leydig cells (FLC). Methods and Results The present study investigated effects of PFOS on FLC function. Pregnant Sprague Dawley female rats received vehicle (0.05% Tween20) or PFOS (5, 20 mg/kg) by oral gavage from gestational day (GD) 11–19. At GD20, testosterone (T) production, FLC numbers and ultrastructure, testicular gene and protein expression levels were examined. The results indicate that exposures to PFOS have affected FLC function as evidenced by decreased T production, impaired FLC, reduced FLC number, and decreased steroidogenic capacity and cholesterol level in utero. Conclusion The present study shows that PFOS is an endocrine disruptor of male reproductive system as it causes reduction of T production and impairment of rat fetal Leydig cells. PMID:24454680

  16. Ruthenium red, but not capsazepine reduces plasma extravasation by cigarette smoke in rat airways.

    PubMed Central

    Geppetti, P.; Bertrand, C.; Baker, J.; Yamawaki, I.; Piedimonte, G.; Nadel, J. A.

    1993-01-01

    1. Cigarette smoke increases vascular permeability in rat airways by activating release of tachykinin from capsaicin-sensitive sensory nerves. However, the mechanism by which cigarette smoke induces secretion of sensory neuropeptides is unknown. Here we hypothesized that cigarette smoke activates sensory nerve endings via a mechanism similar to that of capsaicin. 2. We studied the effects of ruthenium red, an inorganic dye which blocks the cation influx promoted by capsaicin and of the capsaicin antagonist capsazepine on the increase in vascular permeability produced by cigarette smoke, capsaicin, hypertonic saline and substance P in the trachea of pentobarbitone anaesthetized rats. We also investigated the ability of cigarette smoke to desensitize sensory nerve fibres. 3. Ruthenium red (10 mM) by aerosol blocked the increase in vascular permeability induced by capsaicin (0.5 microM) and reduced the response to cigarette smoke (5 puffs) but did not affect responses evoked by hypertonic saline (7.2%) or by substance P (10 microM) (all given by aerosol). Aerosols of capsazepine (0.1 mM) prevented extravasation by capsaicin, but did not inhibit response to cigarette smoke, hypertonic saline or substance P. Finally, pre-exposure to a high dose of cigarette smoke (10 puffs) prevented the extravasation caused by cigarette smoke (5 puffs) itself and by intravenous capsaicin (150 micrograms kg-1), but not that by intravenous substance P (10 nmol kg-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682132

  17. Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats.

    PubMed

    Pirat, Arash; Zeyneloglu, Pinar; Aldemir, Derya; Yücel, Muammer; Ozen, Ozlem; Candan, Selim; Arslan, Gülnaz

    2006-01-01

    In this rat model study we evaluated whether pretreatment with simvastatin affects the severity of acute lung injury caused by intestinal ischemia-reperfusion (I/R). Twenty-four animals were randomly allocated to three equal groups (sham, control, simvastatin). The simvastatin group was pretreated with simvastatin 10 mg x kg(-1) x day(-1) for 3 days, whereas the other groups received placebo. The simvastatin and control groups underwent 60 min of superior mesenteric artery occlusion and 90 min of reperfusion. Compared with the simvastatin group, the control group exhibited significantly more severe intestinal I/R-induced acute lung injury, as indicated by lower Pao2 and oxygen saturation (P = 0.01 and P = 0.005, respectively) and higher mean values for neutrophil infiltration of the lungs (P = 0.003), total lung histopathologic injury score (P = 0.003), lung wet-to-dry weight ratio (P = 0.009), and lung-tissue malondialdehyde levels (P = 0.016). The control and simvastatin groups had similar serum levels and similar bronchoalveolar lavage fluid levels of cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and P-selectin at all measurements, except for a significantly higher level of bronchoalveolar lavage fluid P-selectin in the control group (P = 0.006). Pretreatment with simvastatin reduces the severity of acute lung injury induced by intestinal I/R in rats. PMID:16368834

  18. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B? exposure in rats and humans.

    PubMed

    Robinson, A; Johnson, N M; Strey, A; Taylor, J F; Marroquin-Cardona, A; Mitchell, N J; Afriyie-Gyawu, E; Ankrah, N A; Williams, J H; Wang, J S; Jolly, P E; Nachman, R J; Phillips, T D

    2012-01-01

    Fumonisin B? (FB?) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB? (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB? in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB? control, FB??+?2% NS or absolute control group. FB? alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3?g?day?ą) or placebo (1.5?g?day?ą) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB? biomarker by 20% in 24?h and 50% after 48?h compared to controls. In the humans, 56% of the urine samples analysed (n?=?186) had detectable levels of FB?. Median urinary FB? levels were significantly (p?90% in the high dose NS group (3?g?day?ą) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB? (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB?. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB? is suspected to be a dietary risk factor for HCC and oesophageal cancer in humans. PMID:22324939

  19. Oral administration of interferon tau enhances oxidation of energy substrates and reduces adiposity in Zucker diabetic fatty rats.

    PubMed

    Tekwe, Carmen D; Lei, Jian; Yao, Kang; Rezaei, Reza; Li, Xilong; Dahanayaka, Sudath; Carroll, Raymond J; Meininger, Cynthia J; Bazer, Fuller W; Wu, Guoyao

    2013-01-01

    Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4, or 8 ?g IFNT/kg body weight (BW) per day (n = 6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose, and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, as well as leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 ?g IFNT/kg BW/day in comparison with control rats. Treatment with 8 ?g IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared with control rats. Oral administration of 8 µg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver, and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals. PMID:23804503

  20. Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats

    PubMed Central

    Schiepers, Olga J. G.; Schoffelmeer, Anton N. M.; Cuppen, Edwin; Vanderschuren, Louk J. M. J.

    2007-01-01

    Rationale Serotonin is an important modulator of social behaviour. Individual differences in serotonergic signalling are considered to be a marker of personality that is stable throughout lifetime. While a large body of evidence indicates that central serotonin levels are inversely related to aggression and sexual behaviour in adult rats, the relationship between serotonin and social behaviour during peri-adolescence has hardly been explored. Objective To study the effect of acute and constitutive increases in serotonin neurotransmission on social behaviour in peri-adolescent rats. Materials and methods Social behaviour in peri-adolesent rats (28–35 days old) was studied after genetic ablation of the serotonin transporter, causing constitutively increased extra-neuronal serotonin levels, and after acute treatment with the serotonin reuptake inhibitor fluoxetine or the serotonin releasing agent 3,4-methylenedioxymethamphetamine (MDMA). A distinction was made between social play behaviour that mainly occurs during peri-adolescence, and non-playful social interactions that are abundant during the entire lifespan of rats. Results In serotonin transporter knockout rats, social play behaviour was markedly reduced, while non-playful aspects of social interaction were unaffected. Acute treatment with fluoxetine or MDMA dose-dependently inhibited social play behaviour. MDMA also suppressed non-playful social interaction but at higher doses than those required to reduce social play. Fluoxetine did not affect non-playful social interaction. Conclusions These data show that both acute and constitutive increases in serotonergic neurotransmission reduce social play behaviour in peri-adolescent rats. Together with our previous findings of reduced aggressive and sexual behaviour in adult serotonin transporter knockout rats, these data support the notion that serotonin modulates social behaviour in a trait-like manner. PMID:17661017

  1. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.

    PubMed Central

    Sharpe, R M; Fisher, J S; Millar, M M; Jobling, S; Sumpter, J P

    1995-01-01

    This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens. Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 3. C Figure 3. D Figure 4. PMID:8747020

  2. Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats.

    PubMed

    Mahfouz, M M; Kummerow, F A

    2005-05-01

    The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity. PMID:15967162

  3. Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats.

    PubMed

    Page, Gayle G; Opp, Mark R; Kozachik, Sharon L

    2014-08-01

    Studies in humans suggest that female sex, reduced sleep opportunities and biological stress responsivity increase risk for developing persistent pain conditions. To investigate the relative contribution of these three factors to persistent pain, we employed the Sciatic Inflammatory Neuritis (SIN) model of repeated left sciatic perineurial exposures to zymosan, an inflammatory stimulus, to determine their impact upon the development of persistent mechanical hypersensitivity. Following an initial moderate insult, a very low zymosan dose was infused daily for eight days to model a sub-threshold inflammatory perturbation to which only susceptible animals would manifest or maintain mechanical hypersensitivity. Using Sprague Dawley rats, maintaining wakefulness throughout the first one-half of the 12-h light phase resulted in a bilateral reduction in paw withdrawal thresholds (PWTs); zymosan infusion reduced ipsilateral PWTs in all animals and contralateral PWTs only in females. This sex difference was validated in Fischer 344, Lewis and Sprague Dawley rats, suggesting that females are the more susceptible phenotype for both local and centrally driven responses to repeated low-level inflammatory perturbations. Hypothalamic-pituitary-adrenal (HPA) axis hyporesponsive Lewis rats exhibited the most robust development of mechanical hypersensitivity and HPA axis hyperresponsive Fischer 344 rats matched the Lewis rats' mechanical hypersensitivity throughout the latter four days of the protocol. If HPA axis phenotype does indeed influence these findings, the more balanced responsivity of Sprague Dawley rats would seem to promote resilience in this paradigm. Taken together, these findings are consistent with what is known regarding persistent pain development in humans. PMID:24594386

  4. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    SciTech Connect

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle [University of British Columbia, Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC (Canada); Pospisilik, John Andrew [Institute of Molecular Biotechnology, Vienna (Austria); Lynn, Francis [HRI, Diabetes Center, University of California San Francisco, CA (United States); Manhart, Susanne; Demuth, Hans-Ulrich [Probiodrug AG, Biocenter, Halle (Saale) (Germany); Speck, Madeleine; Pederson, Raymond A. [University of British Columbia, Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC (Canada); McIntosh, Christopher H.S. [University of British Columbia, Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC (Canada)], E-mail: mcintoch@interchange.ubc.ca

    2007-11-03

    In type 2 diabetes (T2DM) {beta}-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 {+-} 3.8%) than ZF rats (48.8 {+-} 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 {+-} 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.

  5. Efficacy of hand-broadcast application of baits containing 0.005% diphacinone in reducing rat populations in Hawaiian forests

    USGS Publications Warehouse

    Foote, David; Lindsey, Gerald D.; Perry, Charlotte F.; Spurr, Eric

    2013-01-01

    Introduced black rats (Rattus rattus), Polynesian rats (R. exulans/i>), and Norway rats (R. norvegicus) impact insular bird, plant, and invertebrate populations worldwide. We investigated the efficacy of hand-broadcast application of Ramik® Green containing 0.005% diphacinone for rodent control in paired 4-ha treatment and non-treatment plots in both wet and mesic forest in Hawai?i. Radio telemetry of black rats, the predominant species, indicated 100% mortality in both treatment plots within about one week of bait application. Live trapping and non-toxic census bait block monitoring two to four weeks after each of 12 repeat bait applications in the wet forest, and three repeat bait applications in the mesic forest, indicated rat abundance was reduced on average by 84–88%. However, reinvasion could have occurred within this time. Rat populations in the treatment plots usually recovered to pre-poison levels within two to five months. House mice (Mus musculus), Indian mongooses (Herpestes auropunctatus), and feral cats (Felis catus) also ate bait or other animals that had eaten bait. This study demonstrates the efficacy of ground-based broadcast toxicant baits for the control of rats in Hawaiian montane wet forests.

  6. Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum

    PubMed Central

    Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2015-01-01

    Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC) is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium) in a murine model of DIA. The astrocyte density was significantly reduced (~34%) for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR) also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC.

  7. The cocarcinogenic effect of intrarectal deoxycholate in rats is reduced by oral metronidazole.

    PubMed Central

    Rainey, J. B.; Maeda, M.; Williams, C.; Williamson, R. C.

    1984-01-01

    Bile acids enhance colorectal carcinogenesis in animals and man, perhaps after degradation by faecal anaerobes. The promotional effect of sodium deoxycholate (SDC) and its relationship to bacteria was examined in male Sprague-Dawley rats (n = 115) which had received a 6-week course of azoxymethane (total dose 90 mg kg-1 s.c.) Two groups received 3 X weekly intrarectal (i.r.) instillations of N saline or 0.12 M SDC for 18 weeks. Another group received SDC i.r. plus metronidazole (22.5 mg kg-1) daily in the drinking water. Controls had no instillations or metronidazole alone. By 28 weeks SDC had increased mean colonic crypt depth by 9% (P less than 0.001), and had almost trebled colorectal tumour yields from 2.4 +/- 0.4 per rat (mean +/- s.e.) in controls to 6.4 +/- 0.5 (P less than 0.001). Tumour yields after SDC + metronidazole (4.2 +/- 0.5) remained 75% higher than in controls (P less than 0.01) but were 33% less than after SDC alone (P less than 0.01), and the increase in crypt depth was maintained at 7% (P less than 0.001). Neither metronidazole alone nor saline i.r. had any effect on tumour yield, but metronidazole alone reduced crypt depth by 9% (P less than 0.001). Deoxycholate is a potent cocarcinogen and also stimulates mucosal hyperplasia. Metronidazole reduces its tumour-promoting effect, suggesting that faecal anaerobes are important in bile acid cocarcinogenesis. PMID:6722011

  8. Ulinastatin reduces pathogenesis of phosgene-induced acute lung injury in rats.

    PubMed

    Shen, Jie; Gan, Zhengyi; Zhao, Jie; Zhang, Liming; Xu, Guoxiong

    2014-10-01

    Phosgene (CG) is an industrial chemical used to make plastics, rubbers, dyestuff, and pesticides. Although the inhalation of CG is relatively uncommon, its accidental exposure can lead to acute lung injury (ALI). Ulinastatin, a urinary trypsin inhibitor, has been emerged to use for the treatment of acute inflammatory state of a number of organs including the lung. In this study, we examined the pathogenic changes in the lungs after the inhalation of CG gas and also examined the effect of ulinastatin treatment in reversing these changes in rats. We found that the rats exposed to CG gas at a dose of 5.0 g/m(3) for 5 min led to ALI after 6 h. The signs of lung injury include pulmonary edema, hemorrhage, and cellular infiltration in pulmonary alveoli. In addition, interleukin-15 (IL-15) and intercellular adhesion molecule-1 (ICAM-1) were significantly increased in CG-inhaled animals. Ulinastatin administration at 1 h postexposure significantly reduced the intensity of all the pathological changes in the lungs of these CG-exposed animals. Ulinastatin at a dose of 400 U/g was shown to decrease the total number of cells in bronchoalveolar lavage fluid and the levels of IL-15 and ICAM-1 in the serum. We also found that the structure of the lung was protected by ulinastatin treatment. Thus, our data suggest that ulinastatin can be used as an effective drug for the treatment of CG-induced ALI. The serum levels of IL-15 and ICAM-1 can be used as the markers of lung injury after exposure to CG and may also serve as useful therapeutic targets at an early stage. The effects of long-term treatment of ulinastatin and the mechanisms by which ulinastatin decreases the infiltration of blood cells and reduces cytokines need further investigation. PMID:23075575

  9. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury.

    PubMed

    Lu, Dunyue; Goussev, Anton; Chen, Jieli; Pannu, Paul; Li, Yi; Mahmood, Asim; Chopp, Michael

    2004-01-01

    Statins administered postischemia promote functional improvement in rats, independent of their capability to lower cholesterol. We therefore tested the effect of statin treatment on traumatic brain injury (TBI) in rats. Atorvastatin was orally administered (1 mg/kg/day) to Wistar rats starting 1 day after TBI for 7 consecutive days. Control animals received saline. Modified Neurological Severity Scores and Corner tests were utilized to evaluate functional response to treatment. Bromodeoxyuridine (BrdU, 100 mg/kg) was also intraperitoneally injected daily for 14 consecutive days to label the newly generated endothelial cells. Rats were sacrificed at day 14 after TBI, and the brain samples were processed for immunohistochemical staining. Atorvastatin administration after brain injury significantly reduced the neurological functional deficits, increased neuronal survival and synaptogenesis in the boundary zone of the lesion and in the CA3 regions of the hippocampus, and induced angiogenesis in these regions. The results suggest that atorvastatin may provide beneficial effects in experimental TBI. PMID:14987462

  10. Fenugreek with reduced bitterness prevents diet-induced metabolic disorders in rats

    PubMed Central

    2012-01-01

    Background Various therapeutic effects of fenugreek (Trigonella foenum-graecum L.) on metabolic disorders have been reported. However, the bitterness of fenugreek makes it hard for humans to eat sufficient doses of it for achieving therapeutic effects. Fenugreek contains bitter saponins such as protodioscin. Fenugreek with reduced bitterness (FRB) is prepared by treating fenugreek with beta-glucosidase. This study has been undertaken to evaluate the effects of FRB on metabolic disorders in rats. Methods Forty Sprague–Dawley rats were fed with high-fat high-sucrose (HFS) diet for 12 week to induce mild glucose and lipid disorders. Afterwards, the rats were divided into 5 groups. In the experiment 1, each group (n?=?8) was fed with HFS, or HFS containing 2.4% fenugreek, or HFS containing 1.2%, 2.4% and 4.8% FRB, respectively, for 12 week. In the experiment 2, we examined the effects of lower doses of FRB (0.12%, 0.24% and 1.2%) under the same protocol (n?=?7 in each groups). Results In the experiment 1, FRB dose-dependently reduced food intake, body weight gain, epididymal white adipose tissue (EWAT) and soleus muscle weight. FRB also lowered plasma and hepatic lipid levels and increased fecal lipid levels, both dose-dependently. The Plasma total cholesterol levels (mmol/L) in the three FRB and Ctrl groups were 1.58?±?0.09, 1.45?±?0.05*, 1.29?±?0.07* and 2.00?±?0.18, respectively (*; P?

  11. Disinhibition reduces extracellular glutamine and elevates extracellular glutamate in rat hippocampus in vivo.

    PubMed

    Kanamori, Keiko

    2015-08-01

    Disinhibition was induced in the hippocampal CA1/CA3 region of normal adult rats by unilateral perfusion of the GABAAR antagonist, 4-[6-imino-3-(4-methoxyphenyl)pyridazin-1-yl] butanoic acid hydrobromide (gabazine), or a GABABR antagonist, p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid (CGP 35348), through a microdialysis probe. Effects of disinhibition on EEG recordings and the concentrations of extracellular glutamate (GLUECF), the major excitatory neurotransmitter, and of extracellular glutamine (GLNECF), its precursor, were examined bilaterally in freely behaving rats. Unilateral perfusion of 10?M gabazine in artificial CSF of normal electrolyte composition for 34min induced epileptiform discharges which represent synchronized glutamatergic population bursts, not only in the gabazine-perfused ipsilateral hippocampus, but also in the aCSF-perfused contralateral hippocampus. The concentration of GLUECF remained unchanged, but the concentration of its precursor, GLNECF, decreased to 73±4% (n=5) of the baseline during frequent epileptiform discharges, not only in the ipsilateral, but also in the contralateral hippocampus, where the change can be attributed to recurrent epileptiform discharges per se, with recovery to 95% of baseline when epileptiform discharges diminished. The blockade of GABABR, by CGP 35348 perfusion in the ipsilateral hippocampus for 30min, induced bilateral Na(+) spikes in extracellular recording. These can reasonably be attributed to somatic and dendritic action potentials and are indicative of synchronized excitatory activity. This disinhibition induced, in both hippocampi, (a) transient 1.6-2.4-fold elevation of GLUECF which correlated with the number of Na(+) spike cluster events and (b) concomitant reduction of GLNECF to ?70%. Intracellular GLN concentration was measured in the hippocampal CA1/CA3 region sampled by microdialysis in separate groups of rats by snap-freezing the brain after 25min of gabazine perfusion or 20min of CGP perfusion when extracellular GLN (GLNECF) was 60-70% of the pre-perfusion level. These intracellular GLN concentrations in the disinhibited hippocampi showed no statistically significant difference from the untreated control. This result strongly suggests that the observed decrease of GLNECF is not due to reduced glutamine synthesis or decrease in the rate of efflux of GLN to ECF. This strengthens the likelihood that reduced GLNECF reflects increased GLN uptake into neurons to sustain enhanced GLU flux during excitatory population bursts in disinhibited hippocampus. The results are consistent with the emerging concept that neuronal uptake of GLNECF plays a major role in sustaining epileptiform activities in the kainate-induced model of temporal-lobe epilepsy. PMID:26088883

  12. Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

    PubMed

    Baracz, Sarah J; Everett, Nicholas A; McGregor, Iain S; Cornish, Jennifer L

    2014-11-16

    The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1?mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5?pmol, 1.5?pmol, 4.5?pmol) or co-administration of oxytocin (1.5?pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1?nmol, 3?nmol) in the NAc core (500?nl/side) was examined on METH-primed (1?mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking. PMID:25399704

  13. Reduced effect of caffeine on twitch contraction of oesophageal striated muscle from stroke-prone spontaneously hypertensive rats.

    PubMed

    Sekiguchi, Fumiko; Kawata, Kyoko; Shimamura, Keiichi; Sunano, Satoru

    2003-04-01

    1. There are known differences in the sensitivity to caffeine between skeletal muscle (soleus) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The present study was performed in order to examine differences in the effects of caffeine on twitch contraction between visceral striated muscle using the outer layer of the oesophagus from WKY rats and stroke-prone SHR (SHRSP). 2. Caffeine, at concentrations ranging from 0.3 to 10 mmol/L, exhibited potentiating effects on twitch contraction in preparations from both WKY rats and SHRSP. The potentiating effect of caffeine was markedly less prominent in preparations from SHRSP compared with preparations from WKY rats. 3. The rate of contraction and relaxation, the time to peak tension and 80% relaxation time were not significantly altered by caffeine at concentrations lower than 3 mmol/L in preparations from either strain. 4. With 10 mmol/L caffeine, the rate of relaxation was markedly reduced and the 80% relaxation time was prolonged, with no significant changes in the rate of contraction, in preparations from WKY rats. These changes were significantly smaller in preparations from SHRSP. 5. The duration of the action potential was greater in preparations from SHRSP than in preparations from WKY rats, although the membrane potential and the amplitude of the action potential were not significantly different between preparations from WKY rats and SHRSP. 6. Caffeine, at 10 mmol/L, prolonged the duration of the action potential in preparations from both strains. The effect of caffeine was not different between preparations from WKY rats and SHRSP. 7. The results of the present study suggest that caffeine augments release of Ca2+ from the sarcoplasmic reticulum (SR) at low concentrations and attenuates Ca2+ re-uptake at 10 mmol/L. Decreased reactivity of SR to caffeine may be a cause of the lesser potentiation of twitch contraction by caffeine in preparations from SHRSP. PMID:12680839

  14. Yacon diet (Smallanthus sonchifolius, Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

    PubMed Central

    Satoh, H; Audrey Nguyen, M T; Kudoh, A; Watanabe, T

    2013-01-01

    Objective: Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose. Methods: We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study. Results: Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7?mg?dl?1 (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2?mg?kg?1 per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats. Conclusion: These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state. PMID:23712282

  15. Polyethylene glycol reduces inflammation and aberrant crypt foci in carcinogen-initiated rats

    Microsoft Academic Search

    Pernilla C. Karlsson; Roisin Hughes; Joseph J. Rafter; W. Robert Bruce

    2005-01-01

    Polyethylene glycol 8000 inhibits the formation of tumors and of aberrant crypt foci (ACF) in carcinogen-initiated rats. We asked: is the inhibition associated with a reduction of colonic inflammation and an increase in colonic cell permeability? Twenty-eight, male F 344 rats were divided into two groups, 10 control animals and 18 animals initiated with azoxymethane. Nine of the rats in

  16. [Exogenous hydrogen sulfide reduces vascular aging in D-galactose-induced subacute aging rats].

    PubMed

    Qiao, Wei-Li; Yang, Wen-Xue; Liu, Lei; Shi, Yue; Cui, Jie; Liu, Hong; Yan, Chang-Dong

    2014-06-25

    The present study was aimed to observe the protective effect of exogenous hydrogen sulfide (H?S) on vascular structural and functional changes of aorta in D-galactose-induced subacute aging rats. Adult male SD rats were randomly divided to five groups: the vehicle group, the D-galactose (D-gal) group, and the three NaHS groups treated with low (1 ?mol·kg?ą·d?ą), middle (10 ?mol·kg?ą·d?ą) or high (100 ?mol·kg?ą·d?ą) dose of NaHS respectively. The D-gal group rats were given subcutaneously injection of 125 mg/kg D-gal per day for eight weeks to induce subacute aging model. In the NaHS group, D-gal was administered as above but with NaHS intraperitoneally injected at a dosage of 1, 10, 100 ?mol·kg?ą·d?ą respectively. Equivalent volumes of saline were administered per day for eight weeks in vehicle group. Morphological changes of aorta were observed by HE and Masson staining. The level of H?S in serum, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), as well as anti-superoxide anions in vascular tissue were determined by spectrophotometry. Angiotensin II (AngII) levels in plasma were measured using competitive enzyme immunoassay. The expression of angiotensin II type 1 receptor (AT1R) in aorta was determined by Western blot. The results showed that the aging aortic morphologic changes in model rats were ameliorated in NaHS groups. Decreased vascular endothelial exfoliative cells and vascular smooth muscle cell (SMC) proliferation were shown in NaHS groups by HE staining. Masson staining analysis showed reduced relative contents of collagen fibers (P < 0.05) and SMC (P < 0.05) in NaHS groups. Compared to vehicle group, serum concentration of H?S in D-gal group was decreased, while it was increased in NaHS groups after treatment with NaHS (P < 0.05). In the D-gal group, the concentration of AngII in plasma was significantly increased compared with that in vehicle group, while it was decreased in NaHS groups (P < 0.05). Moreover, levels of vascular tissue anti-superoxide anion and the activity of SOD were obviously higher, MDA was significantly lower in all NaHS treated groups than those in the D-gal group respectively (P < 0.05). Western blot analysis showed that the expression of AT1R was increased in D-gal group compared with that in vehicle group, while it was decreased after treatment with NaHS compared with that in D-gal group (P < 0.05). These results suggest that exogenous H?S can ameliorate the age-related changes of aortic morphology, decrease the concentration of AngII in plasma, down-regulate the expression of AT1R in vascular tissue, and mitigate the level of oxidative stress. These changes delay the vascular aging in aging rats ultimately. PMID:24964843

  17. The mineralocorticoid receptor antagonist eplerenone reduces renal interstitial fibrosis after long-term cyclosporine treatment in rat: antagonizing cyclosporine nephrotoxicity

    PubMed Central

    2013-01-01

    Background Chronic cyclosporine-(CsA)-mediated loss of kidney function is a major clinical problem in organ transplantation. We hypothesized that the mineralocorticoid receptor antagonist eplerenone (EPL) prevents chronic CsA-induced renal interstitial volume increase, tubule loss, and functional impairment in a rat model. Methods Sprague–Dawley rats received CsA alone (15 mg/kg/d p.o.), CsA and EPL (approximately 100 mg/kg/day p.o.) or vehicle (control) for 12 weeks. At 11 weeks, chronic indwelling arterial and venous catheters were implanted for continuous measurements of arterial blood pressure (BP) and GFR (inulin clearance) in conscious, freely moving animals. Plasma was sampled for analysis and kidney tissue was fixed for quantitative stereological analyses. Results Compared to controls, CsA-treatment reduced relative tubular volume (0.73±0.03 vs. 0.85±0.01, p<0.05) and increased relative interstitial volume (0.080±0.004 vs. 0.045±0.003, p<0.05); EPL attenuated these changes (0.82±0.02, p<0.05, and 0.060±0.006, p<0.05, respectively). CsA-treated rats had more sclerotic glomeruli and a higher degree of vascular depositions in arterioles; both were significantly reduced in CsA+EPL-treated animals. CsA increased BP and reduced body weight gain and GFR. In CsA+EPL rats, weight gain, GFR and BP at rest (daytime) were normalized; however, BP during activity (night) remained elevated. Plasma sodium and potassium concentrations, kidney-to-body weight ratios and CsA whole blood concentration were similar in CsA and CsA+EPL rats. Conclusions It is concluded that in the chronic cyclosporine rat nephropathy model, EPL reduces renal tissue injury, hypofiltration, hypertension, and growth impairment. MR antagonists should be tested for their renoprotective potential in patients treated with calcineurin inhibitors. PMID:23425330

  18. Hypothyroidism reduces tricarboxylate carrier activity and expression in rat liver mitochondria by reducing nuclear transcription rate and splicing efficiency.

    PubMed

    Siculella, Luisa; Sabetta, Simona; Giudetti, Anna M; Gnoni, Gabriele V

    2006-07-14

    The tricarboxylate carrier (TCC), also known as citrate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. The effect of hypothyroidism on the activity and expression of the hepatic mitochondrial TCC was investigated in this study. TCC activity was significantly decreased in hypothyroid rats as compared with euthyroid animals. This hormone deficiency effect was due to a reduction in the amount of carrier protein, which resulted from a proportionate decrease of the specific mRNA. Hypothyroidism did not influence TCC mRNA stability. On the other hand, nuclear run-on assay revealed that the transcriptional rate of TCC mRNA decreased by approximately 40% in the nuclei from hypothyroid versus euthyroid rats. In addition, the ribonuclease protection assay showed that, in the nuclei of hypothyroid rats, the ratio of mature to precursor RNA decreased, indicating that the splicing of TCC RNA is affected. Furthermore, we found that the ratio of polyadenylated/unpolyadenylated TCC RNA as well as the length of the TCC RNA poly(A) tail were similar in both euthyroid and hypothyroid rats. Thus, the rate of formation of the TCC 3'-end is not altered in hypothyroidism. These results suggest that hypothyroidism affects TCC expression at both the transcriptional and post-transcriptional levels. PMID:16682415

  19. Honokiol protects rat hearts against myocardial ischemia reperfusion injury by reducing oxidative stress and inflammation

    PubMed Central

    WANG, YUN; ZHANG, ZHONG-ZE; WU, YUN; ZHAN, JIA; HE, XIANG-HU; WANG, YAN-LIN

    2013-01-01

    Honokiol, a potent radical scavenger, has been demonstrated to ameliorate cerebral infarction following ischemia/reperfusion (I/R) injury. However, its effects on myocardial I/R injury remain unclear. The present study aimed to examine the effects of honokiol on myocardial I/R injury and to investigate its potential cardioprotective mechanisms. Sprague-Dawley rats were pretreated with honokiol and exposed to a 30-min myocardial ischemia followed by 2-h coronary reperfusion. Myocardial I/R-induced infarct size and biochemical and histological changes were compared. The expression of nuclear factor ?B(NF-?B; p65) was assessed by western blotting. Pretreatment with honokiol significantly reduced infarct size, and serum creatine kinase (CK) and lactate dehydrogenase (LDH) release compared with those in the I/R group following a 2-h reperfusion. The malondialdehyde (MDA) level, myeloperoxidase (MPO) activity, concentrations of tumor necrosis factor (TNF)-? and interleukin (IL)-6 and expression level of NF-?B were all reduced by honokiol pretreatment, while honokiol inhibited the decreases in superoxide dismutase (SOD) and catalase (CAT) activities. In addition, less neutrophil infiltration and histopathological damage in the myocardium were observed in the honokiol-pretreated group. These findings indicate that honokiol pretreatment diminished myocardial I/R injury through attenuation of oxidative stress and inflammation. PMID:23251290

  20. PHTHALATE ESTER-INDUCED GUBERNACULAR LESIONS ARE ASSOCIATED WITH REDUCED INSL-3 GENE EXPRESSION IN THE FETAL RAT TESTIS

    EPA Science Inventory

    Phthalate ester-induced gubernacular ligament lesions are associated with reduced Insl3 gene expression in the fetal rat testis during sexual differentiation. VS Wilson, C Lambright, J Furr, J Ostby, C Wood, G Held, LE Gray Jr. U.S. EPA, ORD, NHEERL, Reproductive Toxicology...

  1. Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided

    Microsoft Academic Search

    Scott E Krahl; Shayani S Senanayake; Adrian Handforth

    2003-01-01

    As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left

  2. Spontaneously reduced body temperature and gasping ability as a mechanism of extreme tolerance to asphyxia in neonatal rats

    Microsoft Academic Search

    Justyna Rogalska; Micha? Caputa

    2005-01-01

    The aim of the investigation was to verify our hypothesis that extreme tolerance of newborn rodents to anoxia is determined by their ability to maintain reduced body temperature and to keep on gasping.Newborn Wistar rats were used. In separate experiments we checked (1) effect of extreme thermal conditions on rectal temperature (Tre) of the newborns in their nests; (2) effect

  3. Water Extracts of Helicobacter pylori Suppress the Expression of Histidine Decarboxylase and Reduce Histamine Content in the Rat Gastric Mucosa

    Microsoft Academic Search

    Peter C. Konturek; Tomasz Brzozowski; Aleksandra Duda; Eckhart G. Hahn

    2000-01-01

    Background: Acute Helicobacter pylori (Hp) infection in humans may be associated with markedly reduced gastric acid secretion, but the mechanism of this hypochlorhydria has not been fully explained. Aims: This study was designed to investigate how water extracts (WE) of Hp applied on rat gastric mucosa affect gastric secretion and mucosal histamine concentration as well as the gene expression for

  4. Nigella sativa oil reduces aluminium chloride-induced oxidative injury in liver and erythrocytes of rats.

    PubMed

    Bouasla, Ihcene; Bouasla, Asma; Boumendjel, Amel; Messarah, Mahfoud; Abdennour, Cherif; Boulakoud, Mohamed Salah; El Feki, Abdelfattah

    2014-12-01

    The present study was planned to investigate the protective effects of Nigella sativa oil (NSO) supplementation against aluminium chloride (AlCl3)-induced oxidative damage in liver and erythrocytes of rats. Simultaneously, a preliminary phytochemical study was affected in order to characterize the bioactive components containing in the NSO using chemical assays. The antioxidant capacities of NSO were evaluated by DPPH assay. The results showed that NSO was found to contain large amounts of total phenolics, flavonoids and tannins. Twenty-four rats were equally divided into two groups, in which group A received standard diet, whereas group B treated daily with an oral gavage dose of 2 ml NSO/kg body weight. After 5 weeks pretreatment, both groups were divided again into two subgroups (A and B) of six animals each and treated for other 3 weeks. Therefore, subgroup A1 was served as a control which received standard diet, but subgroup A2 received AlCl3 (34 mg/kg bw mixed with food). Subgroup B1 received both AlCl3 and NSO; however, subgroup B2 received NSO only. Results showed that AlCl3 exhibited an increase in white blood cell counts and a marked decrease in erythrocyte counts and haemoglobin content. Plasma aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase activities and total bilirubin concentration were higher in AlCl3 group than those of the control, while albumin and total protein concentration were significantly lower. Compared to the control, a significant raise of hepatic and erythrocyte malondialdehyde level associated with a decrease in reduced glutathione content, glutathione peroxidase, superoxide dismutase and catalase, activities of AlCl3 treated rats. However, the administration of NSO alone or combined with AlCl3 has improved the status of all parameters studied. It can be concluded that AlCl3 has induced the oxidative stress, altered the biochemical parameters and the hepatic histological profile, but the supplementation of NSO has alleviated such toxicity. PMID:25164035

  5. Relaxation of Rat Aorta by Farrerol Correlates with Potency to Reduce Intracellular Calcium of VSMCs

    PubMed Central

    Qin, Xiaojiang; Hou, Xiaomin; Zhang, Mingsheng; Liang, Taigang; Zhi, Jianmin; Han, Lingge; Li, Qingshan

    2014-01-01

    Farrerol, isolated from Rhododendron dauricum L., has been proven to be an important multifunctional physiologically active component, but its vasoactive mechanism is not clear. The present study was performed to observe the vasoactive effects of farrerol on rat aorta and to investigate the possible underlying mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and the myogenic effects stimulated by farrerol were studied. Intracellular Ca2+ ([Ca2+]in) was measured by molecular probe fluo-4-AM and the activities of L-type voltage-gated Ca2+ channels (LVGC) were studied with whole-cell patch clamp in cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol significantly induced dose-dependent relaxation on aortic rings, while this vasorelaxation was not affected by NG-nitro-l-arginine methylester ester or endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca2+-induced contraction on the basis of the stable contraction induced by KCl or phenylephrine (PE) in Ca2+-free solution. Moreover, after incubation with verapamil, farrerol can induce relaxation in endothelium-denuded aortas precontracted by PE, and this effect can be enhanced by ruthenium red, but not by heparin. With laser scanning confocal microscopy method, the farrerol-induced decline of [Ca2+]in in cultured VSMCs was observed. Furthermore, we found that farrerol could suppress Ca2+ influx via LVGC by patch clamp technology. These findings suggested that farrerol can regulate the vascular tension and could be developed as a practicable vasorelaxation drug. PMID:24747597

  6. Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats.

    PubMed

    Gonzaga, Natalia A; Mecawi, André S; Antunes-Rodrigues, José; De Martinis, Bruno S; Padovan, Claudia M; Tirapelli, Carlos R

    2015-02-01

    We analyzed the effects of ethanol withdrawal on the vascular and systemic renin-angiotensin system (RAS) and vascular oxidative stress. Male Wistar rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the elevated-plus maze (EPM) and increased plasma corticosterone levels. Ethanol withdrawal significantly increased systolic blood pressure and plasma angiotensin II (ANG II) levels without an effect on plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, or plasma angiotensin I (ANG I) levels. No differences in vascular ANG I, ANG II levels, and ACE activity/expression and AT1 and AT2 receptor expression were detected among the experimental groups. Plasma osmolality, as well as plasma sodium, potassium, and glucose levels were not affected by ethanol withdrawal. Ethanol withdrawal induced systemic and vascular oxidative stress, as evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels and the vascular generation of superoxide anion. Ethanol withdrawal significantly decreased plasma and vascular nitrate/nitrite levels. Major new findings of the present study are that ethanol withdrawal induces vascular oxidative stress and reduces nitric oxide (NO) levels in the vasculature. Additionally, our study provides novel evidence that ethanol withdrawal does not affect the vascular ANG II generating system while stimulating systemic RAS. These responses could predispose individuals to the development of cardiovascular diseases. PMID:25557835

  7. Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta.

    PubMed

    Sekiguchi, Fumiko; Yanamoto, Aiko; Sunano, Satoru

    2004-04-01

    The involvement of the superoxide anion in endothelium-dependent relaxation (EDR) was examined in noradrenaline-contracted aortic smooth muscle preparations isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acetylcholine (ACh, 10(-9)-10(-5) M) induced EDR in both WKY and SHRSP preparations in a concentration-dependent manner, but with a significantly smaller amplitude in those from SHRSP than in those from WKY. The ACh-induced EDR was inhibited by N(omega)-nitro-L-arginine (L-NOARG), in a concentration-dependent manner, both in WKY and SHRSP. The EDR produced in WKY in the presence of 3 x 10(-6) M L-NOARG was similar in magnitude to that produced in SHRSP in the absence of L-NOARG. Superoxide dismutase (SOD, 300 units/ml) increased the amplitude of EDR in SHRSP but not in WKY, with no alteration of the threshold or of the maximal amplitude. The maximal amplitude of EDR produced in SHRSP in the presence of SOD was still smaller than that in WKY. In WKY, a possible involvement of superoxide in the EDR was examined in aortae whose EDR was partially inhibited by treatment with a subthreshold concentration (3 x 10 (-6) M) of L-NOARG. In the L-NOARG-conditioned aorta, the reduced EDR was partially but significantly recovered by SOD. These results suggest that the impaired EDR in aortae of SHRSP may be causally related to a higher production of superoxide. The L-NOARG-induced inhibition of EDR in WKY may be produced, in part, by the reduction of effective NO due to its destruction by superoxide. PMID:15215634

  8. Adult hippocampal neurogenesis is reduced by sleep fragmentation in the adult rat

    PubMed Central

    Guzman-Marin, Ruben; Bashir, Tariq; Suntsova, Natalia; Szymusiak, Ronald; McGinty, Dennis

    2007-01-01

    The adult hippocampal dentate gyrus (DG) is a site of continuing neurogenesis. This process is influenced by a variety of physiological and experiential stimuli including total sleep deprivation (TSD). In humans, sleep fragmentation (SF) is a more common sleep condition than TSD. SF is associated with several prevalent diseases. We assessed a hypothesis that SF would suppress adult neurogenesis in the DG of the adult rat. An intermittent treadmill system was used; the treadmill was on for 3 s and off for 30 s (SF). For sleep fragmentation control (SFC), the treadmill was on for 15 min and off for 150 min. SF was conducted for 3 durations: 1, 4 and 7 days. To label proliferating cells, the thymidine analog, BrdU, was injected two hours prior to the end of each experiment. Expression of the intrinsic proliferative marker, Ki67, was also studied. SF rats exhibited an increased number of NREM sleep bouts with no change in the percent of time spent during this stage. The numbers of both BrdU-positive cells and Ki67-positive cells were reduced by ~ 70 % (P < 0.05) in the SF groups after 4 and 7 days of experimental conditions whereas no differences were observed after 1 day. In a second experiment, we found that the percentage of new cells expressing a neuronal phenotype three weeks after BrdU administration was lower in the SF in comparison with the SFC group for all 3 durations of SF. We also examined the effects of SF on proliferation in adrenalectomized (ADX) animals, with basal corticosterone replacement. ADX SF animals exhibited a 55% reduction in the number of BrdU-positive cells when compared with ADX SFC. Thus, elevated glucocorticoids do not account for most of the reduction in cell proliferation induced by the SF procedure, although a small contribution of stress is not excluded. The results show that sustained SF induced marked reduction in hippocampal neurogenesis. PMID:17630219

  9. ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats.

    PubMed

    Farraj, Aimen K; Hazari, Mehdi S; Haykal-Coates, Najwa; Lamb, Christina; Winsett, Darrell W; Ge, Yue; Ledbetter, Allen D; Carll, Alex P; Bruno, Maribel; Ghio, Andy; Costa, Daniel L

    2011-02-01

    Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an important contributor to ambient fine particulate air pollution. We hypothesized that a single-inhalation exposure to transition metal-rich PM will cause concentration-dependent cardiovascular toxicity in spontaneously hypertensive (SH) rats. Rats implanted with telemeters to monitor heart rate and electrocardiogram were exposed once by nose-only inhalation for 4 hours to 3.5 mg/m(3), 1.0 mg/m(3), or 0.45 mg/m(3) of a synthetic PM (dried salt solution), similar in composition to a well-studied ROFA sample consisting of Fe, Ni, and V. Exposure to the highest concentration of PM decreased T-wave amplitude and area, caused ST depression, reduced heart rate (HR), and increased nonconducted P-wave arrhythmias. These changes were accompanied by increased pulmonary inflammation, lung resistance, and vagal tone, as indicated by changes in markers of HR variability (increased root of the mean of squared differences of adjacent RR intervals [RMSSD], low frequency [LF], high frequency [HF], and decreased LF/HF), and attenuated myocardial micro-RNA (RNA segments that suppress translation by targeting messenger RNA) expression. The low and intermediate concentrations of PM had less effect on the inflammatory, HR variability, and micro-RNA endpoints, but still caused significant reductions in HR. In addition, the intermediate concentration caused ST depression and increased QRS area, whereas the low concentration increased the T-wave parameters. Thus, PM-induced cardiac dysfunction is mediated by multiple mechanisms that may be dependent on PM concentration and myocardial vulnerability (this abstract does not reflect the policy of the United States Environmental Protection Agency). PMID:20378750

  10. Reduced Endothelium-Dependent Relaxation to Anandamide in Mesenteric Arteries from Young Obese Zucker Rats

    PubMed Central

    Lobato, Nubia S.; Filgueira, Fernando P.; Prakash, Roshini; Giachini, Fernanda R.; Ergul, Adviye; Carvalho, Maria Helena C.; Webb, R. Clinton; Tostes, Rita C.; Fortes, Zuleica B.

    2013-01-01

    Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity. PMID:23667622

  11. Is the left forelimb preference indicative of a stressful situation in horses?

    PubMed

    Siniscalchi, M; Padalino, B; Lusito, R; Quaranta, A

    2014-09-01

    Evidence for behavioural and brain lateralisation is now widespread among the animal kingdom; lateralisation of limb use (pawedness) occurs in several mammals including both feral and domestic horses. We investigated limb preferences in 14 Quarter Horse during different motor tasks (walking, stepping on and off a step, truck loading and unloading). Population lateralisation was observed in two tasks: horses preferentially used their left forelimb during truck loading and stepping off a step. The results also revealed that horses showed higher scores for anxious behaviours during truck loading suggesting that the use of the left forelimb in this task may reflect the main role of the right hemisphere in control of behaviour during stressful situation. PMID:25108052

  12. Angiotensin Converting Enzyme Inhibition Reduces Cardiovascular Responses to Acute Stress in Myocardially Infarcted and Chronically Stressed Rats

    PubMed Central

    Cudnoch-Jedrzejewska, A.; Czarzasta, K.; Puchalska, L.; Dobruch, J.; Borowik, O.; Pachucki, J.; Szczepanska-Sadowska, E.

    2014-01-01

    Previous studies showed that chronically stressed and myocardially infarcted rats respond with exaggerated cardiovascular responses to acute stress. The present experiments were designed to elucidate whether this effect can be abolished by treatment with the angiotensin converting enzyme (ACE) inhibitor captopril. Sprague Dawley rats were subjected either to sham surgery (Groups 1 and 2) or to myocardial infarction (Groups 3 and 4). The rats of Groups 2 and 4 were also exposed to mild chronic stressing. Four weeks after the operation, mean arterial blood pressure (MABP) and heart rate (HR) were measured under resting conditions and after application of acute stress. The cardiovascular responses to the acute stress were determined again 24?h after administration of captopril orally. Captopril significantly reduced resting MABP in each group. Before administration of captopril, the maximum increases in MABP evoked by the acute stressor in all (infarcted and sham-operated) chronically stressed rats and also in the infarcted nonchronically stressed rats were significantly greater than in the sham-operated rats not exposed to chronic stressing. These differences were abolished by captopril. The results suggest that ACE may improve tolerance of acute stress in heart failure and during chronic stressing. PMID:25045668

  13. Candidate premotor neurones of skin reflex pathways to T1 forelimb motoneurones of the cat

    Microsoft Academic Search

    S. Kitazawa; Y. Ohki; M. Sasaki; M. Xi; T. Hongo

    1993-01-01

    This study explored the locations and input output properties of a large population of putative premotor neurones of skin reflex pathways in the cat. These neurones, interneurones excited by forelimb skin afferents and antidromically from the T1 motor nucleus (MN) and\\/or the lateral funiculus (LF, C8\\/T1 border), termed antidromic cells, were extracellularly recorded at C6-8. Selection of this site was

  14. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

    NASA Astrophysics Data System (ADS)

    Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

    2013-06-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

  15. Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.

    PubMed

    Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2012-05-01

    Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 ?g/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (<20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). PMID:21840572

  16. Reduced Ventricular Arrhythmogeneity and Increased Electrical Complexity in Normal Exercised Rats

    PubMed Central

    Dor-Haim, Horesh; Berenfeld, Omer; Horowitz, Michal; Lotan, Chaim; Swissa, Moshe

    2013-01-01

    Background The mechanisms whereby aerobic training reduces the occurrence of sudden cardiac death in humans are not clear. We test the hypothesis that exercise-induced increased resistance to ventricular tachycardia and fibrillation (VT/VF) involve an intrinsic remodeling in healthy hearts. Methods and Results Thirty rats were divided into a sedentary (CTRL, n?=?16) and two exercise groups: short- (4 weeks, ST, n?=?7) and long-term (8 weeks, LT, n?=?7) trained groups. Following the exercise program hearts were isolated and studied in a Langendorff perfusion system. An S1–S2 pacing protocol was applied at the right ventricle to determine inducibility of VT/VF. Fast Fourier transforms were applied on ECG time-series. In-vivo measurements showed training-induced increase in aerobic capacity, heart-to-body weight ratio and a 50% low-to-high frequency ratio reduction in the heart rate variability (p<0.05). In isolated hearts the probability for VF decreased from 26.1±14.4 in CTRL to 13.9±14.1 and 6.7±8.5% in the ST and LT, respectively (p<0.05). Duration of VF also decreased from 19.0±5.7 in CTRL to 8.8±7.1 and 6.0±5.8 sec in ST and LT respectively (p<0.05). Moreover, the pacing current required for VF induction increased following exercise (2.9±1.7 vs. 5.4±2.1 and 8.5±0.9 mA, respectively; p<0.05). Frequency analysis of ECG revealed an exercise-induced VF transition from a narrow single peak spectrum at 17 Hz in CTRL to a broader range of peaks ranging between 8.8 and 22.5 Hz in the LT group (p<0.05). Conclusion Exercise in rats leads to reduced VF propensity associated with an intrinsic cardiac remodeling related to a broader spectral range and faster frequency components in the ECG. PMID:23825553

  17. Reduced sympathetic neurite outgrowth on uterine tissue sections from rats treated with estrogen

    Microsoft Academic Search

    Analía Richeri; Paola Bianchimano; Keith A. Crutcher; M. Mónica Brauer

    2010-01-01

    In order to evaluate the contribution of substrate-bound factors to the extent and patterning of the sympathetic innervation\\u000a of rat uterus following estrogen treatment, superior cervical ganglion explants from neonatal and adult ovariectomized rats\\u000a were cultured on tissue sections of fresh frozen uterus from adult ovariectomized rats treated with estrogen or a vehicle.\\u000a The main findings were: (1) neurite growth

  18. Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

    PubMed Central

    2012-01-01

    Background Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Methods Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. Results MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Conclusions Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat. PMID:22545735

  19. Lycium barbarum polysaccharides reduce intestinal ischemia/reperfusion injuries in rats.

    PubMed

    Yang, Xuekang; Bai, Hua; Cai, Weixia; Li, Jun; Zhou, Qin; Wang, Yunchuan; Han, Juntao; Zhu, Xiongxiang; Dong, Maolong; Hu, Dahai

    2013-08-25

    Inflammation and oxidative stress exert important roles in intestinal ischemia-reperfusion injury (IRI). Lycium barbarum polysaccharides (LBPs) have shown effective antioxidative and immunomodulatory functions in different models. The purpose of the present study was to assess the effects and potential mechanisms of LBPs in intestinal IRI. Several free radical-generating and lipid peroxidation models were used to assess the antioxidant activities of LBPs in vitro. A common IRI model was used to induce intestinal injury by clamping and unclamping the superior mesenteric artery in rats. Changes in the malondialdehyde (MDA), tumor necrosis factor (TNF)-?, activated nuclear factor (NF)-?B, intracellular adhesion molecule (ICAM)-1, E-selectin, and related antioxidant enzyme levels, polymorphonuclear neutrophil (PMN) accumulation, intestinal permeability, and intestinal histology were examined. We found that LBPs exhibited marked inhibitory action against free radicals and lipid peroxidation in vitro. LBPs increased the levels of antioxidant enzymes and reduced intestinal oxidative injury in animal models of intestinal IRI. In addition, LBPs inhibited PMN accumulation and ICAM-1 expression and ameliorated changes in the TNF-? level, NF-?B activation, intestinal permeability, and histology. Our results indicate that LBPs treatment may protect against IRI-induced intestinal damage, possibly by inhibiting IRI-induced oxidative stress and inflammation. PMID:23743330

  20. Embelin Reduces Systemic Inflammation and Ameliorates Organ Injuries in Septic Rats Through Downregulating STAT3 and NF-?B Pathways.

    PubMed

    Zhou, Xian-Long; Huang, Lei; Cao, Jun

    2015-08-01

    Current evidence shows that the majority of the damage induced during sepsis is pursuant to induction and overproduction of endogenous cytokines. Embelin has been reported to suppress cytokine expressions in inflammatory disorders. The present study was designed to investigate the effects of embelin on cecal and ligation and puncture (CLP)-induced rat sepsis. Single-dose administration of embelin 1 h after surgery significantly improved survival of rats with CLP-induced sepsis. In addition, embelin treatment reduced the serum levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-?, interleukin (IL)-1?, and IL-6 and decreased organ inflammation and injuries. Moreover, embelin suppressed the activation of p65 subunit of nuclear factor-kappa B (NF-?B) and signal transducers and activators of transcription 3 (STAT3). Collectively, these results indicated that embelin ameliorates sepsis in rats through suppressing STAT3 and NF-?B pathways. PMID:25682469

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

    PubMed

    Zarubina, I V; Shabanov, P D

    2009-03-01

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

  2. Olanzapine reduced brown adipose tissue thermogenesis and locomotor activity in female rats.

    PubMed

    Zhang, Qingsheng; Lian, Jiamei; He, Meng; Deng, Chao; Wang, Hongqin; Huang, Xu-Feng

    2014-06-01

    Excessive weight gain has been identified as a serious metabolic side-effect of second-generation antipsychotics (SGAs), including olanzapine. While hyperphagia has been suggested to be the main contributor for this side-effect in the short term, reduced energy expenditure, in particular thermogenesis and locomotor activity, has been considered to contribute to the maintenance of heavy weight under long-term SGA treatments. Recent studies have identified metabolically active brown adipose tissues (BAT) in adult humans, suggesting potential clinical significance for the involvement of BAT thermogenesis in SGA-induced weight gain. However, to date there has been little research elucidating the central neuronal pathways affecting BAT thermogenesis or the morphological changes of the BAT. The present study aimed to investigate the role of BAT thermogenesis and locomotor activity in olanzapine-induced weight gain during the prolonged time courses of olanzapine treatment in an established female rat model. Although short- to mid-term olanzapine treatment had no effect on BAT temperature, we observed that long-term olanzapine treatment (from day 18 to 34) induced a significant reduction in BAT temperature, with an acute effect being observed between 45 and 150 min post-treatment in the long-term cohort. Additionally, in the long-term olanzapine group, the reduced BAT temperature was accompanied by decreased UCP1 and PGC-1? expressions in the BAT. Moreover, TH mRNA expressions in both hypothalamus and brainstem were also downregulated after mid- to long-term olanzapine treatment. Further, olanzapine led to reduced percentage of brown adipocytes in BAT during mid- to long-term treatments. Finally, locomotor activity was reduced throughout the three treatment cohorts. In summary, our results suggest that the reduction of BAT thermogenesis plays an important role during the long-term of olanzapine-induced weight gain, which was accompanied by an earlier onset of BAT adipocyte morphological changes and biochemical changes in the hypothalamus and the brainstem, while locomotor activity contributes to the entire olanzapine treatment courses. PMID:24548587

  3. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

  4. Spreading Waves of a Reduced Diffusion Coefficient of Water in Normal and Ischemic Rat Brain

    Microsoft Academic Search

    Yasuhiro Hasegawa; Lawrence L. Latour; James E. Formato; Christopher H. Sotak; Marc Fisher

    1995-01-01

    Summary: Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex.

  5. Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

    PubMed Central

    Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

    2015-01-01

    AIM: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. METHODS: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4?°C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1?, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. RESULTS: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD+ (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1?, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration. CONCLUSION: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model. PMID:26185373

  6. N-Acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure

    SciTech Connect

    Pinho, R.A.; Silveira, P.C.L.; Silva, L.A.; Streck, E.L.; Dal-Pizzol, F.; Moreira, J.C.F.

    2005-11-01

    Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8), and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n = 8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust.

  7. A self-assembling nanomaterial reduces acute brain injury and enhances functional recovery in a rat model of intracerebral hemorrhage.

    PubMed

    Sang, Lynn Yan-Hua; Liang, Yu-Xiang; Li, Yue; Wong, Wai-Man; Tay, David Kiong-Chiu; So, Kwok-Fai; Ellis-Behnke, Rutledge G; Wu, Wutian; Cheung, Raymond Tak-Fai

    2015-04-01

    There is no effective treatment for intracerebral hemorrhage (ICH). Intracerebral delivery of nanomaterials into the hemorrhagic lesion may be a new therapeutic strategy. In a rat model of ICH plus ultra-early hematoma aspiration, we found that locally delivered self-assembling peptide nanofiber scaffold (SAPNS) replaced the hematoma, reduced acute brain injury and brain cavity formation, and improved sensorimotor functional recovery. SAPNS serves as biocompatible material in the hemorrhagic brain cavity. Local delivery of this nanomaterial may facilitate the repair of ICH related brain injury and functional recovery. From the clinical editor: In a rat model of intracranial hemorrhage, these authors demonstrate that following ultra-early hematoma aspiration, local delivery of a self-assembling peptide nanofiber scaffold replaces the hematoma, reduces brain cavity formation, and improves sensorimotor functional recovery. Similar approaches would be welcome additions to the clinical treatment of this often devastating condition. PMID:24907463

  8. Vitamin E and probucol reduce urinary lipophilic aldehydes and renal enlargement in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Song-Suk Kim; D. D. Gallaher; A. Saari Csallany

    2000-01-01

    Diabetes mellitus is characterized by complications affecting several organs, including the kidney. Lipid peroxidation increases\\u000a in diabetes and has been implicated in the pathogenesis of diabetic complications. In this study, we examined the ability\\u000a of two antioxidants, vitamin E and probucol, to reduce lipid peroxidation in vivo and renal hypertrophy, an early stage of diabetic nephropathy, in rats. Animals were

  9. Malanga (Xanthosoma sagittifolium) and Purslane (Portulaca oleracea) Leaves Reduce Oxidative Stress in Vitamin A-Deficient Rats

    Microsoft Academic Search

    Sandra F. Arruda; Egle M. A. Siqueira; Elizabeth M. T. Souza

    2004-01-01

    Aim: This study examined the ability of tropical vegetables to reduce oxidative stress induced by vitamin A deficiency. Methods: Vitamin A-deficient male Wistar rats were divided into four groups which were treated for 30 days with different diets: AIN-93G vitamin A-deficient diet (DD), DD supplemented with pure ?-carotene (?-D) and DD supplemented with malanga (Xanthosoma sagittifolium) (MD) or purslane (Portulaca

  10. Evidence that High-sucrose DietReduces Dentin Formation andDisturbs Mineralization inRatMolars

    Microsoft Academic Search

    E.-L. Hietalal

    Inaddition toitscaries-promoting effect, ahigh- sucrose diet reduces theapposition ofmineralized dentin in youngrats. Thisstudy wasundertaken totest whether ithas asimilar effect onthewidthoftheas-yet-uncalcifi ed matrix, predentin. Female Wistar rats wereweanedattheageof3 weeksandfedfor7weekswitheither ahigh-sucrose diet, a non-cariogenic rawpotato starch diet, oranon-cariogenic commercial powdered ratfood(for reference). Thesucrose diet induced thegreatest numberofcaries lesions. Dentin formation wassmaller andthepredentin zonewider inrats fedasucrose diet whencompared withrats fedthereference diet. Inrats fedastarch

  11. Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model

    PubMed Central

    QI, CHEN; XU, MINGXIN; GAN, JING; YANG, XINXIN; WU, NA; SONG, LU; YUAN, WEIEN; LIU, ZHENGUO

    2014-01-01

    The purpose of this study was to determine the effectiveness of the systemic administration of high dose erythropoietin (EPO) in a 6-hydroxydopamine (6-OHDA)- induced rat model. Rats were divided into 7 groups. Groups 1–4 were administered daily EPO doses of 0; 2,500; 5,000 and 10,000 U/kg via intraperitoneal injection (i.p.) for 5 days. The EPO concentration in cerebrospinal fluid (CSF) was determined by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The dose of 10,000 U/kg was then selected for subsequent experiments. In group 5, rats received saline via medial forebrain bundle (MFB). In group 6, rats received 6-OHDA via MFB. In group 7, an EPO concentration of 10,000 U/kg was constantly administered i.p. for 5 days to rats prior to 6-OHDA injection via MFB. Behavioral analysis was performed for groups 5–7 by rat rotation tests. The number of tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN) was measured by immunocytochemistry. The activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases (MAPKs) and caspase-3 signaling in rats were analyzed using western blotting. The results showed that there was a significant increase in EPO levels in the CSF in 10,000 U/kg group compared with the 2,500 and 5,000 U/kg groups (P<0.01). Significantly fewer rotational counts were obtained in rats that were pretreated with EPO compared with saline-pretreated 6-OHDA-lesioned rats (P<0.001). The dopaminergic neurons in the 6-OHDA-lesioned SN were also increased in the EPO-pretreated rats when compared with control rats (P<0.01). Western blot analysis revealed that EPO inhibited the 6-OHDA-induced activation of JNK, ERK, p38 MAPK and caspase-3 signaling in the rat model. In conclusion, systemic administration of a high dose of EPO exerted neuroprotective effects in reversing behavioral deficits associated with Parkinson’s disease and prevented loss of the dopaminergic neurons through the MAPK pathway. PMID:24939444

  12. Milk-soluble formula increases food intake and reduces Il6 expression in elderly rat hypothalami.

    PubMed

    Ould Hamouda, Hassina; Delplanque, Bernadette; Benomar, Yacir; Crépin, Delphine; Riffault, Laure; LeRuyet, Pascale; Bonhomme, Cécile; Taouis, Mohammed

    2015-07-01

    Malnutrition in the elderly is accompanied by several metabolic dysfunctions, especially alterations in energy homeostasis regulation and a loss of insulin responsiveness. Nutritional recommendations aim to enrich food with high protein and energy supplements, and protein composition and lipid quality have been widely studied. Despite the numerous studies that have examined attempts to overcome malnutrition in the elderly through such nutritional supplementation, it is still necessary to study the effects of a combination of protein, lipids, and vitamin D (VitD). This can be done in animal models of elderly malnutrition. In the present study, we investigated the effects of several diet formulae on insulin responsiveness, inflammation, and the hypothalamic expression of key genes that are involved in energy homeostasis control. To mimic elderly malnutrition in humans, elderly Wistar rats were food restricted (R, -50%) for 12 weeks and then refed for 4 weeks with one of four different isocaloric diets: a control diet; a diet where milk soluble protein (MSP) replaced casein; a blend of milk fat, rapeseed, and DHA (MRD); or a full formula (FF) diet that combined MSP and a blend of MRD (FF). All of the refeeding diets contained VitD. We concluded that: i) food restriction led to the upregulation of insulin receptor in liver and adipose tissue accompanied by increased Tnf? in the hypothalamus; ii) in all of the refed groups, refeeding led to similar body weight gain during the refeeding period; and iii) refeeding with MSP and MRD diets induced higher food intake on the fourth week of refeeding, and this increase was associated with reduced hypothalamic interleukin 6 expression. PMID:25994005

  13. A leukocyte elastase inhibitor reduces thrombin-induced pulmonary oedema in the rat: mechanisms of action.

    PubMed

    Ahn, C M; Sandler, H; Saldeen, T

    1998-01-01

    The effect of a selective leukocyte elastase inhibitor, ICI 200,355, on thrombin-induced pulmonary oedema was studied in rats. Thrombin administration produced an increase in lung weight (P < 0.05), wet weight/ dry weight ratio (P < 0.05), and relative lung water content (P < 0.05). The lung weight increase was reduced by the elastase inhibitor in doses of 2000, 200 and 20 micrograms/kg per h (P < 0.05), but not by 2 micrograms/kg per h. A dose of 20 micrograms/ kg per h seems to be optimal, since 10-fold and 100-fold increases in dose did not further improve the effect. Free elastase activity in lung tissue was higher after thrombin infusion than in controls, but was not depleted by the elastase inhibitor in vivo (P < 0.05). This elastase activity in the lung was, however, inhibited by the elastase inhibitor in vitro, indicating that the inhibitor can block extracellular, but not intracellular elastase activity. Thrombin infusion resulted in a significant decrease in plasma elastase inhibitory capacity (P < 0.05), which was depleted by the elastase inhibitor (20 micrograms/kg per h) (P < 0.05). Myeloperoxidase activity was significantly increased in lung tissue after thrombin infusion (P < 0.05). Lung myeloperoxidase activity 5 min after thrombin infusion was not affected by the elastase inhibitor, but the inhibitor induced a further increase in myeloperoxidase as seen 90 min after thrombin infusion, indicating that the effect of this inhibitor on pulmonary oedema is not due to reduction of leukocyte infiltration in the lungs, but may partly be exerted by prevention of neutrophil destruction. PMID:10101747

  14. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    PubMed Central

    Cole, Jeffrey T.; Kean, William S.; Pollard, Harvey B.; Verma, Ajay; Watson, William D.

    2012-01-01

    Brain cells expend large amounts of energy sequestering calcium (Ca2+), while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum (ER) to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA). Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi) coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1–10 mM). The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity. PMID:22529775

  15. Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats.

    PubMed

    Redondo-Castro, Elena; Navarro, Xavier

    2014-02-01

    Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modulation of glial activity. These effects have boosted the use of ibuprofen as a tool to promote axonal regeneration and to increase functional recovery after neural injuries, although with controversial results showing positive and negative outcomes of ibuprofen treatment in several experimental models. We have evaluated the effects of ibuprofen administered at 60 mg/kg twice a day to rats subjected to a mild spinal cord contusion. Our results indicate that ibuprofen ameliorates mechanical hyperalgesia in rats by reducing central hyperexcitability, but failed to produce improvements in the recovery of locomotion. Despite an early effect on reducing microglial reactivity, the ibuprofen treatment did not provide histological evidence of neuroprotection; indeed the volume of cord tissue spared rostral to the lesion was decreased in ibuprofen treated rats. In summary, the early modulation of neuroinflammation produced by the administration of ibuprofen seems to eventually lead to a worse resolution of detrimental events occurring in the secondary injury phase, but also to reduce the development of neuropathic pain. PMID:24246280

  16. Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

    SciTech Connect

    Tsujiuchi, Toshifumi [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)]. E-mail: ttujiuch@life.kindai.ac.jp; Shimizu, Kyoko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Onishi, Mariko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Sugata, Eriko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fujii, Hiromasa [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Toshio [RI Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Honoki, Kanya [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Fukushima, Nobuyuki [Laboratory of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2006-10-27

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, it has been reported that alterations of LPA receptor expression might be important in the malignant transformation of tumor cells. Therefore, to assess an involvement of DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we investigated the expression of the lpa1 gene and its DNA methylation patterns in rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the analysis of methylation status, bisulfite sequencing was performed with B103 and RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of brain and liver. The lpa1 expressed cells and tissues were all unmethylated in this region of lpa1. In contrast, both B103 and RH7777 cells were highly methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza 2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after 24 h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation was also observed in response to LPA in RH7777 cells, but not in untreated RH7777 cells. These results suggest that aberrant DNA methylation of the lpa1 gene may be involved in its reduced expression in rat tumor cells.

  17. Effect of FK506 in reducing scar formation by inducing fibroblast apoptosis after sciatic nerve injury in rats

    PubMed Central

    Que, J; Cao, Q; Sui, T; Du, S; Kong, D; Cao, X

    2013-01-01

    We previously demonstrated that FK506, a generally applied immunosuppressant in organ transplantation, could promote peripheral nerve regeneration through reducing scar formation. However, little is known about how FK506 reduces scar formation. Herein we investigated the influence of FK506 on fibroblast proliferation and its correlation with scar formation after sciatic nerve injury in rats, and further explored the effect of FK506 on fibroblast proliferation and apoptosis in vitro. Masson staining and immunohistochemistry revealed that scar area and fibroblast number in the nerve anastomosis of sciatic nerve-injured rats were significantly reduced after FK506 administration. The scar area had a significant positive correlation with the fibroblast number, as detected by linear correlation analysis. CCK-8 assay and flow cytometry indicated that FK506 also inhibited proliferation and induced apoptosis of fibroblasts in vitro. It was primarily phosphorylation of JNK and ERK that were activated during the apoptosis of fibroblast. Pretreatment of cells with JNK inhibitor, SP600125, or ERK inhibitor, PD98059, could inhibit FK506-induced fibroblast apoptosis, respectively. Moreover, simultaneous application of both inhibitors had additive roles in cell protection from apoptosis. These results suggest that FK506-induced fibroblast apoptosis contributes to the suppression of fibroblast proliferation and then results in the reduction of scar formation in sciatic nerve-injured rat, and that JNK and ERK are involved in FK506-induced fibroblast apoptosis. PMID:23470533

  18. Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model

    PubMed Central

    Lubbad, Loay; Öberg, Carl M; Dhanasekaran, Subramanian; Nemmar, Abderrahim; Hammad, Fayez; Pathan, Javed Y; Rippe, Bengt; Bakoush, Omran

    2015-01-01

    Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ?20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (?) for FITC-Ficoll (molecular radius 20–90 Ĺ) using size exclusion HPLC. The values of ? for FITC-Ficoll of radius >50 Ĺ were significantly increased in STZ-diabetic rats compared to age-matched controls (? for 50–69 Ĺ = 0.001 vs. 0.0002, and ? for 70–90 Ĺ = 0.0007 vs. 0.00006, P < 0.001), while ? for FITC-Ficoll <50 Ĺ tended to be lower in diabetic rats than in controls (? for 36–49 Ĺ = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes. PMID:26009635

  19. Neonatal Exendin-4 Leads to Protection from Reperfusion Injury and Reduced Rates of Oxidative Phosphorylation in the Adult Rat Heart

    PubMed Central

    Brown, Suzanne B.; Libonati, Joseph R.; Selak, Mary A.; Shannon, Richard P.

    2015-01-01

    Purpose Glucagon like peptide-1 (7-36) amide (GLP-1) is an incretin hormone with multiple salutary cardiovascular effects. A short course of the GLP-1 analogue Exendin-4 (Ex-4) in the neonatal period prevents the development of mitochondrial dysfunction and oxidative stress in a rat prone to obesity and diabetes. We sought to evaluate whether neonatal Ex-4 can exert the same effect in the normal rat heart, as well as whether Ex-4 could affect susceptibility to cardiac reperfusion injury. Methods After birth, Sprague Dawley rat pups were given either Ex-4 (1 nmole/kg body weight) or vehicle (1% BSA in 0.9% saline) subcutaneously for 6 days. Animals were studied at juvenile (4–6 weeks) and adult (8–9 months) ages. Using the Langendorff isolated perfused heart, cardiovascular function was assessed at baseline and following ischemia-reperfusion. Mitochondria were isolated from fresh heart tissue, and oxidative phosphorylation and calcium sequestration were analyzed. TBARS, MnSOD activity, and non-enzymatic anti-oxidant capacity were measured to assess the degree of oxidative stress present in the two groups. Results Both at the juvenile and adult age, Ex-4 treated rats demonstrated improved recovery from an ischemic insult. Rates of oxidative phosphorylation were globally reduced in adult, but not juvenile Ex-4 treated animals. Furthermore, mitochondria isolated from adult Ex-4 treated rats sequestered less calcium before undergoing the mitochondrial permeability transition. Oxidative stress did not differ between groups at any time point. Conclusion A short course of Exendin-4 in the neonatal period leads to protection from ischemic injury and a preconditioned mitochondrial phenotype in the adult rat. PMID:20582459

  20. Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.

    PubMed

    Park, T; Lee, K

    1998-01-01

    The effects of dietary taurine supplementation on plasma and hepatic lipid levels and phospholipid profiles were evaluated in rats fed a high-cholesterol or a cholesterol-free diet. Four groups of male rats were fed one of the following diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a HCHTD had significantly lower plasma levels of total cholesterol (32% reduction), LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and triglyceride were also significantly reduced in rats fed a HTD compared to rats fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats. Taurine supplementation to the CFD also significantly reduced the hepatic triglyceride concentration (43% decrease) and elevated hepatic free fatty acid levels (77% increase) compared to rats fed only a CFD. These results suggest that dietary taurine supplementation is both hypocholesterolemic and hypotriglyceridemic in rats whose body cholesterol status is high or normal. PMID:9635047

  1. Lack of Evidence for Direct Corticospinal Contributions to Control of the Ipsilateral Forelimb in Monkey

    PubMed Central

    Soteropoulos, Demetris S.; Edgley, Steve A.; Baker, Stuart N.

    2011-01-01

    Strong experimental evidence implicates the corticospinal tract in voluntary control of the contralateral forelimb. Its potential role in controlling the ipsilateral forelimb is less well understood, although anatomical projections to ipsilateral spinal circuits are identified. We investigated inputs to motoneurons innervating hand and forearm muscles from the ipsilateral corticospinal tract using multiple methods. Intracellular recordings from 62 motoneurons in three anaesthetized monkeys revealed no monosynaptic, and only one weak oligosynaptic excitatory post-synaptic potential following stimulation of the ipsilateral corticospinal tract. Single stimulus intracortical microstimulation of the primary motor cortex (M1) in awake animals failed to produce any responses in ipsilateral muscles. Strong stimulation (>500?A, single stimulus) of the majority of corticospinal axons at the medullary pyramids revealed only weak suppressions in ipsilateral muscles at longer latencies than the robust facilitations seen contralaterally. Spike triggered averaging of ipsilateral muscle activity from M1 neural discharge (184 cells) did not reveal any post-spike effects consistent with monosynaptic corticomotoneuronal connections. We also examined the activity of 191 M1 neurons during ipsilateral or contralateral ‘reach to precision grip’ movements. Many cells (67%) modulated their activity during ipsilateral limb movement trials (compared with 90% with contralateral trials), but timing of this activity was best correlated with weak muscle activity in the contralateral non-moving arm. We conclude that, in normal adults, any inputs to forelimb motoneurons from the ipsilateral corticospinal tract are weak and indirect, and that modulation of M1 cell firing seems to be related primarily to control of the contralateral limb. PMID:21813682

  2. All-Trans Retinoic Acid Reduces Joint Adhesion Formation: An Experimental Study in Rats

    PubMed Central

    Wang, Yuguang; Zhang, Chao; Cheng, Huan; Douglas, Patricia; Wang, Zhiqiang; Lu, Yun

    2015-01-01

    Background Intra-articular adhesion is a common complication in post-surgical knees. The formation of post-surgical joint adhesion could lead to serious conditions. All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A that has a wide range of biological activities. The aim of the study was to verify the effects of (ATRA) in preventing adhesions in the post-operative rat knee. Material/Methods Eighty healthy adult male Wistar rats underwent femoral condyle-exposing surgery. After surgery, cotton pads soaked with the vehicle or various concentrations of ATRA (0.1%, 0.05%, 0.025%) were applied to the surgery site for 5 min. The post-surgical knee joints were fixed with micro-Kirschner wires in a flexed position for 4 weeks. The rats were killed 4 weeks after surgery. The effect of ATRA on the prevention of intra-articular adhesion was evaluated using histological analyses, hydroxyproline content, visual score, and inflammatory factor activity evaluation. Results No obvious postoperative complications or signs of infection in the rats were observed. None of the rats died before the scheduled time. The rats in the 0.1% ATRA group showed better outcomes, as suggested by the visual scores, hydroxyproline contents, and inflammatory factors expressional levels, than the other 2 groups. The local application of 0.1% ATRA was able to suppress adhesions, collagen expression, and inflammatory activity in the post-surgical rat knees. Conclusions In the rat knee surgery model, the application of intra-articular ATRA was able to decrease intra-articular scar adhesion formation, collagen expression, and inflammatory activities. ATRA was found to work in a dose-dependent manner, with 0.1% being possible optimal concentration. PMID:26044570

  3. All-trans retinoic Acid reduces joint adhesion formation: an experimental study in rats.

    PubMed

    Wang, Yuguang; Zhang, Chao; Cheng, Huan; Douglas, Patricia; Wang, Zhiqiang; Lu, Yun

    2015-01-01

    BACKGROUND Intra-articular adhesion is a common complication in post-surgical knees. The formation of post-surgical joint adhesion could lead to serious conditions. All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A that has a wide range of biological activities. The aim of the study was to verify the effects of (ATRA) in preventing adhesions in the post-operative rat knee. MATERIAL AND METHODS Eighty healthy adult male Wistar rats underwent femoral condyle-exposing surgery. After surgery, cotton pads soaked with the vehicle or various concentrations of ATRA (0.1%, 0.05%, 0.025%) were applied to the surgery site for 5 min. The post-surgical knee joints were fixed with micro-Kirschner wires in a flexed position for 4 weeks. The rats were killed 4 weeks after surgery. The effect of ATRA on the prevention of intra-articular adhesion was evaluated using histological analyses, hydroxyproline content, visual score, and inflammatory factor activity evaluation. RESULTS No obvious postoperative complications or signs of infection in the rats were observed. None of the rats died before the scheduled time. The rats in the 0.1% ATRA group showed better outcomes, as suggested by the visual scores, hydroxyproline contents, and inflammatory factors expressional levels, than the other 2 groups. The local application of 0.1% ATRA was able to suppress adhesions, collagen expression, and inflammatory activity in the post-surgical rat knees. CONCLUSIONS In the rat knee surgery model, the application of intra-articular ATRA was able to decrease intra-articular scar adhesion formation, collagen expression, and inflammatory activities. ATRA was found to work in a dose-dependent manner, with 0.1% being possible optimal concentration. PMID:26044570

  4. Calpain inhibitor I reduces colon injury caused by dinitrobenzene sulphonic acid in the rat

    Microsoft Academic Search

    S Cuzzocrea; M C McDonald; E Mazzon; H Mota-Filipe; T Centorrino; M L Terranova; A Ciccolo; D Britti; A P Caputi; C Thiemermann

    2001-01-01

    BACKGROUND AND AIMSInflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis.METHODSColitis was induced in rats by intracolonic instillation of dinitrobenzene

  5. The Consumption of Hibiscus sabdariffa Dried Calyx Ethanolic Extract Reduced Lipid Profile in Rats

    Microsoft Academic Search

    Octavio Carvajal-Zarrabal; Stefan M. Waliszewski; Dulce Ma. Barradas-Dermitz; Zaida Orta-Flores; Patricia M. Hayward-Jones; Cirilo Nolasco-Hipólito; Ofelia Angulo-Guerrero; Ramón Sánchez-Ricańo; Rosa M. Infanzón; Patricia R. L. Trujillo

    2005-01-01

    The scientific basis for the statement that plants and their active constituents play an important role in the prevention\\u000a of chronic and degenerative diseases is continously advancing. The object of the present study was to evaluate the effect\\u000a of Hibiscus sabdariffa L. dried calyx ethanolic extract on the serum lipid profile of Sprague-Dawley rats. The rats were fed during 4

  6. Melatonin Reduces Lipid Peroxidation and Tissue Edema in Cerulein-Induced Acute Pancreatitis in Rats

    Microsoft Academic Search

    Wenbo Qi; Dun-Xian Tan; Russel J. Reiter; Seok Joong Kim; Lucien C. Manchester; Javier Cabrera; Rosa M. Sainz; Juan Carlos Mayo

    1999-01-01

    Since oxygen free radicals and lipidperoxidation have been implicated in the pathogenesis ofan early stage of acute pancreatitis, we examinedwhether melatonin, a recently discovered free-radicalscavenger, could attenuate pancreatic injury inSprague-Dawley rats with cerulein-induced pancreatitis.Acute pancreatitis was induced by four intraperitonealinjections of cerulein (50 µg\\/kg body wt) given at1-hr intervals. Thirty minutes after the lastcerulein injection, the rats were killed and

  7. Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat

    Microsoft Academic Search

    P. B. Jeppesen; S. Gregersen; S. E. D. Rolfsen; M. Jepsen; M. Colombo; A. Agger; J. Xiao; K. Hermansen

    2003-01-01

    Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure[ndash ]lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g [middot] kg[minus ]1 [middot] d[minus ]1 of stevioside (purity [gt ] 99.6%) for

  8. Forelimb muscle architecture and myosin isoform composition in the groundhog (Marmota monax).

    PubMed

    Rupert, Joseph E; Rose, Jacob A; Organ, Jason M; Butcher, Michael T

    2015-01-15

    Scratch-digging mammals are commonly described as having large, powerful forelimb muscles for applying high force to excavate earth, yet studies quantifying the architectural properties of the musculature are largely unavailable. To further test hypotheses about traits that represent specializations for scratch-digging, we quantified muscle architectural properties and myosin expression in the forelimb of the groundhog (Marmota monax), a digger that constructs semi-complex burrows. Architectural properties measured were muscle moment arm, muscle mass (MM), belly length (ML), fascicle length (l(F)), pennation angle and physiological cross-sectional area (PCSA), and these metrics were used to estimate maximum isometric force, joint torque and power. Myosin heavy chain (MHC) isoform composition was determined in selected forelimb muscles by SDS-PAGE and densitometry analysis. Groundhogs have large limb retractors and elbow extensors that are capable of applying moderately high torque at the shoulder and elbow joints, respectively. Most of these muscles (e.g. latissimus dorsi and pectoralis superficialis) have high l(F)/ML ratios, indicating substantial shortening ability and moderate power. The unipennate triceps brachii long head has the largest PCSA and is capable of the highest joint torque at both the shoulder and elbow joints. The carpal and digital flexors show greater pennation and shorter fascicle lengths than the limb retractors and elbow extensors, resulting in higher PCSA/MM ratios and force production capacity. Moreover, the digital flexors have the capacity for both appreciable fascicle shortening and force production, indicating high muscle work potential. Overall, the forelimb musculature of the groundhog is capable of relatively low sustained force and power, and these properties are consistent with the findings of a predominant expression of the MHC-2A isoform. Aside from the apparent modifications to the digital flexors, the collective muscle properties observed are consistent with its behavioral classification as a less-specialized burrower and these may be more representative of traits common to numerous rodents with burrowing habits or mammals with some fossorial ability. PMID:25452499

  9. Successful Transplantation of Reduced Sized Rat Alcoholic Fatty Livers Made Possible by Mobilization of Host Stem Cells

    PubMed Central

    Hisada, Masayuki; Ota, Yoshihiro; Zhang, Xiuying; Cameron, Andrew M; Gao, Bin; Montgomery, Robert A; Williams, George Melville; Sun, Zhaoli

    2015-01-01

    Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insuficiency was associated with transplant failure of whole grafts which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx. PMID:22994609

  10. Animal model for the study of methanol toxicity: Comparison of folate-reduced rat responses with published monkey data

    SciTech Connect

    Lee, E.W.; Garner, C.D.; Terzo, T.S. (General Motors North American Operations, Warren, MI (United States))

    1994-01-01

    We attempted to develop a rodent model that exhibits characteristics of human methanol toxicities such as acidosis and visual dysfunction, which are correlated with an accumulation of formate, a toxic metabolite of methanol. Initially three groups of Long-Evans rats with different levels of liver folate were prepared and examined for formate accumulation after methanol administration (3.5 g/kg). The folate-reduced (FR) rats prepared by feeding a folate-deficient diet with 1% succinylsulfathiazole yielded blood formate levels equivalent to those found in methanol-intoxicated humans and developed signs of the visual system toxicity (a manuscript on the latter aspect is in preparation). Responses of FR rats to a variety of methanol exposure scenarios were then investigated, and the results were compared with those reported in the literature for monkeys. Formate accumulation and/or lethality were used as toxic parameters for this comparative evaluation. In FR rats dosed orally with 3 g/kg, the blood formate concentration was 9.2 mmol/L at 24 h postadministration and increased to 15.6 mmol/L at 48 h. The same dose given to monkeys yielded a plateau of 7.4 mmol/L at 12 h after methanol administration, and stayed at this level for an additional 12 h. After a 6-h exposure to 1200 ppm and 2000 ppm methanol, the blood formate concentrations in FR rats were increased by 370% and 636% above the endogenous level, respectively. However, blood formate did not accumulate above the endogenous level when monkeys were exposed to methanol up to 2000 ppm for 6 h. Under acute inhalation exposure conditions, FR rats exposed to 3000 ppm methanol, 20 h/d, could not survive more than 4 d. Moreover, monkeys survived for more than 4 d even after an exposure to 10,000 ppm. Thus, these results indicate that FR rats are more sensitive to methanol challenges than monkeys, and suggest that the FR rat could be a congruous animal model for evaluating the health effects of methanol in humans.

  11. Notoginsenoside R1 reduces blood pressure in spontaneously hypertensive rats through a long non-coding RNA AK094457

    PubMed Central

    Yang, Ying; Xi, Peng; Xie, Yuan; Zhao, Cuimei; Xu, Jiahong; Jiang, Jinfa

    2015-01-01

    Notoginsenoside R1 (NR1) is the main bioactive component in panaxnotoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of NR1 on antihypertension and the underlying mechanisms are still not clear. This study is aim to investigate the effect and elicit the mechanism of NR1 in antihypertension. Firstly, to assess the ability of NR1 in antihypertension, NR1 was injected in spontaneously hypertensive rats (SHR) via the vena caudalis. Then we examined the rats systolic blood pressure and inducible nitric oxide synthase (iNOS) activation in rats thoracoabdominal aortic. To further investigate the molecular mechanism of NR1 reduce blood pressure, primary SHR and WYK rat vascular endothelial cells (RVECs) were used for next study. LncRNAs related to hypertension were gained from bioinformatics analysis. The role of LncRNAs was finally characterized in RVECs by siRNA. Our results showed that NR1 significantly reduce blood pressure in SHR and induce nitric oxide (NO) generation through increasing the phosphorylation of iNOS. Through bioinformatics analysis and knockdown LncRNA AK094457 in RVECs, we also found LncRNA AK094457 promoted iNOS expression and NO concentration. Thus, we conclude that NR1 reduces the caudal blood pressure of SHR through induction of iNOS regulated by long non-coding RNA AK094457. These findings may have important implications for understanding the mechanisms of NR1 regulation blood pressure. PMID:26045775

  12. Reducing effect of the Chinese medicinal herb, Salvia miltiorrhiza, on alcohol self-administration in Sardinian alcohol-preferring rats.

    PubMed

    Maccioni, Paola; Vargiolu, Daniela; Falchi, Maura; Morazzoni, Paolo; Riva, Antonella; Cabri, Walter; Carai, Mauro A M; Gessa, Gian Luigi; Colombo, Giancarlo

    2014-09-01

    The dried roots of Salvia miltiorrhiza are highly valued in Chinese folk medicine for use in the prevention and treatment of a series of ailments. Previous studies have demonstrated that administration of standardized extracts of S. miltiorrhiza selectively reduced excessive alcohol drinking and relapse-like drinking in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to extend these findings on the "anti-alcohol" properties of S. miltiorrhiza extracts to operant procedures of oral alcohol self-administration. Two independent groups of sP rats were trained to lever-respond on an FR4 schedule of reinforcement for alcohol (15%, v/v) or sucrose (1-3%, w/v) in daily 30 min sessions. Once responding had stabilized, rats were tested under the fixed ratio 4 (FR4) schedule of reinforcement (index of alcohol reinforcing properties) and the progressive ratio (PR) schedule of reinforcement (index of alcohol motivational properties). Treatment with S. miltiorrhiza extract (0, 50, 100, and 200 mg/kg, intragastrically [i.g.]) markedly reduced lever responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). No dose of S. miltiorrhiza extract altered any parameter of sucrose self-administration. These results a) demonstrate that treatment with S. miltiorrhiza extract selectively reduced the reinforcing and motivational properties of alcohol in sP rats and b) extend to operant procedures of alcohol self-administration previous data on the "anti-alcohol" effects of S. miltiorrhiza extracts. These data strengthen the notion that novel pharmacological approaches for treatment of alcohol use disorders may stem from natural substances. PMID:24998034

  13. Synaptogenesis and dendritic growth in the cortex opposite unilateral sensorimotor cortex damage in adult rats: a quantitative electron microscopic examination

    Microsoft Academic Search

    Theresa A. Jones; Jeffrey A. Kleim; William T. Greenough

    1996-01-01

    Unilateral lesions of the forelimb area of the sensorimotor cortex in adult rats resulted in time-dependent increases in the number of synapses per neuron and the volume and membrane surface area of dendritic processes per neuron within layer V of the contralateral motor cortex in comparison to sham-operated rats. Based on previous findings of a behavioral relationship with increased dendritic

  14. Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

    PubMed Central

    Andersen, Monica L; Martins, Raquel CS; Alvarenga, Tathiana AF; Antunes, Isabela B; Papale, Ligia A; Tufik, Sergio

    2007-01-01

    Background Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. Conclusion Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain. PMID:17331246

  15. Efficacy of some antioxidants supplementation in reducing oxidative stress post sodium tungstate exposure in male wistar rats.

    PubMed

    Sachdeva, S; Flora, S J S

    2014-04-01

    This study aimed to evaluate the protective efficacy of some antioxidants against sodium tungstate induced oxidative stress in male wistar rats. Animals were sub-chronically exposed to sodium tungstate (100ppm in drinking water) for three months except for control group. In the same time, many rats were supplemented orally with different antioxidants (alpha-lipoic acid (ALA), n-acetylcysteine (NAC), quercetin or naringenin (0.30mM)) for five consecutive days a week for the same mentioned period before. Exposure to sodium tungstate significantly (P<0.05) inhibit blood ?-aminolevulinic acid dehydratase (ALAD) activity, liver and blood reduced glutathione (GSH) levels and an increase in oxidized glutathione (GSSG) and thiobarbituric acid reactive species (TBARS) levels in tissues. ALA acid and NAC supplementation post sodium tungstate exposure increased GSH and also, was beneficial in the recovery of altered superoxide dismutase and catalase activity, besides, significantly reducing blood and tissue reactive oxygen species and TBARS levels. The results suggest a more pronounced efficacy of ALA acid and NAC supplementation than quercetin or naringenin supplementation post sodium tungstate exposure in preventing induced oxidative stress in rats. PMID:24613855

  16. 17-hydroxyprogesterone caproate significantly improves clinical characteristics of preeclampsia in the reduced uterine perfusion pressure rat model.

    PubMed

    Amaral, Lorena M; Cornelius, Denise C; Harmon, Ashlyn; Moseley, Janae; Martin, James N; LaMarca, Babbette

    2015-01-01

    Preeclampsia is characterized by increased uterine artery resistance index, chronic immune activation, and decreased circulating nitric oxide levels. 17-?-Hydroxyprogesterone caproate (17-OHPC) is a synthetic metabolite of progesterone used for the prevention of recurrent preterm birth. We hypothesized that 17-OHPC could reduce mean arterial pressure by decreasing inflammation, whereas improving vasodilation by increasing nitric oxide bioavailability and uterine artery resistance index during late gestation in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. 17-OHPC (3.32 mg/kg) was intraperitoneally administered on gestation day 18 into RUPP rats, carotid catheters inserted, and mean arterial pressure, blood, and tissues were collected on day 19. Mean arterial pressure in normal pregnant (NP; n=13) was 92±2.0 and increased to123±2.0 in RUPP (n=18; P<0.0001), which was improved to 116±1.5 mm Hg in RUPP+17-OHPC (n=10; P<0.05). Circulating CD4+ T cells were 1.19%±1.0% of gated cells in NP (n=7), which increased to 8.52%±2.4% in RUPP rats (n=10; P<0.05) but was reduced to 2.72%±0.87% (n=14; P<0.05) in RUPP+17-OHPC. Circulating nitrate/nitrite was 26.34±3.5 µmol/L in NP (n=12) but was reduced to14.58±3.1 in RUPP rats (n=8; P=0.03) and increased to 22.69±1.62 in RUPP+17-OHPC (n=7; P=0.05). Endothelial nitric oxide synthase expression was 0.65±0.11 AU in NP (n=4), which decreased to 0.33±0.01 in RUPP rats (n=4; P=0.05) but increased to 0.57±0.01 in RUPP+17-OHPC (n=5; P=0.03). Uterine artery resistance index was 0.54±0.02 in NP (n=3), 0.78±0.03 in RUPP (n=4), and 0.63±0.038 in RUPP+17-OHPC (n=8; both P<0.05). Our findings demonstrate that even though modest, lowering blood pressure with 17-OHPC could be a viable treatment option for suppressing inflammation, uterine artery vasoconstriction while improving litter size. PMID:25368030

  17. Reduced sympathetic noradrenergic neurotransmission in the tail artery of Donryu rats fed with high cholesterol-supplemented diet

    PubMed Central

    Karoon, Parastoo; Burnstock, Geoffrey

    1998-01-01

    Sympathetic neurotransmission and noradrenaline content of the tail artery of Donryu rats fed for 2 months with a cholesterol-supplemented diet enriched with 4% cholesterol, 1% cholic acid, 0.5% thiouracil (CCT), were examined.Total serum cholesterol level of CCT fed rats (7.05±1.77?mg?ml?1, n=8) was significantly greater than lab-chow fed controls (2.58±0.32?mg?ml?1, n=8). Low density lipoprotein level was also significantly increased in CCT-fed (1.79±0.26?mg?ml?1, n=8) compared with control fed rats (1.35±0.25?mg?ml?1, n=8) but plasma levels of triglyceride and high density lipoproteins did not differ significantly between the two groups.Contractile responses of the arterial rings to transmural nerve stimulation (65 V, 0.1?ms, 4–64?Hz, 1?s), were markedly attenuated in the CCT fed animals compared with the controls. This reduction involved the noradrenergic rather than purinergic component of sympathetic transmission.Vasoconstrictor responses to exogenous noradrenaline (0.01–300??M) and adenosine 5?-triphosphate (0.3–1000??M) were unaffected by CCT diet, indicating prejunctional alteration of sympathetic neurotransmission during CCT-induced hyperlipidaemia.The noradrenaline content of the tail arteries of CCT fed animals (2.64±0.36?ng?mg?1, n=6) was significantly lower than that of controls (3.82±0.32?ng?mg?1, n=6).These findings show that chronic treatment of Donryu rats with a cholesterol-supplemented diet led to altered levels of circulating lipid fractions accompanied by attenuated sympathetic noradrenergic neurotransmission and reduced noradrenaline content of the rat tail artery. PMID:9535033

  18. Reduced sympathetic noradrenergic neurotransmission in the tail artery of Donryu rats fed with high cholesterol-supplemented diet.

    PubMed

    Karoon, P; Burnstock, G

    1998-03-01

    1. Sympathetic neurotransmission and noradrenaline content of the tail artery of Donryu rats fed for 2 months with a cholesterol-supplemented diet enriched with 4% cholesterol, 1% cholic acid, 0.5% thiouracil (CCT), were examined. 2. Total serum cholesterol level of CCT fed rats (7.05 +/- 1.77 mg ml(-1), n = 8) was significantly greater than lab-chow fed controls (2.58 +/- 0.32 mg ml(-1), n = 8). Low density lipoprotein level was also significantly increased in CCT-fed (1.79 +/- 0.26 mg ml(-1), n = 8) compared with control fed rats (1.35 +/- 0.25 mg ml(-1), n = 8) but plasma levels of triglyceride and high density lipoproteins did not differ significantly between the two groups. 3. Contractile responses of the arterial rings to transmural nerve stimulation (65 V, 0.1 ms, 4-64 Hz, 1 s), were markedly attenuated in the CCT fed animals compared with the controls. This reduction involved the noradrenergic rather than purinergic component of sympathetic transmission. 4. Vasoconstrictor responses to exogenous noradrenaline (0.01-300 microM) and adenosine 5'-triphosphate (0.3-1000 microM) were unaffected by CCT diet, indicating prejunctional alteration of sympathetic neurotransmission during CCT-induced hyperlipidaemia. 5. The noradrenaline content of the tail arteries of CCT fed animals (2.64 +/- 0.36 ng mg(-1), n = 6) was significantly lower than that of controls (3.82 +/- 0.32 ng mg(-1), n = 6). 6. These findings show that chronic treatment of Donryu rats with a cholesterol-supplemented diet led to altered levels of circulating lipid fractions accompanied by attenuated sympathetic noradrenergic neurotransmission and reduced noradrenaline content of the rat tail artery. PMID:9535033

  19. Yoghurts containing probiotics reduce disruption of the small intestinal barrier in methotrexate-treated rats.

    PubMed

    Southcott, E; Tooley, K L; Howarth, G S; Davidson, G P; Butler, R N

    2008-07-01

    Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow's milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep's milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days pre-MTX and 5 days post-MTX. Intestinal permeability was assessed on days -7, -1, 2, and 5 of the trial. Intestinal sections were collected at sacrifice for histological and biochemical analyses. Histology revealed that rats receiving CY and SY did not have a significantly damaged duodenum compared to controls. However, an improved small intestinal barrier function was evident, determined by a decreased lactulose/mannitol ratio. Probiotics containing SY and CY may be useful in preventing disruption to intestinal barrier function in MTX-induced mucositis. PMID:18427990

  20. In vivo transmission of impact shock waves in the distal forelimb of the horse.

    PubMed

    Gustĺs, P; Johnston, C; Roepstorff, L; Drevemo, S

    2001-04-01

    There is a high prevalence of lameness among Standardbred trotters, most commonly caused by noninfectious joint diseases, mainly related to training and competition. In this context, impact-related shock waves transmitted through the skeleton and joints have been proposed to be one important factor in the development of osteoarthritis. The aim of the present study was to investigate the characteristic pattern of the events immediately following first contact, with a focus on the in vivo transmission of impact shock waves in the distal forelimb. Two horses were trotted by hand over a force plate. Recordings of 3-D kinematics of the distal forelimb were carried out by use of a 240 Hz video system. Tri-axial accelerometer data were collected from a bone-mounted accelerometer on the midlateral side of the third metacarpal bone (McIII) and from another accelerometer attached to the lateral side of the hoof. Force plate and accelerometer data were sampled at 4.8 kHz using a 16-bit A/D-converter, synchronised with the kinematic data. The results indicate that the time lapse of the horizontal retardation of the hoof is an important factor in the attenuation of the impact. A shorter period of hoof braking showed higher amplitudes in the longitudinal retardation of McIII and a more rapid oscillation. This makes all parameters that affect the horizontal hoof braking potentially important to the orthopaedic health of the horse. PMID:11721549

  1. The antiepileptic drugs phenobarbital and carbamazepine reduce transport of methotrexate in rat choroid plexus by down-regulation of the reduced folate carrier.

    PubMed

    Halwachs, Sandra; Lakoma, Cathleen; Schäfer, Ingo; Seibel, Peter; Honscha, Walther

    2011-10-01

    Intrathecal methotrexate (MTX) has been associated with severe neurotoxicity. Because carrier-associated removal of MTX from the cerebrospinal fluid (CSF) into blood remains undefined, we determined the expression and function of MTX transporters in rat choroid plexus (CP). MTX neurotoxicity usually manifests as seizures requiring therapy with antiepileptic drugs (AEDs) such as phenobarbital (PB). Because we have demonstrated that PB reduces activity of MTX influx carrier reduced folate carrier (Rfc1) in liver, we investigated the influence of the AEDs PB, carbamazepine (CBZ), or gabapentin on Rfc1-mediated MTX transport in CP. Reverse transcriptase-polymerase chain reaction and Western blot analysis showed similar expression of the MTX influx carrier Rfc1 and organic anion transporter 3 or efflux transporter multidrug resistance-associated protein 1 (Mrp1) and breast cancer resistance protein (Bcrp) in rat CP tissue and choroidal epithelial Z310 cells. Confocal microscopy revealed subcellular localization of Rfc1 and Bcrp at the apical and of Mrp1 at the basolateral CP membrane. Uptake, efflux, and inhibition studies indicated MTX transport activity of Rfc1, Mrp1, and Bcrp. PB and CBZ but not gabapentin significantly inhibited Rfc1-mediated uptake of MTX in CP cells. Studies on the regulatory mechanism showed that PB significantly inhibited Rfc1 translation but did not alter carrier gene expression. Altogether, removal of intrathecal MTX across the blood-CSF barrier may be achieved through Rfc1-mediated uptake from the CSF followed by MTX extrusion into blood, particularly via Mrp1. Antiepileptic treatment with PB or CBZ causes post-transcriptional down-regulation of Rfc1 activity in CP. This mechanism may result in enhanced MTX toxicity in patients with cancer who are receiving intrathecal MTX chemotherapy by reduced CSF clearance of the drug. PMID:21737571

  2. Motor strategies used by rats spinalized at birth to maintain stance in response to imposed perturbations

    PubMed Central

    Giszter, Simon F; Davies, Michelle R; Graziani, Virginia

    2010-01-01

    Some rats spinalized P1/P2 achieve autonomous weight supported locomotion and quiet stance as adults. We used force platforms and robot applied perturbations to test such spinalized rats (n=6) which exhibited both weight supporting locomotion and stance, and also normal rats (n=8). Ground reaction forces in individual limbs, and the animals’ center of pressure were examined. In normal rats, both forelimbs and hindlimbs participated actively to control horizontal components of ground reaction forces. Rostral perturbations increased forelimb ground reaction forces, and caudal perturbations increased hindlimb ground reaction forces. Operate rats carried 60% body weight on the forelimbs and had a more rostral center of pressure placement. Normal rats pattern was to carry significantly more weight on the hindlimbs in quiet stance (~60%). Operate rats strategy of compensation for perturbations was entirely in forelimbs; as a result, the hind-limbs were largely isolated from the perturbation. Stiffness magnitude of the whole body was measured: its magnitude was hourglass shaped, with the principal axis oriented rostrocaudally. Operate rats were significantly less stiff; only 60-75% of normal rats’ stiffness. The injured rats adopt a stance strategy that isolates the hindlimbs from perturbation and may thus prevent hindlimb loadings. Such loadings could initiate reflex stepping, which we observed. This might activate lumbar pattern generators used in their locomotion. Adult spinalized rats never achieve independent hindlimb weight supported stance. The stance strategy of the P1 spinalized rats differed strongly from the behavior of intact rats and may be difficult for rats spinalized as adults to master. PMID:17287444

  3. Lactobionic acid reduces body weight gain in diet-induced obese rats by targeted inhibition of galectin-1.

    PubMed

    Mukherjee, Rajib; Yun, Jong Won

    2015-08-01

    Galectin-1 (GAL1), an animal lectin with a carbohydrate recognition domain, is known for its roles in cancer, tumor progression, as well as obesity and related complications. Here, we investigated the anti-obesity effect of lactobionic acid (LBA), a GAL1 inhibitor, both in vitro and in vivo. LBA treatment significantly reduced lipogenic capacity of both 3T3-L1 and HIB1B adipocytes through down-regulation of major adipogenic transcription factors at both mRNA and protein levels. Moreover, oral administration and intraperitoneal injection of LBA in Sprague-Dawley male rats fed a high fat diet caused marked reduction of body weight gain as well as improvement of related metabolic parameters. Important lipogenic transcription factors were also down-regulated in LBA-treated rats, resulting in attenuated lipogenesis and fat accumulation. Collectively, pharmaceutical targeting of GAL1 using LBA would be a novel therapeutic approach for the treatment of obesity. PMID:26116537

  4. Vitamin E attenuates cold-induced rat liver oxidative damage reducing H2O2 mitochondrial release.

    PubMed

    Venditti, P; Bari, A; Di Stefano, L; Di Meo, S

    2007-01-01

    Vitamin E is a major chain-breaking antioxidant which is able to reduce liver oxidative damage without modifying aerobic capacity in T(3)-treated rats. We investigated whether vitamin E has similar effects in hyperthyroid state induced by cold exposure. Cold exposure increased aerobic capacity and O(2) consumption in homogenates and mitochondria and tissue mitochondrial protein content. Vitamin E did not modify aerobic capacity and mitochondrial protein content of cold liver, but increased ADP-stimulated respiration of liver preparations. Succinate-supported H(2)O(2) release rates were increased by cold during basal and stimulated respiration, whereas the pyruvate/malate-supported ones increased only during basal respiration. Vitamin administration to cold-exposed rats decreased H(2)O(2) release rates with both substrates during basal respiration. This effect reduced ROS flow from mitochondria to cytosol, limiting liver oxidative damage. Cold exposure also increased mitochondrial capacity to remove H(2)O(2), which was reduced by vitamin treatment, showing that the antioxidant also lowers H(2)O(2) production rate. The different effects of cold exposure and vitamin treatment on H(2)O(2) generation were also found in the presence of respiration inhibitors. Although this can suggest that the cold and vitamin induce opposite changes in mitochondrial content of autoxidizable electron carriers, it is likely that vitamin effect is due to its capacity to scavenge superoxide radical. Finally, vitamin E reduced mitochondrial oxidative damage and susceptibility to oxidants, and prevented Ca(2+)-induced swelling elicited by cold. In the whole, our results suggest that vitamin E is able to maintain aerobic capacity and attenuate oxidative stress of hepatic tissue in cold-exposed rats modifying mitochondrial population characteristics. PMID:17553729

  5. Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat.

    PubMed

    Farooque, M; Isaksson, J; Jackson, D M; Olsson, Y

    1999-07-01

    Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 x 5.0 mm) for 5 min at T8-9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 +/- 4% in untreated animals but only to 38.5% +/- 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 +/- 2.7% in saline-treated injured animals and to 22.7 +/- 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord. PMID:10412797

  6. Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics.

    PubMed

    Madhu, P; Reddy, K Pratap; Reddy, P Sreenivasula

    2015-06-01

    This study was undertaken to investigate whether administration of melatonin protects PVB-Induced oxidative and metabolic toxicity in the liver of Wistar rats. Adult male Wistar rats were intraperitoneally injected with either melatonin or PVB (cisplatin, vinblastine, and bleomycin) alone or combination for a period of 9 weeks. A significant increase in lipid peroxidation levels and decrease in catalase and superoxide dismutase activity levels were observed in the liver mitochondria of rats treated with PVB indicating increased oxidative stress. PVB treatment significantly decreased the succinate dehydrogenase activity with a significant increase in lactate dehydrogenase, glucose-6-phosphate dehydrogenase, aspartate aminotransaminase, alanine aminotransaminase, and glutamate dehydrogenase activities indicating deranged hepatic metabolism. Melatonin administration, on the other hand was found to significantly improve PVB-Induced biochemical changes, bringing them closer to the controls. The results from the study provide evidence that treatment with PVB affects hepatic metabolism in rats by inducing oxidative stress followed by decreasing mitochondrial oxidation and also point towards the clinical potential of melatonin as an adjuvant therapy to conventional chemotherapeutic regimens. J. Exp. Zool. 323A: 301-308, 2015. © 2015 Wiley Periodicals, Inc. PMID:25755110

  7. Endotoxin-stimulated nitric oxide production increases injury and reduces rat liver chemiluminescence during reperfusion

    Microsoft Academic Search

    Tong T. Ma; Harry Ischiropoulos; Clifford A. Brass

    1995-01-01

    Background\\/Aims: Nitric oxide has many physiological functions and may play an important role in modulating tissue injury. However, the mechanism of NO action in ischemia\\/reperfusion injury is completely unknown. This report investigates the role of NO in hepatic reperfusion injury. Methods: Rat liver was oxygenated for 30 minutes, followed by 30 minutes of ischemia, and then reperfused for 30 minutes.

  8. Syzigium cumini seed extracts reduce tissue damage in diabetic rat brain

    Microsoft Academic Search

    P. Stanely Mainzen Prince; N. Kamalakkannan; Venugopal P. Menon

    2003-01-01

    Syzigium cumini commonly known as Jamun, is widely used in different parts of India for the treatment of diabetes mellitus. Oral administration of an aqueous Jamun seed extract (JSEt) for 6 weeks caused a significant decrease in lipids, thiobarbituric acid reactive substances (TBARS) and an increase in catalase and superoxide dismutase in the brain of alloxan induced diabetic rats. Oral

  9. Psyllium reduces relative calcium bioavailability and induces negative changes in bone composition in weanling Wistar rats

    Microsoft Academic Search

    Barbara H. D Luccia; M. Elizabeth Kunkel

    2002-01-01

    Certain dietary fibers may decrease calcium bioavailability. The objective of this study was to determine the bioavailability of calcium from different amounts and sources of psyllium. Psyllium fiber sources were purified powdered psyllium seed husk, Metamucil® brand fiber supplement, and All-Bran® Bran Buds® cereal. Sixty-six female weanling rats were fed diets containing 5% or 10% purified psyllium, 5% or 10%

  10. IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCING SERUM TESTOSTERONE AND EX VIVO TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to the androgen receptor (AR) antagonist vinclozolin. The current studies were designed to determine if IPRO would delay male rat pubertal development like vinclozolin and to identify the mechanism(s) of action...

  11. Evidence for reduced lymphatic CSF absorption in the H-Tx rat hydrocephalus model

    Microsoft Academic Search

    Matthias Rammling; Meenu Madan; Leena Paul; Babak Behnam; Jogi V Pattisapu

    2008-01-01

    BACKGROUND: There is mounting evidence that spinal fluid absorption takes place not only at the arachnoid villi, but also at several extracranial sites, which might serve as a reserve mechanism for, or be primarily involved in the absorption of CSF in hydrocephalus. METHODS: We compared the nasal lymphatic pathway in congenital Hydrocephalus-Texas (H-Tx) rats in unaffected and affected hydrocephalic (HC)

  12. Gastric saline infusion reduces ultrasonic vocalizations and brown fat activity in suckling rat pups.

    PubMed

    Nelson, Eric E; Alberts, Jeffrey R

    2002-03-01

    Under standard conditions involving isolation and cooling, it has been documented that intraoral infusion of milk and injection of the intestinal peptide cholecystokinin (CCK) result in an attenuation in ultrasonic vocalizations (USV) emitted by infant rat pups. One of the most effective stimuli in inhibiting ingestion in suckling rat pups is gastric distension, but the effect of gastric distension on USV production has not been reported. In this experiment, we subjected infant rats to intragastric infusion of isotonic saline (2% body weight) to produce a natural level of gastric distension and hydration. We found that this stimulus resulted in a powerful reduction in USV emissions in isolated 10-day-old rats. In a subsequent experiment, we found that gastric saline infusion also diminished brown adipose tissue (BAT) thermogenesis. There were different time courses of the gastric saline infusion effects on BAT thermogenesis and on USV emissions, however, suggesting that these processes may be independently regulated. We hypothesize that this stimulus induces a transient activation of the parasympathetic nervous system, which overrides the sympathetic control of BAT and USV production. PMID:11857330

  13. protein were dramatically reduced in the colonic mucosa of GF vs CV rats (respec-

    E-print Network

    Paris-Sud XI, Université de

    kinetics of a-linolenic acid were investigated in the human intestinal cell line Caco-2. Four clones (PD10 of mitochondrial HMG-CoA synthase in the intestinal mucosa of the adult rat. As opposed to what happens;-linolenic acid in human ente- rocyte-like Caco-2 cells. T Tranchant1,PT Tranchant P Besson C Hoinard J Delarue c

  14. Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

    Microsoft Academic Search

    Mariane Bertagnolli; Paulo C. Schenkel; Cristina Campos; Cristiano T. Mostarda; Dulce E. Casarini; Adriane Belló-Klein; Maria C. Irigoyen; Katya Rigatto

    2008-01-01

    BackgroundSpontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)-induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether

  15. Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat

    PubMed Central

    Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David

    2014-01-01

    Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

  16. Radioprotective Effect of Melatonin in Reducing Oxidative Stress in Rat Lenses

    PubMed Central

    Shirazi, Alireza; haddadi, Gholam Hasan; Asadi-Amoli, Fahimeh; Sakhaee, Saeideh; Ghazi-Khansari, Mahmoud; Avand, Abolghasem

    2011-01-01

    Objective: Ocular morbidity is widely observed when radiotherapy includes the orbit. Oxidative stress generated by irradiation is responsible for this complication. In different studies, it has been shown that melatonin has antioxidative properties and a radioprotective role. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury in rats' lenses after total cranial irradiation. Materials and Methods: Thirty-six adult female Sprague-Dawley rats were divided into six groups. Group I was the control group, group II only received total cranial gamma irradiation of 5 Gy, group III was exposed as the second group but at the dose of 8 Gy, group IV received 30 mg/kg melatonin 30 minutes prior to radiation plus total cranial irradiation of 5 Gy plus 5 mg/kg melatonin daily through intraperitoneal injection for ten days after irradiation, group V was treated similar to the fourth group, i.e. received irradiation plus melatonin, but at the dose of 8 Gy, and group VI only received melatonin (30 mg/kg on the first day and 5 mg/kg on the following days). Ten days after irradiation, all rats were sacrificed and their eyes were enucleated to measure the biochemical parameters i.e. malondialdehyde (MDA) and glutathione (GSH). Results: The levels of MDA in rat lenses increased and the levels of glutathione in lenses decreased after gamma ray irradiation but these parameters were still within normal limits in rats that received melatonin. Conclusion: It could be concluded that melatonin is useful in preventing radiation-induced oxidative injury due to its antioxidative and free radical scavenging properties. PMID:23508093

  17. Inhibition of microsomal triglyceride transfer protein improves insulin sensitivity and reduces atherogenic risk in Zucker fatty rats.

    PubMed

    Dhote, Vipin; Joharapurkar, Amit; Kshirsagar, Samadhan; Dhanesha, Nirav; Patel, Vishal; Patel, Avnish; Raval, Saurin; Jain, Mukul

    2011-05-01

    1. Insulin-resistant states are commonly associated with a significantly higher risk of atherosclerosis. Insulin resistance has also been correlated with enhanced very low-density lipoprotein (VLDL) production, which is exacerbated by increased intestinal lipid synthesis and insulin-stimulated de novo lipogenesis. Microsomal triglyceride transfer protein (MTP) catalyses the critical step in the synthesis and secretion of VLDL and chylomicrons. The purpose of the present study was to test the hypothesis that chronic inhibition of MTP with a small molecule inhibitor would improve insulin sensitivity and reduce atherogenic risk in a genetic model of diabetic dyslipidaemia. 2. The in vivo activity of BMS-201038, a potent inhibitor of MTP, was evaluated in a model of hypertriglyceridemia induced by Triton WR1339 and corn oil in Zucker fatty rats. Triglyceride secretion rate was significantly reduced by a single dose of BMS-201038 by 35% at 0.3 mg/kg and 47% at 1 mg/kg, respectively. 3. Another group of Zucker fatty rats was dosed orally with BMS-201038 (0.3 and 1 mg/kg) for 14 days. Serum levels of triglycerides were reduced by 71% and 87%, non-esterified free fatty acids were reduced by 33% and 40%, and low-density lipoproteins by 26% and 29%, by 0.3 mg/kg and 1 mg/kg dose of BMS-201038, respectively. These serum lipid changes were accompanied by significant improvements in glucose tolerance and insulin sensitivity. In addition, lipid peroxidation in liver was reduced by 59% and 61%, and superoxide dismutase activity was increased by 11% and 45% by 0.3 mg/kg and 1 mg/kg dose of BMS-201038, respectively. Similar beneficial changes were found in aorta as well. 4. The present study provides evidence that inhibition of MTP with a small molecule inhibitor significantly improves dyslipidaemia associated with insulin resistance and reduces the atherosclerotic risk. PMID:21401695

  18. Batroxobin protects against spinal cord injury in rats by promoting the expression of vascular endothelial growth factor to reduce apoptosis

    PubMed Central

    YU, HUI; LIN, BIN; HE, YONGZHI; ZHANG, WENBIN; XU, YANG

    2015-01-01

    The host response to spinal cord injury (SCI) can lead to an ischemic environment that can induce cell death. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions in order to reduce this cell death. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. We hypothesized in this study that batroxobin would exhibit protective effects following SCI by promoting the expression of VEGF to reduce the levels of apoptosis in a rat model of SCI. Ninety adult female Sprague Dawley rats were divided randomly into sham injury (group I), SCI (group II) and batroxobin treatment (group III) groups. The Basso-Bettie-Bresnahan (BBB) scores, number of apoptotic cells and expression of VEGF were assessed at 1, 3, 5, 7, 14 and 28 days post-injury. The BBB scores were significantly improved in group III compared with those in group II between days 5 and 28 post-injury (P<0.05). At each time-point subsequent to the injury, the number of apoptotic cells in group III was reduced compared with that in group II. Compared with group II, treatment with batroxobin significantly increased the expression of VEGF from day 3 until 2 weeks post-SCI (P<0.05), while no significant difference was observed at day 28. These data suggest that batroxobin has multiple beneficial effects on SCI, indicating a potential clinical application.

  19. Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups.

    PubMed

    Bagheri, Farzaneh; Goudarzi, Iran; Lashkarbolouki, Taghi; Elahdadi Salmani, Mahmoud

    2015-07-01

    Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4g/kg), group III received ethanol+melatonin (10mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum. PMID:25797213

  20. Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats.

    PubMed

    Iagher, Fabíola; de Brito Belo, Sérgio Ricardo; Naliwaiko, Katya; Franzói, Andressa Machado; de Brito, Gleisson Alisson Pereira; Yamazaki, Ricardo Key; Muritiba, Ana Lúcia; Muehlmann, Luis Alexandre; Steffani, Jovani Antonio; Fernandes, Luiz Cláudio

    2011-11-01

    We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia. PMID:21981555

  1. Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma.

    PubMed

    Matsushita, K; Kuramitsu, Y; Ohiro, Y; Obara, M; Kobayashi, M; Li, Y Q; Hosokawa, M

    1998-04-01

    Synergistic effects of active hexose correlated compound (AHCC) extracted from mushroom on the treatment with UFT against mammary adenocarcinoma, SST-2 cells, in congenitally T cell-depressed spontaneously hypertensive rats (SHR) were observed. AHCC plus UFT had slight but significant effects on the growth of primary tumors. Pulmonary metastases were not inhibited by the treatment with AHCC plus UFT, whereas metastases to axillary lymph nodes (LN) were obviously inhibited. Combination of AHCC plus UFT showed similar synergistic anti-metastatic effects in SHR rats with accelerated pulmonary metastases following the surgical removal of the primary tumors. In vitro studies demonstrated that AHCC plus UFT enhanced the NK cell activity in tumor-bearing rats, whereas UFT alone depressed the NK cell activity. AHCC plus UFT also enhanced the NO production and cytotoxicity of peritoneal macrophages. In addition, AHCC restored the suppressed mRNA expression of interleukin-1alpha and tumor necrosis factor-alpha induced by the chemotherapy. Taken together, the combination of AHCC plus UFT brought about good therapeutic effects not only on primary tumor growth but also on reducing metastasis and these effects were mediated by host immunity which was restored or activated by AHCC. AHCC may be a good candidate for a biological response modifier. PMID:9635925

  2. Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats

    PubMed Central

    Chen, Tie-Long; Zhu, Guang-Li; He, Xiao-Long; Wang, Jian-An; Wang, Yu; Qi, Guo-An

    2014-01-01

    Background: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. Methods: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. Results: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. Conclusions: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway. PMID:25663976

  3. Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Cai, Jing; Cao, Shenglong; Chen, Jingyin; Yan, Feng; Chen, Gao; Dai, Yuying

    2015-07-23

    This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague-Dawley rats (n=72) by endovascular perforation. Progesterone (8mg/kg or 16mg/kg) was administered to rats at 1, 6, and 12h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24h after experimental SAH. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH. PMID:26101829

  4. Nebivolol Reduces Proteinuria and Renal NADPH Oxidase-Generated Reactive Oxygen Species in the Transgenic Ren2 Rat

    PubMed Central

    Whaley-Connell, Adam; Habibi, Javad; Johnson, Megan; Tilmon, Roger; Rehmer, Nathan; Rehmer, Jenna; Wiedmeyer, Charles; Ferrario, Carlos M.; Sowers, James R.

    2009-01-01

    Background/Aims Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system activation are crucial in the pathogenesis of hypertension, cardiovascular and renal disease. NADPH oxidase-mediated increases in reactive oxygen species (ROS) are an important mediator for RAAS-induced cardiovascular and renal injury. Increased levels of ROS can diminish the bioactivity of nitric oxide (NO), a critical modulator of RAAS effects on the kidney. Thereby, we hypothesized that in vivo nebivolol therapy in a rodent model of activated RAAS would attenuate glomerular damage and proteinuria through its actions to reduce NADPH oxidase activity/ROS and increase bioavailable NO. Methods We utilized the transgenic Ren2 rat which displays heightened tissue RAAS, hypertension, and proteinuria. Ren2 rats (6–9 weeks of age) and age-matched Sprague-Dawley littermates were treated with nebivolol 10 mg/kg/day (osmotic mini-pump) for 21 days. Results Ren2 rats exhibited increases in systolic blood pressure, proteinuria, kidney cortical tissue total NADPH oxidase activity and subunits (Rac1, p67phox, and p47phox), ROS and 3-nitrotyrosine, as well as reductions in podocyte protein markers; each of these parameters improved with nebivolol treatment along with increases in renal endothelial NO synthase expression. Conclusions Our data suggest that nebivolol improves proteinuria through reductions in renal RAAS-mediated increases in NADPH oxidase/ROS and increases in bioavailable NO. PMID:19609077

  5. 15-deoxy-?12,14-prostaglandin J2 reduces albumin-induced arthritis in temporomandibular joint of rats.

    PubMed

    Silva Quinteiro, Mariana; Henrique Napimoga, Marcelo; Gomes Macedo, Cristina; Furtado Freitas, Fabiana; Balassini Abdalla, Henrique; Bonfante, Ricardo; Trindade Clemente-Napimoga, Juliana

    2014-10-01

    The aim of this study was to evaluate the peripheral effect of 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund?s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint. PMID:25016088

  6. Topographical investigations on the climbing fiber inputs from forelimb and hindlimb afferents to the cerebellar anterior lobe

    Microsoft Academic Search

    J. C. Eccles; L. Provini; P. Strata; H. Tábo?íková

    1968-01-01

    Summary  Volleys in group I and II fibers of muscle nerves and group II fibers of cutaneous, joint and fascial nerves have evoked CF responses in the anterior lobe of the cerebellum. In the pars intermedia there is a fairly sharp somatotopic localization of the forelimb CF responses to the Vth lobule (Larsell) and the hindlimb to the IVth and IIIrd

  7. Analysis of electrical potentials evoked in the cerebellar anterior lobe by stimulation of hindlimb and forelimb nerves

    Microsoft Academic Search

    J. C. Eccles; L. Provini; P. Strata; H. Tábo?íková

    1968-01-01

    Summary  Responses were evoked in the anterior lobe of the cerebellum by volleys in group I and II fibers of forelimb and hindlimb nerves — cutaneous, muscular, joint and fascial. These responses have been observed along microelectrode tracks that traverse the whole depth of the anterior lobe. These tracks have been identified in histological sections, and the recording sites along these

  8. Organization of the forelimb area in squirrel monkey motor cortex: representation of digit, wrist, and elbow muscles

    Microsoft Academic Search

    J. P. Donoghue; S. Leibovic; J. N. Sanes

    1992-01-01

    The EMG in 8 to 14 hand, forearm, and arm muscles evoked by intracortical electrical stimulation was recorded at 433 sites in layer V in the region of the forelimb area of the primary motor cortex (MI) of three squirrel monkeys during ketamine anesthesia. At each site, the EMG was recorded at movement threshold (T) and at 1.5T and 2T

  9. Differential spinal projections from the forelimb areas of the rostral and caudal subregions of primary motor cortex in the cat

    Microsoft Academic Search

    J. H. Martin

    1996-01-01

    We used anterograde transport of WGA-HRP to examine the topography of corticospinal projections from the forelimb areas within the rostral and caudal motor cortex subregions in the cat. We compared the pattern of these projections with those from the somatic sensory cortex. The principal finding of this study was that the laminar distribution of projections to the contralateral gray matter

  10. A bilateral cervical contusion injury model in mice: Assessment of gripping strength as a measure of forelimb motor function

    Microsoft Academic Search

    Roberto M. Aguilar; Oswald Steward

    2010-01-01

    Here, we describe a bilateral cervical contusion model for mice. Adult female mice received graded bilateral contusion injuries at cervical level 5 (C5) using a commercially available impactor (the IH device). Three separate experiments were carried out to define conditions that produce impairments in forelimb function without unacceptable impairment of general health. A grip strength meter (GSM) was used to

  11. Adolescent binge-like ethanol exposure reduces basal ?-MSH expression in the hypothalamus and the amygdala of adult rats

    PubMed Central

    Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E.; Cubero, Inmaculada

    2013-01-01

    Melanocortins (MC) are central peptides that have been implicated in the modulation of ethanol consumption. There is experimental evidence that chronic ethanol exposure reduces ?-MSH expression in limbic and hypothalamic brain regions and alters central pro-opiomelanocortin (POMC) mRNA activity in adult rats. Adolescence is a critical developmental period of high vulnerability in which ethanol exposure alters corticotropin releasing factor, neuropeptide Y, substance P and neurokinin neuropeptide activities, all of which have key roles in ethanol consumption. Given the involvement of MC and the endogenous inverse agonist AgRP in ethanol drinking, here we evaluate whether a binge-like pattern of ethanol treatment during adolescence has a relevant impact on basal and/or ethanol-stimulated ?-MSH and AgRP activities during adulthood. To this end, adolescent Sprague-Dawley rats (beginning at PND25) were pre-treated with either saline (SP group) or binge-like ethanol exposure (BEP group; 3.0 g/kg given in intraperitoneal (i.p.) injections) of one injection per day over two consecutive days, followed by 2 days without injections, repeated for a total of 8 injections. Following 25 ethanol-free days, we evaluated ?-MSH and AgRP immunoreactivity (IR) in the limbic and hypothalamic nuclei of adult rats (PND63) in response to ethanol (1.5 or 3.0 g/kg i.p.) and saline. We found that binge-like ethanol exposure during adolescence significantly reduced basal ?-MSH IR in the central nucleus of the amygdala (CeA), the arcuate nucleus (Arc) and the paraventricular nucleus of the hypothalamus (PVN) during adulthood. Additionally, acute ethanol elicited AgRP IR in the Arc. Rats given the adolescent ethanol treatment required higher doses of ethanol than saline-treated rats to express AgRP. In light of previous evidence that endogenous MC and AgRP regulate ethanol intake through MC-receptor signaling, we speculate that the ?-MSH and AgRP disturbances induced by binge-like ethanol exposure during adolescence may contribute to excessive ethanol consumption during adulthood. PMID:23792540

  12. Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat.

    PubMed

    Rispal-Padel, L; Meftah, E M

    1992-09-01

    1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5-3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1432056

  13. Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

    PubMed Central

    Weissenberg, R.; Lahav, M.; Raanani, P.; Singer, R.; Regev, A.; Sagiv, M.; Giler, S.; Theodor, E.

    1995-01-01

    Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7819047

  14. MT-7716, a potent NOP receptor agonist, preferentially reduces ethanol seeking and reinforcement in post-dependent rats.

    PubMed

    de Guglielmo, Giordano; Martin-Fardon, Rémi; Teshima, Koji; Ciccocioppo, Roberto; Weiss, Friedbert

    2015-07-01

    Dysregulation of the nociceptin (N/OFQ) system has been implicated in alcohol abuse and alcoholism, and growing evidence suggests that targeting this system may be beneficial for treating alcoholism. To further explore the treatment target potential of the N/OFQ system, the novel non-peptide, small-molecule N/OFQ (NOP) agonist MT-7716, (R)-2-{3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-N-methylacetamide hydrochloride hydrate, was examined for its effects on ethanol self-administration and stress-induced reinstatement of alcohol seeking in non-dependent and post-dependent rats. Male Wistar rats were trained to self-administer ethanol and then made ethanol dependent via repeated intragastric ethanol intubation. The effects of MT-7716 (0.3 and 1?mg/kg; PO) on alcohol self-administration were determined 2 weeks following dependence induction, when baseline self-administration was restored. Effects of MT-7716 on stress-induced reinstatement were tested in separate cohorts of rats, 1 and 3 weeks post-withdrawal. MT-7716 reduced alcohol self-administration and stress-induced reinstatement of alcohol seeking in post-dependent rats, but was ineffective in non-dependent animals. Moreover, the prevention of stress-induced reinstatement by MT-7716 was more pronounced at 3 weeks post-dependence. The results further confirm treatment target potential for the NOP receptor and identify non-peptide NOP agonists as promising potential treatment drugs for alcohol abuse and relapse prevention. The findings also support dysregulation of the N/OFQ system as a factor in alcohol seeking and reinforcement. PMID:24930632

  15. Ozonized sunflower oil reduces oxidative damage induced by indomethacin in rat gastric mucosa

    Microsoft Academic Search

    Z. Zamora; R. González; D. Guanche; N. Merino; S. Menéndez; F. Hernández; Y. Alonso; S. Schulz

    2008-01-01

    .\\u000a Objective and design:  This study was carried out in order to investigate the potential cytoprotective effects of ozonized sunflower oil (OSO) in\\u000a the damage of rat gastric mucosa induced by indomethacin and also to elucidate the role of reactive oxygen species (ROS),\\u000a lipid peroxidation and some constituents of antioxidant defense such as superoxide dismutase (SOD) and catalase (CAT) in these

  16. Upregulation of Atrial Natriuretic Peptide Gene Expression in Remnant Kidney of Rats with Reduced Renal Mass

    Microsoft Academic Search

    KAZUHITO TOTSUNE; HARALD S. MACKENZIE; HIROKO TOTSUNE; JULIA L. TROY; JONATHAN LYTTON; BARRY M. BRENNER

    1998-01-01

    Atrial natriuretic peptide (ANP) is synthesized in the kidney but its physiologic significance there is unclear. To determine whether renal expression of the ANP gene is regu- lated, renal ANP mRNA expression was assessed in remnant kidneys after 5\\/6 nephrectomy in Munich-Wistar rats. In nor- mal sodium intake groups, ANP mRNA expression in the remnant kidney was significantly increased by

  17. Manganese Porphyrin Reduces Retinal Injury Induced by Ocular Hypertension in Rats

    PubMed Central

    Dogan, Serdar; Unal, Mustafa; Ozturk, Nihal; Yargicoglu, Piraye; Cort, Aysegul; Spasojevic, Ivan; Batinic-Haberle, Ines; Aslan, Mutay

    2011-01-01

    This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP5+) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP5+ (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP5+ were measured via LC-MS/MS. Latencies of all VEP components (P1, N1, P2, N2, P3) were significantly prolonged (p<0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p<0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP5+ treatment and NOS inhibition in ocular hypertension. PMID:21669199

  18. Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets

    Microsoft Academic Search

    P. Y. Benhamou; C. Moriscot; M. J. Richard; O. Beatrix; L. Badet; F. Pattou; J. Kerr-Conte; J. Chroboczek; P. Lemarchand; S. Halimi

    1998-01-01

    Summary   Susceptibility of pancreatic islets to oxidant stress may affect islet viability and contribute to primary non function of\\u000a allo- or xenogenic grafts. We investigated the influence of overexpression of catalase (CAT) on the viability of human, porcine\\u000a and rat islets, as well as INS-1 beta-cell line. Islets were transfected with a replication-deficient adenovirus vector containing\\u000a human CAT cDNA under

  19. Reduced-size branch-line and rat-race hybrids for uniplanar MMIC's

    Microsoft Academic Search

    T. Hirota; A. Minakawa; M. Muraguchi

    1990-01-01

    A method of miniaturizing branch-line 90° hybrids and 180° rat-race hybrids is proposed. The method utilizes combinations of short high-impedance transmission lines and shunt lumped capacitors. The hybrids were fabricated on GaAs substrates and the validity and effectiveness of the method were confirmed through experiments at 25 GHz and 11 GHz. The fabricated hybrids demonstrate excellent design accuracy at high

  20. Vitamin A reduces lung granulomatous inflammation with eosinophilic and neutrophilic infiltration in Sephadex-treated rats

    Microsoft Academic Search

    Akiko Torii; Mio Miyake; Masashi Morishita; Komei Ito; Shinpei Torii; Tatsuo Sakamoto

    2004-01-01

    Vitamin A is known to suppress the activity of the transcription factors, nuclear factor-?B (NF-?B) and activator protein-1 (AP-1), as do glucocorticoids. The possibility that vitamin A exerts various anti-inflammatory effects therefore seems likely. Sephadex beads were administered intravenously to anesthesized rats pretreated with a subcutaneous injection of vitamin A (3000, 10,000, or 30,000 IU\\/kg) or vehicle once daily for

  1. Pretreatment with Simvastatin Reduces Lung Injury Related to Intestinal Ischemia-Reperfusion in Rats

    Microsoft Academic Search

    Arash Pirat; Pinar Zeyneloglu; Derya Aldemir; Selim Candan

    2006-01-01

    In this rat model study we evaluated whether pretreat- ment with simvastatin affects the severity of acute lung injury caused by intestinal ischemia-reperfusion (I\\/R). Twenty-four animals were randomly allocated to three equal groups (sham, control, simvastatin). The simva- statin group was pretreated with simvastatin 10 mg kg1 · day1 for 3 days, whereas the other groups received placebo. The simvastatin

  2. Antagonism of the melanocortin system reduces cold and mechanical allodynia in mononeuropathic rats

    Microsoft Academic Search

    W. H. Gispen; D. H. Vrinten; Gerbrand J. Groen; Roger A. H. Adan

    2000-01-01

    The presence of both pro-opiomelanocortin-derived peptides and melanocortin (MC) receptors in nociception-associated areas in the spinal cord suggests that, at the spinal level, the MC system might be involved in nociceptive transmission. In the present study, we demonstrate that a chronic constriction injury (CCI) to the rat sciatic nerve, a lesion that produces neuropathic pain, results in changes in the

  3. Liquid diets reduce cell proliferation but not neurogenesis in the adult rat hippocampus.

    PubMed

    Patten, A R; Moller, D J; Graham, J; Gil-Mohapel, J; Christie, B R

    2013-12-19

    Neurogenesis continues to occur in restricted regions of the brain throughout adulthood and can be modulated by dietary factors. Liquid or "soft" diets are commonly used for the administration of drugs in experimental models of disease, making it critical to determine whether dietary composition itself can affect neurogenesis. In this study Sprague-Dawley rats were fed either a liquid or a solid diet of identical composition from weaning until young adulthood. No differences in neuronal differentiation and survival of newly born cells were observed between rats that were fed a liquid diet and those that received a solid diet. However, a significant reduction in hippocampal cell proliferation was observed in the liquid diet-fed group, as assessed by the expression of two endogenous proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA). The method of feeding did not alter the basal function of the hypothalamic-pituitary-adrenal (HPA) axis in these animals, as no changes in circulating levels of corticosterone (CORT) were detected between liquid and solid diet-fed groups. There was also a significant reduction in cellular proliferation in the hypothalamus of liquid diet-fed rats, a brain region known to be involved in feeding-related behaviors. These findings indicate that liquid diets themselves can directly impact rates of cellular proliferation, but this does not seem to impact levels of overall neurogenesis in the adult brain. PMID:24060822

  4. Reduced Hippocampal Dentate Cell Proliferation and Impaired Spatial Memory Performance in Aged-Epileptic Rats

    PubMed Central

    Cavarsan, Clarissa F.; Queiroz, Claudio M.; dos Santos, Jair Guilherme; Xavier, Gilberto F.; Mello, Luiz Eugęnio; Covolan, Luciene

    2013-01-01

    Increased adult neurogenesis is observed after training in hippocampal-dependent tasks and also after acutely induced status epilepticus (SE) although the specific roles of these cells are still a matter of debate. In this study, we investigated hippocampal cell proliferation and differentiation and the spatial learning performance in young or aged chronically epileptic rats. Status was induced by pilocarpine in 3 or 20-month old rats. Either 2 or 20?months later, rats were treated with bromodeoxyuridine (BrdU) and subsequently underwent to 8-day schedule of water maze (WM) tests. As expected, learning curves were faster in young than in aged animals (P?

  5. Blockade of microglial activation reduces mechanical allodynia in rats with compression of the trigeminal ganglion.

    PubMed

    Han, Seung R; Yang, Gwi Y; Ahn, Myung H; Kim, Min J; Ju, Jin S; Bae, Yong C; Ahn, Dong K

    2012-01-10

    The present study investigated the role of microglia and p38 MAPK in the development of mechanical allodynia in rats with compression of the trigeminal ganglion. Male Sprague-Dawley rats weighing 250-260 g were used. Under pentobarbital sodium anesthesia, the animals were mounted onto a stereotaxic frame and given injections of 4% agar solution (10 ?L) to compress the trigeminal ganglion. The air-puff thresholds significantly decreased after compression of the trigeminal ganglion. On postoperative day 14, immunoreactivity to both OX-42 and p-p38 MAPK was up-regulated in the medullary dorsal horn as compared to the sham group. P-p38 MAPK was found to be co-localized with OX-42, but not with NeuN, a neuronal cell marker, or with GFAP, an astroglial cell marker. Intracisternal administration of 100 ?g of minocycline significantly inhibited both mechanical allodynia and activation of microglia produced by compression of the trigeminal ganglion. Intracisternal administration of 0.1, 1, or 10 ?g of SB203580, a p38 MAPK inhibitor, also significantly decreased mechanical allodynia and p38 MAPK activation in the trigeminal ganglion-compressed group. These results suggest that activation of p38 MAPK in the microglia is an important step in the development of mechanical allodynia in rats with compression of the trigeminal ganglion and that the targeted blockade of microglial p38 MAPK pathway is a potentially important new treatment strategy for trigeminal neuralgia-like nociception. PMID:22019843

  6. Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats.

    PubMed

    Collier, Timothy J; Greene, James G; Felten, David L; Stevens, Suzanne Y; Collier, Kathy Steece

    2004-02-01

    In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats. PMID:14749139

  7. Reduced spleen natural killer cell activity in virally challenged iron-deficient rat pups

    SciTech Connect

    Lockwood, J.F.; Sherman, A.R.

    1986-03-01

    Neonatal iron deficiency has been shown to alter several aspects of immunity in rats. This study determined the effects of iron deficiency on cytotoxicity of virally-induced natural killer cells (NK) in spleen. Rats (n = 8-12/grp) were fed 6 (severe deficiency, SID), 10 (moderate deficiency, MID), or 250 (adequate iron status, AIS) ppm iron d 1 pregnancy through d 21 lactation. Litters were adjusted to 7 on d 2. On d 17 pups were challenged intraperitoneally with 5 x 10/sup 5/ plaque forming units of vaccinia virus. Spleens were collected 4 d later and cell suspensions prepared and pooled within each litter. After isolation of mononuclear cells on a Ficoll-Hypaque gradient, macrophages were removed, and the resulting lymphocytes were incubated with Cr/sup 51/ labelled Yac-1 target cells at effector:target ratios (E:T) of 10:1 and 50:1. Cytotoxicity of NK cells were measured after 4 and 16 hrs by the Cr/sup 51/ release assay. In SID and MID groups body weights, spleen weights, and hemoglobin levels were significantly lower than in AIS pups (p < 0.001). Spleen NK cell cytotoxicity was significantly impaired in SID and MID pups. Depending on the E:T and incubation time, SID and MID cells had activities 30-50% of AIS cells (p < 0.001). Both severe and moderate iron deficiency markedly impair the cytotoxic activity of spleen natural killer cells in suckling rats.

  8. Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

    PubMed Central

    Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi

    2015-01-01

    AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.

  9. Reducing effect of ingesting tannic acid on the absorption of iron, but not of zinc, copper and manganese by rats.

    PubMed

    Afsana, Kaosar; Shiga, Kazuki; Ishizuka, Satoshi; Hara, Hiroshi

    2004-03-01

    Interest in the beneficial effects of polyphenols, including tannic acid (TA), is increasing, although, these compounds also have adverse effects; for example, on the absorption of iron (Fe), and possibly other trace minerals. We examined the effect of a graded dose of TA on the absorption of Fe and compared with that of zinc (Zn), copper (Cu) and manganese (Mn) in rats. We also investigated the effect of TA on cecal fermentation which plays a role in absorption. In Experiment 1, to set the optimum dose of Fe, male Sprague-Dawley rats (weighing 70-90 g) after acclimatization were fed with different levels of dietary Fe (5, 10, 20, 30 and 35 mg/kg). We observed that the hematocrit (Ht), serum Fe concentration and transferrin saturation (%) were each reduced in those rats fed less than 20 mg/kg Fe in a dose-dependent manner. In Experiment 2, the rats were fed with test diets containing the minimum required level of Fe, 30 mg/kg diet, with (5, 10, 15 and 20 g/kg diet) or without TA for a period of three weeks. Feeding a diet containing more than 10 g TA/kg diet, but not 5 g TA/kg diet, reduced the hemoglobin concentration (Hb), Ht and serum Fe concentration due to decreased Fe absorption. In contrast, the Zn, Cu and Mn absorption was not affected by TA feeding. It is also demonstrated that liver Fe, but not the Zn, Cu and Mn contents, were lower in the TA groups than in the TA-free control group. Feeding TA slightly decreased the pH value of the cecal contents with an increase in the major short-chain fatty acid pool. About 15% of the ingested TA were recovered in the feces of each TA-fed group. Our results demonstrate that more than 10 g TA/kg diet induced anemia by reducing the Fe absorption, although there was no effect on the absorption of other important trace minerals. Our findings suggest that the usual intake of polyphenols is relatively safe, but that a high intake by supplementation or by dietary habit of tannin affects only the Fe level. PMID:15056891

  10. Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes.

    PubMed

    Goulopoulou, Styliani; Hannan, Johanna L; Matsumoto, Takayuki; Ogbi, Safia; Ergul, Adviye; Webb, R Clinton

    2015-07-15

    Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (activators). In this study, we hypothesized that resistance arteries from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats, GK) would have reduced vasodilatory responses to heme-dependent sGC activation and increased responses to heme-independent sGC activation compared with control rats (Wistar). Endothelium-dependent and -independent relaxation was assessed in isolated segments from mesenteric resistance arteries (MA) mounted in a wire myograph. GK MA had reduced responses to acetylcholine (pEC50: 7.96 ± 0.06 vs. 7.66 ± 0.05, P < 0.05) and sodium nitroprusside (pEC50: 8.34 ± 0.05 vs. 7.77 ± 0.04, P < 0.05). There were no group differences in 8-bromoguanosine cGMP-induced relaxation and protein kinase G1 expression (P > 0.05). GK MA had attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56 ± 0.05 vs. 6.93 ± 0.06, P < 0.05) and BAY 58-2667 (heme-independent sGC activator; pEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, P < 0.05) and increased sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, P < 0.05]. Isolated resistance arteries from female rats of reproductive age that spontaneously develop type 2 diabetes have increased sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and stimulators. PMID:25957216

  11. Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves.

    PubMed

    Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo

    2010-10-01

    The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO(3) per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb's LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 ?m) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb. PMID:21197231

  12. Neither Milk Production, Milk Transfer Nor Pup Growth Hormone Account for Reduced Body Weights of Rat Pups Reared In Hypergravity

    NASA Technical Reports Server (NTRS)

    Bear, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Studies spanning the gravity continuum from 0 to 2-g are revealing new insights into how mammalian reproduction and development may proceed in the microgravity of space. Rat pups reared from either conception or midgestation in hypergravity (hg) weigh 6-15% less than 1-g controls. In the present study we analyzed maternal and pup factors that may account for reduced body weight of hg reared pups. Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g, 1.75-g or 2.0-g. Prolaction (Prl) and oxytocin (OT) were measured in hg-exposed dams during either pregnancy (G20) or lactation (Postnatal day [P] 10). Gravity related differences in Prl were not observed whereas OT was depressed during lactation in hg dams relative to controls (p less than 0.05). Milk transfer measured during a discrete suckling episode was actually increased in hg-reared litters and comparable numbers of milk-letdowns were observed in the two conditions. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on growth hormone (GH) and insulin-like growth factors (IGFs). Plasma GH measured in P10 pups using enzyme immunoassay (EIA) was significantly elevated in hg pups relative to 1-g controls (mean +/- sd., ng/ml: 2.0-g, 10.6 [3.0], 1.5-g 8.9 [4.0], 1.0-g, 7.95 [3.1]). Together, these findings suggest that neither milk production, milk transfer nor pup GH play significant roles in reduced body weights of hg-reared pups. Studies underway are focused on insulin-like growth factors.

  13. Olive oil reduces oxidative damage in a 3-nitropropionic acid-induced Huntington's disease-like rat model.

    PubMed

    Tasset, I; Pontes, A J; Hinojosa, A J; de la Torre, R; Túnez, I

    2011-05-01

    Free radicals contribute to altered neuronal functions in neurodegenerative diseases and brain aging, by producing lipid- and other molecule-dependent modifications. The Mediterranean diet has been associated with a reduced risk of neurodegenerative disease. This study sought to verify whether extra-virgin olive oil (EVOO) exerted a brain antioxidant effect, protecting the brain against the oxidative stress caused by 3-nitropropionic acid (3NP). 3NP was administered intraperitoneally (i.p.) at a dose of 20 mg/kg body weight over four consecutive days. EVOO (representing 10% of calorie intake in the total standard daily diet of rats) and hydroxytyrosol (HT; 2.5 mg/kg body weight) were administered for 14 days. In all studied samples, 3NP caused a rise in lipid peroxides (LPO) and a reduction in glutathione (GSH) content. While the results showed that EVOO and HT reduces lipid peroxidation product levels and blocks the GSH depletion prompted by 3NP in both striatum and rest of the brain in Wistar rats. In addition, EVOO blocks and reverses the effect of 3NP on succinate dehydrogenase activity. In brief, the data obtained indicate that EVOO and HT act as a powerful brain antioxidant. PMID:21756531

  14. Overexpression of mitochondrial Hsp70/Hsp75 in rat brain protects mitochondria, reduces oxidative stress, and protects from focal ischemia

    PubMed Central

    Xu, Lijun; Voloboueva, Ludmila A; Ouyang, YiBing; Emery, John F; Giffard, Rona G

    2013-01-01

    Mitochondria are known to be central to the cell's response to ischemia, because of their role in energy generation, in free radical generation, and in the regulation of apoptosis. Heat shock protein 75 (Hsp75/Grp75/mortalin/TRAP1) is a member of the HSP70 chaperone family, which is targeted to mitochondria. Overexpression of Hsp75 was achieved in rat brain by DNA 7transfection, and expression was observed in both astrocytes and neurons. Rats were subjected to 100 mins middle cerebral artery occlusion followed by assessment of infarct volume, neurological score, mitochondrial function, and levels of oxidative stress at 24 h reperfusion. Overexpression of Hsp75 reduced infarct area from 44.6%±21.1% to 25.7%±12.1% and improved neurological outcome significantly. This was associated with improved mitochondrial function as shown by protection of complex IV activity, marked reduction of free radical generation detected by hydroethidine fluorescence, reduction of lipid peroxidation detected by 4-hydroxy-2-nonenol immunoreactivity, and increased preservation of ATP levels. This suggests that targeting mitochondria for protection may be a useful strategy to reduce ischemic brain injury. PMID:18985056

  15. Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

    PubMed Central

    Umeda, Tatsuya; Seki, Kazuhiko; Sato, Masa-aki; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

    2012-01-01

    Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. PMID:23112841

  16. Calcium and ?-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    PubMed Central

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, ?-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or ?-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  17. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    EPA Science Inventory

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

  18. Exercise-Induced Neuroprotection in the Spastic Han Wistar Rat: The Possible Role of Brain-Derived Neurotrophic Factor

    PubMed Central

    Van Kummer, Brooke H.; Cohen, Randy W.

    2015-01-01

    Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF) and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection. PMID:25710032

  19. Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra.

    PubMed

    Konieczny, Jolanta; Czarnecka, Anna; Lenda, Tomasz; Kami?ska, Kinga; Lorenc-Koci, El?bieta

    2014-03-15

    The aim of the study was to determine whether the dopamine (DA) precursor l-DOPA attenuates parkinsonian-like symptoms produced by the ubiquitin-proteasome system inhibitor lactacystin. Wistar rats were injected unilaterally with lactacystin (2.5 ?g/2 ?l) or 6-OHDA (8 ?g/2 ?l) into the substantia nigra (SN) pars compacta. Four weeks after the lesion, the animals were treated chronically with l-DOPA (25 or 50 mg/kg) for two weeks. During l-DOPA treatment, the lactacystin-treated rats were tested for catalepsy and forelimb asymmetry. Rotational behavior was evaluated after apomorphine (0.25 mg/kg) and l-DOPA in both PD models. After completion of experiments, the animals were killed and the levels of DA and its metabolites in the striatum and SN were assayed. We found that acute l-DOPA administration effectively decreased catalepsy and increased the use of the compromised forelimb in the cylinder test. However, the lactacystin group did not respond to apomorphine or acute l-DOPA administration in the rotational test. Repeated l-DOPA treatment produced contralateral rotations in both PD models, but the number of rotations was much greater in the 6-OHDA-lesioned rats. Both toxins markedly (>90%) reduced the levels of DA and its metabolites in the striatum and SN, while l-DOPA diminished these decreases, especially in the SN. By demonstrating the efficacy of l-DOPA in several behavioral tests, our study confirms the usefulness of the lactacystin lesion as a model of PD. However, marked differences in the rotational response to apomorphine and l-DOPA suggest different mechanisms of neurodegeneration evoked by lactacystin and 6-OHDA. PMID:24361083

  20. Targeting Müller Cell–Derived VEGF164 to Reduce Intravitreal Neovascularization in the Rat Model of Retinopathy of Prematurity

    PubMed Central

    Jiang, Yanchao; Wang, Haibo; Culp, David; Yang, Zhihong; Fotheringham, Lori; Flannery, John; Hammond, Scott; Kafri, Tal; Hartnett, M. Elizabeth

    2014-01-01

    Purpose. To determine whether knockdown of Müller cell–derived VEGFA-splice variant, VEGF164, which is upregulated in the rat retinopathy of prematurity (ROP) model, safely inhibits intravitreal neovascularization (IVNV). Methods. Short hairpin RNAs for VEGF164 (VEGF164.shRNAs) or luciferase.shRNA control were cloned into lentivectors with CD44 promoters that specifically target Müller cells. Knockdown efficiency, off-target effects, and specificity were tested in HEK reporter cell lines that expressed green fluorescent protein (GFP)-tagged VEGF164 or VEGF120 with flow cytometry or in rat Müller cells (rMC-1) by real-time PCR. In the rat oxygen-induced retinopathy (OIR) ROP model, pups received 1 ?L subretinal lentivector-driven luciferase.shRNA, VEGFA.shRNA, or VEGF164.shRNA at postnatal day 8 (P8). Analyses at P18 and P25 included: IVNV and avascular retina (AVA); retinal and serum VEGF (ELISA); density of phosphorylated VEGFR2 (p-VEGFR2) in lectin-labeled retinal endothelial cells (ECs; immunohistochemistry); TUNEL staining and thickness of inner nuclear (INL) and outer nuclear layers (ONL) in retinal cryosections; and pup weight gain. Results. In HEK reporter and in rMC-1 cells and in comparison to lucifferase.shRNA, VEGFA.shRNA reduced both VEGF120 and VEGF164, but VEGF164.shRNA only reduced VEGF164 and not VEGF120. Compared with luciferase.shRNA, VEGFA.shRNA and VEGF164.shRNA reduced retinal VEGF and IVNV without affecting AVA at P18 and P25. At P25, VEGF164.shRNA more effectively maintained IVNV inhibition than VEGFA.shRNA. VEGFA.shRNA and VEGF164.shRNA reduced pVEGFR2 in retinal ECs at P18, but VEGFA.shRNA increased it at P25. VEGFA.shRNA increased TUNEL+ cells at P18 and decreased ONL thickness at P18 and P25. VEGFA.shRNA and VEGF164.shRNA did not affect pup weight gain and serum VEGF. Conclusions. Short hairpin RNA to Müller cell VEGF164 maintained long-term inhibition of IVNV and limited cell death compared with shRNA to VEGFA. PMID:24425851

  1. Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats

    Microsoft Academic Search

    Márta Ágoston; Ferenc Örsi; Erzsébet Fehér; Krisztina Hagymási; Zsuzsa Orosz; Anna Blázovics; János Fehér; András Vereckei

    2003-01-01

    Several antioxidants have been shown to reduce lysosomal phospholipidosis, which is a potential mechanism of amiodarone toxicity, and prevent amiodarone toxicity by antioxidant and\\/or non-antioxidant mechanisms. The aim of this study was to test whether the co-administration of two structurally different antioxidants vitamin E and silymarin with amiodarone can reduce amiodarone-induced lysosomal phospholipidosis, and if yes, by reducing the tissue

  2. Bromocriptine reduces rat thyrotropin beta-subunit mRNA stability.

    PubMed

    Levy, A; Lightman, S L

    1990-01-01

    We have examined the effect of orally administered bromocriptine on TSH beta-subunit messenger (m)RNA in the anterior pituitary glands of Sprague-Dawley rats using in situ and dot-blot hybridization histochemistry. Quantitative in situ hybridization of pituitary sections demonstrated a 60% reduction in TSH beta-subunit mRNA probe binding from rats fed a diet containing bromocriptine 10 mg/kg/day. This was confirmed by dot-blot analysis of nuclear and cytoplasmic pituitary extracts from the same tissue. Hybridization of cytoplasmic extracts of pituitary cells cultured under actinomycin D-induced transcription arrest showed that part of the effect of bromocriptine appeared to be mediated through a change in TSH beta-subunit mRNA stability and implies that the acute influence of dopamine on TSH metabolism may be transduced by control of TSH beta-subunit mRNA catabolism. This suggests a mechanism by which cells with relatively stable tissue specific mRNAs appear to respond rapidly to hormonal effects at the transcriptional level. PMID:2319107

  3. Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood.

    PubMed

    Chowanadisai, Winyoo; Kelleher, Shannon L; Lönnerdal, Bo

    2005-07-01

    Prenatal and early postnatal zinc deficiency impairs learning and memory and these deficits persist into adulthood. A key modulator in this process may be the NMDA receptor; however, effects of zinc deficiency on the regulation of NMDA receptor activity are not well understood. Female Sprague-Dawley rats were fed diets containing 7 (zinc deficient, ZD), 10 (marginally zinc deficient, MZD) or 25 (control) mg Zn/g diet preconception through postnatal day (PN) 20, at which time pups were weaned onto their maternal or control diet. Regulation of NMDA receptor expression was examined at PN2, PN11, and PN65. At PN2, expression of whole brain NMDA receptor subunits NR1, NR2A, and NR2B was lower in pups from dams fed ZD and MZD compared to controls, as analyzed using relative RT-PCR and immunoblotting. At PN11, whole brain and hippocampi NR1, NR2A, NR2B and PSA-NCAM (polysialic acid-neural cell adhesion molecule) expression and the number of PSA-NCAM immunoreactive cells were lower in pups from dams fed ZD compared to controls. Whole brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations were lower in pups from dams fed ZD or both low zinc diets, respectively. Whole brain NR1 expression remained lower in previously zinc-deficient rats at PN65. These data indicate potential mechanisms through which developmental zinc deficiency can impair learning and memory later in life. PMID:15998301

  4. Fibrates reduce triacylglycerol content by upregulating adipose triglyceride lipase in the liver of rats.

    PubMed

    Karahashi, Minako; Hoshina, Miki; Yamazaki, Tohru; Sakamoto, Takeshi; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

    2013-01-01

    Hepatic triacylglycerol (TAG) homeostasis is maintained by carefully regulated balance between its synthesis and disposal. Impairment in this balance causes steatosis. The aims of this study were i) to uncover whether fibrates control TAG concentration through the action of adipose triglyceride lipase (ATGL) and ii) to compare the potency of the effects on ATGL expression and TAG concentration among fenofibrate, bezafibrate, and clofibric acid in the liver of rats. Treatments of rats with the three fibrates induced ATGL and concomitantly decreased hepatic TAG concentration. The upregulation of ATGL was likely mediated through the activation of peroxisome proliferator-activated receptor ?. Fibrates also expanded capacity of fatty acid ?-oxidation. Importantly, three fibric acids (fenofibric, bezafibric, and clofibric acids) that are active metabolites formed in the liver exhibited almost the same potency to elevate ATGL expression in vivo, despite the fact that there were considerable differences in this regard among fenofibrate, bezafibrate, and clofibric acid when compared on the basis of their dosage. These results suggest that ATGL represents a potential therapeutic target for ameliorating hepatic steatosis and that fibric acids are promising agents to ameliorate and/or protect against hepatic steatosis. PMID:24292381

  5. Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats

    PubMed Central

    Nakamoto, Hideko; Kaneki, Masao; Goto, Sataro; Shimokado, Kentaro; Kobayashi, Hiroyuki; Naito, Hisashi

    2015-01-01

    Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver. PMID:26172834

  6. Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats.

    PubMed

    Tsuzuki, Takamasa; Shinozaki, Shohei; Nakamoto, Hideko; Kaneki, Masao; Goto, Sataro; Shimokado, Kentaro; Kobayashi, Hiroyuki; Naito, Hisashi

    2015-01-01

    Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver. PMID:26172834

  7. Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression of fat oxidation genes in rats.

    PubMed

    Islam, Ajmila; Civitarese, Anthony E; Hesslink, Robert L; Gallaher, Daniel D

    2012-02-01

    Dietary interventions that reduce accumulation of body fat are of great interest. Consumption of viscous dietary fibers cause well-known positive metabolic effects, such as reductions in the postprandial glucose and insulin concentrations. However, their effect on body composition and fuel utilization has not been previously studied. To examine this, rats were fed a viscous nonfermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), for 6 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and fat pad weight. Plasma adipokines, AMP kinase activation, and enzyme and mRNA analysis of key regulators of energetics in liver and soleus muscle were measured. The HPMC diet significantly lowered percent body fat mass and increased percent lean body mass, compared to a cellulose-containing diet (no viscosity). Fasting leptin was reduced 42% and resistin 28% in the HPMC group compared to the cellulose group. Rats fed HPMC had greater activation of AMP kinase in liver and muscle and lower phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. mRNA expression in skeletal muscle was significantly increased for carnitine palmitoyltransferase 1B (CPT-1B), PPAR? coactivator 1?, PPAR? and uncoupling protein 3 (UCP3), as was citrate synthase (CS) activity, in the HPMC group relative to the cellulose group. These results indicate that viscous dietary fiber preserves lean body mass and reduces adiposity, possibly by increasing mitochondrial biogenesis and fatty acid oxidation in skeletal muscle, and thus represents a metabolic effect of viscous fiber not previously described. Thus, viscous dietary fiber may be a useful dietary component to assist in reduction of body fat. PMID:22095115

  8. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    PubMed Central

    Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; K?l?c, Mehmet

    2015-01-01

    Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1?mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine?xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

  9. Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

    PubMed Central

    Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

    1989-01-01

    The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

  10. Role of glucocorticoids in the response of rat leg muscles to reduced activity

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Tischler, Marc E.

    1986-01-01

    Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

  11. High doses of caffeine reduce in vivo osteogenic activity in prepubertal rats.

    PubMed

    Shin, Jiwon; Choi, Yuri; Kim, Jisook; Yu, A-Ram; Shin, Ji-Soo; Choi, Yun-Young; Roh, Jaesook

    2015-07-01

    Caffeine adversely affects endochondral ossification during fetal skeletal growth, and results in increased incidence of delayed and abnormal fetal skeletal development. Chronic caffeine intake also decreases growth hormone secretion. Thus, it is conceivable that caffeine may disrupt bone growth during the peripubertal period. This study aimed to investigate the impact of high-caffeine consumption on bone growth throughout puberty. A total of 51 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg(-1)  day(-1) for 4 weeks. After death, the final length and weight of leg bones were measured, and the tibia processed for histomorphometric analysis. Caffeine caused a significant decrease in body mass gain. This was accompanied with proportional decreases in lean body mass and body fat. In addition, bone mass and osteogenic activity in vivo were assessed using dual-energy X-ray absorptiometry and (18) F-NaF positron emission tomography. The results showed significant decreases of bone mass and in vivo osteogenic activity in the caffeine-fed groups. Rats fed with caffeine showed a significantly shorter and lighter tibia and femur and the vertebral column compared with controls. In addition, caffeine does not increase the width of the growth plates (GPs), it slows the rate at which the GP closes due to a slower rate of growth. These results demonstrated that caffeine altered osteogenic activity, leading to delayed peripubertal longitudinal bone growth and maturation. Given that osteogenic cells undergo dynamic changes in metabolic activity and that the pubertal growth spurt is mainly stimulated by growth hormone/insulin-like growth factor-1 and sex steroids during pubertal development, caffeine could suppress ossification by interfering with both physiological changes in hormonal secretion and osteogenic activity during this critical period. Further study will be needed to investigate the cellular/molecular mechanism by which caffeine affects osteogenesis using in vitro experimental models. PMID:26041429

  12. Folic acid supplementation reduces oxidative stress and hepatic toxicity in rats treated chronically with ethanol

    PubMed Central

    Lee, Soo-Jung; Kang, Myung-Hee

    2011-01-01

    Folate deficiency and hyperhomocysteinemia are found in most patients with alcoholic liver disease. Oxidative stress is one of the most important mechanisms contributing to homocysteine (Hcy)-induced tissue injury. However it has not been examined whether exogenous administration of folic acid attenuates oxidative stress and hepatic toxicity. The aim of this study was to investigate the in vivo effect of folic acid supplementation on oxidative stress and hepatic toxicity induced by chronic ethanol consumption. Wistar rats (n = 32) were divided into four groups and fed 0%, 12%, 36% ethanol, or 36% ethanol plus folic acid (10 mg folic acid/L) diets. After 5 weeks, chronic consumption of the 36% ethanol diet significantly increased plasma alanine transaminase (ALT) (P < 0.05) and aspartate transaminase (AST) (P < 0.05), triglycerides (TG) (P < 0.05), Hcy (P < 0.001), and low density lipoprotein conjugated dienes (CD) (P < 0.05) but decreased total radical-trapping antioxidant potential (TRAP) (P < 0.001). These changes were prevented partially by folic acid supplementation. The 12% ethanol diet had no apparent effect on most parameters. Plasma Hcy concentration was well correlated with plasma ALT (r = 0.612**), AST (r = 0.652*), CD (r = 0.495*), and TRAP (r = -0.486*). The results indicate that moderately elevated Hcy is associated with increased oxidative stress and liver injury in alcohol-fed rats, and suggests that folic acid supplementation appears to attenuate hepatic toxicity induced by chronic ethanol consumption possibly by decreasing oxidative stress. PMID:22259676

  13. Glucomannan reduces neutrophil free radical production in vitro and in rats with adjuvant arthritis.

    PubMed

    Drábiková, Katarína; Perecko, Tomás; Nosál, Radomír; Bauerová, Katarína; Ponist, Silvester; Mihalová, Danica; Kogan, Grigorij; Jancinová, Viera

    2009-06-01

    The effect of glucomannan (GM), a natural polysaccharide isolated from the yeast Candida utilis, on reactive oxygen species (ROS) generation in human neutrophils in vitro and in rats with Mycobacterium butyricum induced adjuvant arthritis (AA) was tested by the luminol/isoluminol-enhanced chemiluminescence (CL) method. In vitro, GM (500 microg/ml) significantly decreased spontaneous CL of human whole blood, while PMA (4beta-phorbol-12beta-myristate-alpha13acetate)-stimulated CL was decreased by GM in the concentrations of 100 and 500 microg/ml. To specify the site of action of GM, its effect on extra- and intracellular ROS generation in isolated neutrophils was evaluated. GM significantly decreased spontaneous and PMA-stimulated CL and it was more effective extracellularly than intracellularly. In vivo experiments included healthy animals as controls, arthritic animals without any drug administration, and arthritic animals with GM administration (once daily in the oral dose of 15 mg/kg, over a period of 28 days). On day 28, CL in whole blood, spleen and joint was monitored. Arthritic animals treated with GM showed decrease in spontaneous and PMA-stimulated CL of whole blood as well as CL of the joint, in comparison with untreated animals. The obtained findings demonstrated an antioxidant effect of GM in vitro and in rats with AA, which may be due to its free radical scavenger activity and to interaction with different receptors and/or modulation of postreceptor intracellular signalling pathways. The specific physicochemical parameters, such as structure of GM, its low molecular weight and good water solubility, play an important role in the above effects. PMID:19429472

  14. Corticofugal connections between the cerebral cortex and the vestibular nuclei in the rat.

    PubMed

    Nishiike, S; Guldin, W O; Bäurle, J

    2000-05-01

    The distribution of cortical efferent connections to the vestibular nuclei was quantitatively analyzed by means of retrograde axonal transport of horseradish peroxidase, wheat germ agglutinin-horseradish peroxidase, and Fast Blue in rats. The tracer substances were injected into the spinal vestibular nucleus (SpVe), the caudal part of the medial vestibular nucleus (MVe), and nucleus X of Brown Norwegian rats. Projections to the vestibular nuclei were revealed bilaterally, but predominantly contralaterally from five cortical areas: (1) the parietotemporal region (PT) which occupied the caudal two-thirds of the secondary somatosensory area and spread over the caudal part of the primary somatosensory area and the visceral cortex; (2) the anterior forelimb (AF) overlapping the anterior part of the forelimb area and the transitional zone; (3) the anterior hindlimb (AH) overlapping the anterior part of the hindlimb area and the transitional zone; (4) the lateral forelimb (LF) centered in the intercalated zone lateral to the forelimb area; and (5) the ventrotemporal region (VT) located at the ventral part of the temporal cortex. In addition to these cortical fields, the frontal cortex was found to project directly to the vestibular nuclei. These corticofugal projections were verified in experiments in which biocytin was injected into the rat PT. Anterogradely labelled fibers were traced predominantly contralaterally to the SpVe, caudal part of the MVe, and nucleus X. It is suggested that the rat corticofugal projections to the caudal vestibular nuclei modify vestibular reflexes to assist in coordinating eye, head and body movements during locomotion. PMID:10754508

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

    PubMed

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

    2011-11-01

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

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

    PubMed Central

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

    2011-01-01

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

  17. Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

    PubMed

    Erdely, Aaron; Antonini, James M; Young, Shih-Houng; Kashon, Michael L; Gu, Ja K; Hulderman, Tracy; Salmen, Rebecca; Meighan, Terence; Roberts, Jenny R; Zeidler-Erdely, Patti C

    2014-01-01

    Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

  18. Influence of oxidizing or reducing agents on gastrointestinal absorption of U, Pu, Am, Cm and Pm by rats

    SciTech Connect

    Sullivan, M.F.; Ruemmler, P.S.; Ryan, J.L.; Buschbom, R.L.

    1986-02-01

    Absorption of 233U, 238Pu, 241Am, and 244Cm from the gastrointestinal (GI) tract was measured in rats, fed ad libitum or fasted, that were gavaged with solutions containing ferric iron, ferrous iron, iron powder, quinhydrone or ascorbic acid. Absorption and retention of all of these actinides was increased substantially by fasting and by the addition of mild oxidizing agents, ferric iron and quinhydrone. In contrast, absorption and retention were decreased to below the fasted level by all the reducing agents except ascorbic acid, which caused diarrhea and an increase in absorption. Absorption of the lanthanide element 147Pm from the intestine of fasted rats was also increased by ferric iron. Some of these actinide elements are polyvalent and are, in some cases, known to be absorbed from the GI tract more readily in their higher oxidation states. This suggested an oxidation-reduction mechanism for the effect of fasting and the action of the chemical agents used. However, the improbability that either 241Am(III) 244Cm(III) or 147Pm is converted to a different oxidation state under these conditions makes that mechanism unlikely. Other explanations are suggested.

  19. Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats

    PubMed Central

    2014-01-01

    Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

  20. Unilateral injection of A?25-35 in the hippocampus reduces the number of dendritic spines in hyperglycemic rats.

    PubMed

    Lazcano, Zayda; Solis, Oscar; Bringas, María Elena; Limón, Daniel; Diaz, Alfonso; Espinosa, Blanca; García-Peláez, Isabel; Flores, Gonzalo; Guevara, Jorge

    2014-07-22

    Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several risk factors including impaired glucose metabolism in the brain that could cause molecular and neurochemical alterations in cognitive regions such as the hippocampus (Hp). Consequently, this process could cause neuronal morphological changes; however, the mechanism remains elusive. We induced chronic hyperglycemia after streptozotocin (STZ) administration. Then, we examined spatial learning and memory using the Morris water maze test and evaluated neuronal morphological changes using the Golgi-Cox stain procedure in hyperglycemic rats that received a A?25-35 unilateral injection into the Hp. Our results demonstrate that STZ combined with A?25-35 induced significant deficits in the spatial memory. In addition, we observed a significant reduction in the number of dendritic spines of pyramidal neurons in the dorsal Hp of rats with STZ plus A?25-35 . In conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp could produce the spatial memory deficit observed in these animals. These results suggest that hyperglycemia can trigger A?-induced neurodegeneration and thus the appearance of AD symptoms would be accelerated. Synapse, 2014. © 2014 Wiley Periodicals, Inc. PMID:25049192

  1. Irradiation of rat brain reduces P-glycoprotein expression and function

    Microsoft Academic Search

    J. Bart; W. B. Nagengast; R. P. Coppes; T. D. Wegman; H J M Groen; W. Vaalburg; E. G. F. de Vries; N. H. Hendrikse; EGE de Vries

    2007-01-01

    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

  2. Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

    PubMed Central

    Chen, Ya-Ling; Peng, Hsiang-Chi; Wang, Xiang-Dong

    2015-01-01

    Background In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. Results After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-? expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-?1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. Conclusions These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake.

  3. Brief Exposure to Novel or Enriched Environments Reduces Sucrose Cue-Reactivity and Consumption in Rats after 1 or 30 Days of Forced Abstinence from Self-Administration

    PubMed Central

    Grimm, Jeffrey W.; Weber, Rachel; Barnes, Jesse; Koerber, Jon; Dorsey, Kylan; Glueck, Edwin

    2013-01-01

    Environmental enrichment (EE) reduces drug and sucrose cue-reactivity in rats. In a previous study we reported that 1 month of EE (large cage, toys, and social cohorts) significantly reduced sucrose cue-reactivity. In the present study, we examined whether overnight (22 h) EE would be as effective. We also examined whether social enrichment (SE), enrichment alone (SoloEE), or exposure to an alternative environment (AEnv) might account for the EE effect. Rats self-administered 10% sucrose (.2 mL/delivery) in 10 daily 2-h sessions. Sucrose delivery was accompanied by a tone+light cue. Rats were then exposed to enrichment or alternative environment conditions overnight (acute) or for 29 days (chronic). Sucrose cue-reactivity was measured after this period of forced abstinence in a session identical to training, but no sucrose was delivered with the cue. All acute conditions markedly reduced sucrose cue-reactivity after 1 day of forced abstinence compared to single-housed rats in standard vivarium housing (CON). Sucrose consumption was also significantly reduced in all groups but SoloEE in a next-day test. All acute conditions but SE significantly reduced sucrose cue-reactivity when administered just prior to Day 30 of forced abstinence; all reduced sucrose consumption in a next-day test. All chronic conditions except for SE and AEnv significantly reduced sucrose cue-reactivity on the Day 30 test and sucrose consumption in a next day test. For both acute and chronic comparisons, EE manipulations were the most effective at reducing sucrose cue-reactivity and consumption. SoloEE and EE were equally effective at reducing sucrose cue-reactivity and similarly effective at reducing sucrose consumption. This indicates that social interaction is not a necessary condition for reducing sucrose-motivated behaviors. These results may be useful in the development of anti-relapse strategies for drug and food addictions. PMID:23342096

  4. Inhibition of postprandial hyperglycemia by either an insulin-dependent or -independent drug reduces the expression of genes related to inflammation in peripheral leukocytes of OLETF rats.

    PubMed

    Imai, Chihiro; Harazaki, Tomomi; Inoue, Seiya; Mochizuki, Kazuki; Goda, Toshinao

    2013-01-01

    Treatment with the dipeptidyl peptidase-4 inhibitor, anagliptin, or with the ?-glucosidase inhibitor, miglitol, reduced the oral sucrose load-inducible expression of interleukin (IL)-1?, IL-18, tumor necrosis factor-?, S100a8, S100a9, S100a11, IL-1R2, IL-1Rn and tumor necrosis factor receptor 2 genes in peripheral leukocytes of Otsuka Long-Evans Tokushima fatty (OLETF) rats at the stage of impaired glucose tolerance. Inhibiting postprandial hyperglycemia reduced the expression of genes related to inflammation in peripheral leukocytes of OLETF rats. PMID:24200798

  5. Elevated serum levels of T3 without metabolic effect in nutritionally deficient rats, attributable to reduced cellular uptake of T3

    SciTech Connect

    Okamura, K.; Taurog, A.; DiStefano, J.J.

    1981-08-01

    Rats receiving a nutritionally deficient diet displayed markedly elevated serum free T3 levels but showed no increase in oxygen consumption. This was associated with greatly reduced ratios of hepatic cellular and nuclear /sub 125/I-T3 to serum /sub 125/I-T3. Kinetic data supported the conclusion that cellular uptake of T3 was decreased in the nutritionally deficient rats. The lack of metabolic effect, despite the elevated serum T3 levels, is attributable to reduced availability of serum T3 to tissue nuclear receptor sites.

  6. Reduced Hippocampal Dendritic Spine Density and BDNF Expression following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Male Long Evans Rats

    PubMed Central

    Smith, Catherine A.; Holahan, Matthew R.

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats. PMID:25295592

  7. Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability.

    PubMed

    Youssef, Farid F

    2015-03-01

    Calorie restriction and the ketogenic diet have been successfully used in models of neuroprotection. However, there are limitations in clinical application of these diets and attention has turned to understanding their mechanism of action. Ketone bodies are produced in both diets and maybe involved in their ability to attenuate neuronal injury. This study seeks to assess the effects of ketone bodies on neuronal transmission and their efficacy in reducing the impact of known excitotoxins. We made use of extracellular recordings from rat hippocampal slices and demonstrate that ketone bodies had no effect on neuronal transmission or induction of long-term potentiation (LTP). Perfusion of slices with N-methyl-d-aspartate (NMDA, 15 ?M) produced neuronal depression suggestive of cell injury (antidromic recording also demonstrated similar depression), such that recovery of population spike potentials after 60 minutes was 27% in normal (10 mM) glucose but only 7% during reduced (2·5 mM) glucose availability. Experiments in ketone bodies demonstrated improved recovery (31%) but only under conditions of low glucose. Similarly, there was enhanced recovery of slices treated with kainic acid (KA, 30 ?M) in reduced glucose media (13-27%), but no difference in normal glucose. These findings suggest that ketone bodies do not alter neuronal function but can alter the response to excitotoxins when energy supplies are impaired, probably by acting as an alternative energy substrate. PMID:25082548

  8. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    PubMed

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, ?-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ? 0.001) and glutamate (467%, p ? 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. PMID:25578265

  9. Low-Level Laser Therapy (808 nm) Reduces Inflammatory Response and Oxidative Stress in Rat Tibialis Anterior Muscle After Cryolesion

    PubMed Central

    Assis, Lívia; Moretti, Ana I.S.; Abrahăo, Thalita B.; Cury, Vivian; Souza, Heraldo P.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2012-01-01

    Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n = 20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808 nm, tip area of 0.00785 cm2, power 30 mW, application time 47 seconds, fluence 180 J/cm2; 3.8 mW/cm2; and total energy 1.4 J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-k? and COX-2 and by TNF-? and IL-1? concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. PMID:23001637

  10. Failure of Intravenous Lipid Emulsion to Reduce Diazinon-induced Acute Toxicity: a Pilot Study in Rats

    PubMed Central

    Moshiri, Mohammad; Vahabzadeh, Maryam; Etemad, Leila; Hosseinzadeh, Hossein

    2013-01-01

    Diazinon (DZN) is a synthetic organophosphorus (OPs) insecticide widely used in agricultural and household applications. OPs, particularly DZN, are highly lipid soluble liquids. Intravenous lipid emulsion (ILE) has been shown to reduce toxicity caused by some lipid soluble agents. We evaluated the antidote effect of ILE on acute toxicity of DZN. Twenty-four Sprague-Dawley female rats weighting 200-250 g were treated orally with dose of 480 mg/ kg of DZN gavaged at the volume of 0.5 mL/kg. Thirty minutes after administration of DZN, two groups were treated by either ILE 10% (ILE10) or normal saline (NS) (16 mL/kg) (NS16) that were infused for the duration of 15 minutes. Another two groups were also treated by either ILE 20% (ILE20) or NS (10 mL/kg: NS10) as above. The changes in body weight, diarrhea score, muscular power, fasciculation, convulsions and mortality rate of the animals were all monitored immediately after infusions and then every 6 h up to 48 h. There was no significant difference in animals mean weight between different groups during the observation period. In addition, during the 48-hour observation we could not find any difference in muscular power and diarrhea score between groups of ILE20-NS10 and ILE10-NS16 in comparison with each other, and neither ILE 10% nor ILE %20 could not reduce mortality rate of animals or increase the survival time of rats. In conclusion, ILE seems to be unable to reverse DZN acute toxicity and it might be due to conversion of DZN to potent and less lipid soluble agent. PMID:24523769

  11. Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats

    PubMed Central

    Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Rio, Daniele Del; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

    2012-01-01

    Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n?=?128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n?=?54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n?=?64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention. PMID:22768138

  12. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain

    PubMed Central

    Ragavendran, J. Vaigunda; Laferričre, André; Xiao, Wen Hua; Bennett, Gary J.; Padi, Satyanarayana S.V.; Zhang, Ji; Coderre, Terence J.

    2015-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either ?2-adrenergic (?2A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post-ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5–10 fold leftward when combined with non-analgesic doses of ?2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of ?2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. Perspective This article presents the synergistic anti-allodynic effects of combinations of ?2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas. PMID:23273834

  13. Lysine and Arginine Reduce the Effects of Cerebral Ischemic Insults and Inhibit Glutamate-Induced Neuronal Activity in Rats

    PubMed Central

    Kondoh, Takashi; Kameishi, Makiko; Mallick, Hruda Nanda; Ono, Taketoshi; Torii, Kunio

    2010-01-01

    Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0?g/kg), arginine (0.6?g/kg), or their combined administration (0.6?g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6?g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects. PMID:20589237

  14. CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

    PubMed Central

    Necká?, Jan; Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Seidman, J. G.; Seidman, Christine; Kazdová, Ludmila; Klevstig, Martina; Novák, František; Vecka, Marek; Papoušek, František; Houšt?k, Josef; Drahota, Zden?k; Kurtz, Theodore W.; Kolá?, František

    2012-01-01

    CD36 fatty acid translocase plays a key role in supplying heart with its major energy substrate, long-chain fatty acids (FA). Previously, we found that the spontaneously hypertensive rat (SHR) harbors a deletion variant of Cd36 gene that results in reduced transport of long-chain FA into cardiomyocytes and predisposes the SHR to cardiac hypertrophy. In the current study, we analyzed the effects of mutant Cd36 on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in adult SHR-Cd36 transgenic rats with wild-type Cd36 compared with age-matched SHR controls. Using an open-chest model of coronary artery occlusion, we found that SHR-Cd36 transgenic rats showed profound arrhythmogenesis resulting in significantly increased duration of tachyarrhythmias (207 ± 48 s vs. 55 ± 21 s, P < 0.05), total number of premature ventricular complexes (2,623 ± 517 vs. 849 ± 250, P < 0.05) and arrhythmia score (3.86 ± 0.18 vs. 3.13 ± 0.13, P < 0.001). On the other hand, transgenic SHR compared with SHR controls showed significantly reduced infarct size (52.6 ± 4.3% vs. 72.4 ± 2.9% of area at risk, P < 0.001). Similar differences were observed in isolated perfused hearts, and the increased susceptibility of transgenic SHR to arrhythmias was abolished by reserpine, suggesting the involvement of catecholamines. To further search for possible molecular mechanisms of altered ischemic tolerance, we compared gene expression profiles in left ventricles dissected from 6-wk-old transgenic SHR vs. age-matched controls using Illumina-based sequencing. Circadian rhythms and oxidative phosphorylation were identified as the top KEGG pathways, while circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling were the top IPA canonical pathways potentially important for Cd36-mediated effects on ischemic tolerance. It can be concluded that transgenic expression of Cd36 plays an important role in modulating the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size induced by coronary artery occlusion. The proarrhythmic effect of Cd36 transgene appears to be dependent on adrenergic stimulation. PMID:22128087

  15. Posttreatment with high-dose albumin reduces histopathological damage and improves neurological deficit following fluid percussion brain injury in rats.

    PubMed

    Belayev, L; Alonso, O F; Huh, P W; Zhao, W; Busto, R; Ginsberg, M D

    1999-06-01

    We have recently shown that high-dose human serum albumin (HSA) therapy confers marked histological protection in experimental middle cerebral artery occlusion. Thus, the purpose of this study was to determine whether treatment with high-dose HSA would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, and 30% oxygen and received right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm). Cranial and rectal temperatures were monitored throughout the experiment and held at normothermic levels (36.5-37.5 degrees C) by a warming lamp above the animal's head. The agent (25% human serum albumin, HSA) or vehicle (sodium chloride 0.9%) was administered i.v. (1% of body weight) 15 min after trauma. Behavioral function was evaluated in all rats before and after TBI (at 2 h, 24 h, 48 h, 72 h, and 7 days). Neurological function was graded on a scale of 0-12 (normal score = 0; maximal score = 12). Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas in the superficial, middle and deep layers of cortex and in the underlying fimbria were measured. HSA significantly improved the neurological score compared to saline at 24 h, 72 h, and 7 days after TBI (6.0 +/- 0.6 [albumin] versus 8.4 +/- 0.5 [saline]; 3.6 +/- 0.7 versus 6.8 +/- 1.0; and 2.6 +/- 0.6 versus 5.7 +/- 0.8, respectively; p < 0.05). HSA therapy also significantly reduced total contusion area (0.89 +/- 0.2 versus 1.82 +/- 0.3 mm2; p = 0.02). Our findings document that high-concentration albumin therapy instituted 15 min after trauma significantly improves the neurological score and reduces histological damage. We believe that this pharmacological agent may have promising potential for the clinical treatment of brain injury. PMID:10391362

  16. Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye.

    PubMed

    Katagiri, A; Thompson, R; Rahman, M; Okamoto, K; Bereiter, D A

    2015-04-01

    Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil (MO), a transient receptor potential ankyrin (TRPA1) agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. MO (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of MO (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. MO caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by MO. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE. PMID:25639234

  17. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. An oral dose of calcium montmorillonite clay (i.e. NovaSil, NS) was able to reduce aflatoxin exposure in a Ghanaian population at risk. In vitro...

  18. Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats

    Microsoft Academic Search

    Laura Mattioli; Marina Perfumi

    2007-01-01

    Rhodiola rosea l. is one of the most popular adaptogen and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system. Exposure to both physical and psychological stress reduces feeding in rodents. The aim of this work was thus to determine

  19. STW 5 (Iberogast ®) reduces afferent sensitivity in the rat small intestine

    Microsoft Academic Search

    M. H. Müller; C.-Y. Liu; J. Glatzle; D. Weiser; O. Kelber; P. Enck; D. Grundy; M. E. Kreis

    2006-01-01

    IntroductionA limited number of drugs are available for the treatment of functional dyspepsia and irritable bowel syndrome. The efficacy of STW 5 (Iberogast®) was previously shown in clinical trials. Since visceral hypersensitivity seems to be the prime pathomechanism of functional gastro-intestinal disorders, the aim of this study was to explore whether STW 5 reduces intestinal afferent sensitivity in the upper

  20. Simvastatin reduces fetal testosterone production and permanently alters reproductive tract development in the male rat

    EPA Science Inventory

    Androgen signaling by fetal Leydig cells is critical in the proper development of the male reproductive tract. As cholesterol is a precursor for hormone biosynthesis,inhibition of the cholesterol pathway during sex differentiation may reduce testosterone {T). We hypothesized tha...

  1. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model

    E-print Network

    Hammock, Bruce D.

    allodynia in a rat model of inflammatory pain Bora Inceoglu a , Steven L. Jinks b , Kara R. Schmelzer and that sEH inhibitors effectively attenuate thermal hyperalgesia and mechanical allodynia in rats treated

  2. Inferring the use of forelimb suspensory locomotion by extinct primate species via shape exploration of the ulna.

    PubMed

    Rein, Thomas R; Harvati, Katerina; Harrison, Terry

    2015-01-01

    Uncovering links between skeletal morphology and locomotor behavior is an essential component of paleobiology because it allows researchers to infer the locomotor repertoire of extinct species based on preserved fossils. In this study, we explored ulnar shape in anthropoid primates using 3D geometric morphometrics to discover novel aspects of shape variation that correspond to observed differences in the relative amount of forelimb suspensory locomotion performed by species. The ultimate goal of this research was to construct an accurate predictive model that can be applied to infer the significance of these behaviors. We studied ulnar shape variation in extant species using principal component analysis. Species mainly clustered into phylogenetic groups along the first two principal components. Upon closer examination, the results showed that the position of species within each major clade corresponded closely with the proportion of forelimb suspensory locomotion that they have been observed to perform in nature. We used principal component regression to construct a predictive model for the proportion of these behaviors that would be expected to occur in the locomotor repertoire of anthropoid primates. We then applied this regression analysis to Pliopithecus vindobonensis, a stem catarrhine from the Miocene of central Europe, and found strong evidence that this species was adapted to perform a proportion of forelimb suspensory locomotion similar to that observed in the extant woolly monkey, Lagothrix lagothricha. PMID:25234204

  3. Female CGG Knock-In Mice Modeling the Fragile X Premutation are Impaired on a Skilled Forelimb Reaching Task

    PubMed Central

    Diep, Amanda A.; Hunsaker, Michael R.; Kwock, Richard; Kim, Kyoungmi; Willemsen, Rob; Berman, Robert F.

    2012-01-01

    The fragile X premutation is a tandem CGG trinucleotide repeat expansion in the Fragile X Mental Retardation 1 (FMR1) gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse has been developed that models the neuropathology and cognitive deficits reported in fragile X premutation carriers. Previous studies have demonstrated that CGG KI mice have spatiotemporal information processing deficits and impaired visuomotor function that worsen with increasing CGG repeat length. Since skilled forelimb reaching requires integration of information from the visual and motor systems, skilled reaching performance could identify potential visuomotor dysfunction in CGG KI mice. To characterize motor deficits associated with the fragile X premutation, 6 month old female CGG KI mice heterozygous for trinucleotide repeats ranging from 70–200 CGG in length were tested for their ability to learn a skilled forelimb reaching task. The results demonstrate that female CGG KI mice show deficits for learning a skilled forelimb reaching task compared to wildtype littermates, and that these deficits worsen with increasing CGG repeat lengths. PMID:22202169

  4. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging.

    PubMed

    Ménard, Caroline; Quirion, Rémi; Bouchard, Sylvain; Ferland, Guylaine; Gaudreau, Pierrette

    2014-01-01

    The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats. PMID:24847259

  5. Tamoxifen, a Selective Estrogen Receptor Modulator, Reduces Ischemic Damage Caused by Middle Cerebral Artery Occlusion in the Ovariectomized Female Rat

    Microsoft Academic Search

    Shyamal H. Mehta; Krishnan M. Dhandapani; Liesl M. De Sevilla; R. Clinton Webb; Virendra B. Mahesh; Darrell W. Brann

    2003-01-01

    Previous work has demonstrated that physiological concentrations of 17?-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, can similarly protect the female rat brain against ischemic stroke damage. Adult female rats were bilaterally ovariectomized and implanted subcutaneously

  6. Lycopene supplementation reduces TNF-? via RAGE in the kidney of obese rats

    PubMed Central

    Pierine, D T; Navarro, M E L; Minatel, I O; Luvizotto, R A M; Nascimento, A F; Ferreira, A L A; Yeum, K-J; Corręa, C R

    2014-01-01

    Background: The kidney is a target organ for injuries caused by advanced glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is proinflammatory and appears to have a role in the pathogenesis of renal disease due to obesity. Objective: The aim was to verify the effect of obesity on renal damage and the effect of lycopene on these complications Design and Methods: Male Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high-fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene (HD+S+L) for a 6-week period. Results: The HD+S and HD+S+L animals demonstrated insulin resistance (OGTT glucose after 150?min; C: 117.6±3.9

  7. Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing behavior in rats

    Microsoft Academic Search

    S. Hashimoto; T. Inoue; T. Koyama

    1996-01-01

    Conditioned fear stress (CFS)-induced freezing behavior has been proposed as an animal model of anxiety. In the present study, freezing was used to determine the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs), which are reported to be clinically effective in anxiety disorders. The duration of freezing behavior was reduced by acute treatment with the SSRIs citalopram (1–10 mg\\/kg) and

  8. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Hřydal, MA; Střlen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wislřff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  9. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    SciTech Connect

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A., E-mail: lucille.a.lange@us.army.mil

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of ?-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 ?g/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ? Soman (GD) produced seizure activity resulting in neuropathology in rats. ? Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ? CED/DZP showed superior anticonvulsant and neuroprotective capacity. ? Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ? PHY attenuated GD-induced seizure development, but not seizure duration.

  10. Flaxseed oil and ?-lipoic acid combination reduces atherosclerosis risk factors in rats fed a high-fat diet

    PubMed Central

    2012-01-01

    Background Atherosclerosis is a major manifestation of the pathophysiology underlying cardiovascular disease. Flaxseed oil (FO) and ?-lipoic acid (LA) have been reported to exert potential benefit to cardiovascular system. This study tried to assess the effect of supplement of FO and LA combination on the atherosclerosis risk factors in rats fed a high-fat diet. Methods LA was dissolved in flaxseed oil to a final concentration of 8 g/kg (FO+LA) when used. The rodent diet contained 20% fat. One-fifth of the fat was soybean oil and the others were lard (HFD group), or 75% lard and 25% FO+LA (L-FO+LA group), or 50% lard and 50% FO+LA (M-FO+LA group), or FO+LA (H-FO+LA group). Animals were fed for 10 weeks and then killed for blood collection. Results Supplement of FO and LA combination significantly enhanced plasma antioxidant defense capacities, as evaluated by the marked increase in the activities of SOD, CAT and GPx as well as the level of GSH, and the significant reduction in lipid peroxidation. Simultaneous intake of FO and LA also reduced plasma TG, TC and LDL-C contents and elevated the ratio of HDL-C/LDL-C. Besides, in parallel with the increase of FO and LA combination, plasma IL-6 and CRP levels were remarkably reduced. Conclusion Supplement of FO and LA combination may contribute to prevent atherogenesis by improving plasma oxidative stress, lipid profile and inflammation. PMID:23113997

  11. Different Modulation of Common Motor Information in Rat Primary and Secondary Motor Cortices

    PubMed Central

    Saiki, Akiko; Kimura, Rie; Samura, Toshikazu; Fujiwara-Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

    2014-01-01

    Rodents have primary and secondary motor cortices that are involved in the execution of voluntary movements via their direct and parallel projections to the spinal cord. However, it is unclear whether the rodent secondary motor cortex has any motor function distinct from the primary motor cortex to properly control voluntary movements. In the present study, we quantitatively examined neuronal activity in the caudal forelimb area (CFA) of the primary motor cortex and rostral forelimb area (RFA) of the secondary motor cortex in head-fixed rats performing forelimb movements (pushing, holding, and pulling a lever). We found virtually no major differences between CFA and RFA neurons, regardless of neuron subtypes, not only in their basal spiking properties but also in the time-course, amplitude, and direction preference of their functional activation for simple forelimb movements. However, the RFA neurons, as compared with the CFA neurons, showed obviously a greater susceptibility of their functional activation to an alteration in a behavioral situation, a 'rewarding' response that leads to reward or a 'consummatory' response that follows reward water, which might be accompanied by some internal adaptations without affecting the motor outputs. Our results suggest that, although the CFA and RFA neurons commonly process fundamental motor information to properly control forelimb movements, the RFA neurons may be functionally differentiated to integrate motor information with internal state information for an adaptation to goal-directed behaviors. PMID:24893154

  12. CHRONIC EXPOSURE TO DI(2-ETHYLHEXYL) PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN THE MALE RAT

    EPA Science Inventory

    DEHP, dibutyl (DBP)-, and benzyl butyl (BBP)- phthalate are plasticizers that cause adverse developmental reproductive effects in laboratory animals. They alter sexual differentiation in the rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels, which in ...

  13. PHTHALATE ESTER-INDUCED GUBERNACULAR LIGAMENT LESIONS ARE ASSOCIATED WITH REDUCED INSL3 GENE EXPRESSION IN THE FETAL RAT TESTIS DURING SEXUAL DIFFERENTIATION

    EPA Science Inventory

    Phthalate ester-induced gubernacular ligament lesions are associated with reduced Insl3 gene expression in the fetal rat testis during sexual differentiation. Vickie S Wilson, Christy Lambright, Johnathan Furr, Joseph Ostby, Carmen Wood, Gary Held, L.Earl Gray Jr. U.S. EPA,...

  14. Early postnatal alcohol exposure reduced the size of vibrissal barrel field in rat somatosensory cortex (SI) but did not disrupt barrel field organization

    Microsoft Academic Search

    Akinniran Oladehin; Cecilia P. Margret; Susan E. Maier; Cheng X. Li; Taha A. Jan; Tyson D. Chappell; Robert S. Waters

    2007-01-01

    Prenatal alcohol exposure (PAE) has been shown to alter the somatosensory cortex in both human and animal studies. In rodents, PAE reduced the size, but not the pattern of the posteromedial barrel subfield (PMBSF) associated with the representation of the whiskers, in newborn, juvenile, and adult rats. However, the PMBSF is not present at birth, but rather first appears in

  15. Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

    PubMed Central

    2012-01-01

    Background Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA)-induced monoarthritis (MA). In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. Results Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker) or the glia fibrillary acidic protein (GFAP, an astrocytic marker). These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs) ?2/?-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC ?2/?-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC ?2/?-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p.) gabapentin injections (100?mg/kg, once daily for 4?days with the first injection 60?min before intra-articular CFA) suppressed the activation of spinal microglia, downregulated spinal VGCC ?2/?-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. Conclusions Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia activation induced by joint inflammation. We also show that the VGCC ?2/?-1 subunits might be involved in these events. PMID:22647647

  16. Caveolar disruption causes contraction of rat femoral arteries via reduced basal NO release and subsequent closure of BKCa channels

    PubMed Central

    Al-Brakati, AY; Kamishima, T; Dart, C

    2015-01-01

    Background and Purpose. Caveolae act as signalling hubs in endothelial and smooth muscle cells. Caveolar disruption by the membrane cholesterol depleting agent methyl-?-cyclodextrin (M-?-CD) has various functional effects on arteries including (i) impairment of endothelium-dependent relaxation, and (ii) alteration of smooth muscle cell (SMC) contraction independently of the endothelium. The aim of this study was to explore the effects of M-?-CD on rat femoral arteries. Methods. Isometric force was measured in rat femoral arteries stimulated to contract with a solution containing 20 mM K+ and 200 nM Bay K 8644 (20 K/Bay K) or with one containing 80 mM K+(80 K). Results. Incubation of arteries with M-?-CD (5 mM, 60 min) increased force in response to 20 K/Bay K but not that induced by 80 K. Application of cholesterol saturated M-?-CD (Ch-MCD, 5 mM, 50 min) reversed the effects of M-?-CD. After mechanical removal of endothelial cells M-?-CD caused only a small enhancement of contractions to 20 K/Bay K. This result suggests M-?-CD acts via altering release of an endothelial-derived vasodilator or vasoconstrictor. When nitric oxide synthase was blocked by pre-incubation of arteries with L-NAME (250 µM) the contraction of arteries to 20 K/Bay K was enhanced, and this effect was abolished by pre-treatment with M-?-CD. This suggests M-?-CD is inhibiting endothelial NO release. Inhibition of large conductance voltage- and Ca2+-activated (BKCa) channels with 2 mM TEA+ or 100 nM Iberiotoxin (IbTX) enhanced 20 K/Bay K contractions. L-NAME attenuated the contractile effect of IbTX, as did endothelial removal. Conclusions. Our results suggest caveolar disruption results in decreased release of endothelial-derived nitric oxide in rat femoral artery, resulting in a reduced contribution of BKCa channels to the smooth muscle cell membrane potential, causing depolarisation and contraction. PMID:26038721

  17. A single trial of transcutaneous electrical nerve stimulation reduces chronic neuropathic pain following median nerve injury in rats.

    PubMed

    Cho, Hwi-Young; Suh, Hye Rim; Han, Hee Chul

    2014-01-01

    Neuropathic pain is a devastating chronic condition and is often induced in the upper limb following nerve injury or damage. Various drugs or surgical methods have been used to manage neuropathic pain; however, these are frequently accompanied by undesirable side effects. Transcutaneous electrical nerve stimulation (TENS) is a safe and non-invasive intervention that has been used to alleviate different types of pain in the clinic, but it is unclear whether TENS can improve chronic neuropathic pain in the upper limb. Thus, the aim of this study was to investigate the effects of a single trial of TENS on chronic neuropathic pain following median nerve injury. Male rats weighing 200-250 g received median nerve-ligation of the right forearm, while the control group received only skin-incision without nerve-ligation. Neuropathic pain-behaviors, including mechanical, cold, and thermal allodynia, were measured for 4 weeks. After the development of chronic neuropathic pain, TENS (100 Hz, 200 µs, sub-motor threshold) or placebo-TENS (sham stimulation) was applied for 20 min to the ipsilateral or contralateral side. Neuropathic pain behavior was assessed before and after intervention. Median nerve-ligation significantly induced and maintained neuropathic pain in the ipsilateral side. TENS application to the ipsilateral side effectively attenuated the three forms of chronic neuropathic pain in the ipsilateral side compared to sham-treated rats (peripheral and central effects), while TENS application to contralateral side only reduced mechanical allodynia in the ipsilateral side (central effect). Our findings demonstrate that TENS can alleviate chronic neuropathic pain following median nerve injury. PMID:24646955

  18. Intrathecal Administration of Mesenchymal Stem Cells Reduces the Reactive Oxygen Species and Pain Behavior in Neuropathic Rats

    PubMed Central

    Zhang, En Ji; Ko, Young Kwon

    2014-01-01

    Background Neuropathic pain induced by spinal or peripheral nerve injury is very resistant to common pain killers, nerve block, and other pain management approaches. Recently, several studies using stem cells suggested a new way to control the neuropatic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate whether intrathecal rat mesenchymal stem cells (rMSCs) were able to decrease pain behavior, as well as the relationship between rMSCs and reactive oxygen species (ROS). Methods Neuropathic pain of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats (n = 10 in each group). Mechanical sensitivity was assessed using Von Frey filaments at 3, 7, 10, 12, 14, 17, and 24 days post-ligation. rMSCs (10 µl, 1 × 105) or phosphate buffer saline (PBS, 10 µl) was injected intrathecally at 7 days post-ligation. Dihydroethidium (DHE), an oxidative fluorescent dye, was used to detect ROS at 24 days post-ligation. Results Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw after 3 days post-ligation. ROS expression was increased significantly (P < 0.05) in spinal dorsal horn of L5. Intrathecal rMSCs significantly (P < 0.01) alleviated the allodynia at 10 days after intrathecal injection (17 days post-ligation). Intrathecal rMSCs administration significantly (P < 0.05) reduced ROS expression in the spinal dorsal horn. Conclusions These results suggest that rMSCs may modulate neuropathic pain generation through ROS expression after spinal nerve ligation. PMID:25031809

  19. Immunotoxicity of nucleic acid reduced BioProtein--a bacterial derived single cell protein--in Wistar rats.

    PubMed

    Mřlck, Anne-Marie; Poulsen, Morten; Christensen, Hanne Risager; Lauridsen, Sřren Tindgard; Madsen, Charlotte

    2002-06-01

    BioProtein is a single cell protein produced by a mixed methanotrophic and heterotrophic bacteria culture using natural gas as energy source, which has been approved for animal feed. BioProtein contains a large amount of nucleic acids making the product less suitable for human consumption, therefore, a nucleic acid reduced variant (NABP) has been developed by the manufacturer. The purpose of the present study was to establish the safety of NABP in a subchronic toxicity rat study. Groups of 10 male and 10 female Wistar rats were fed diets containing 0, 6, 12 or 24% NABP for 13 weeks. Feeding NABP induced a humoral immune response and proliferation of phagocytic cell lines, mainly macrophages. The humoral response involved induction of NABP specific IgM and IgG. The proliferation of phagocytic cells involved increase of the white blood cell count of all dosed female groups. Males showed the same tendency, although, not statistically significant (P=0.09). The subsets of cells identified as neutrophils and eosinophils were increased and lymphocytes decreased. The histopathological examination revealed histiocytosis and accumulation of foamy macrophages in the mesenteric lymph nodes, hyperplasia of Kupffer cells in the liver, increased granulopoiesis in spleen and bone marrow, and infiltration of lamina propria of the large intestine with eosinophilic granulocytes. The most consistent and pronounced changes were observed in the highest dose group, but even at the lowest dose level some of the changes were present. Accordingly, a no-observed-effect level could not be established based on this study. PMID:12007858

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

    PubMed

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

    2014-08-01

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

  1. PRENATAL ETHANOL EXPOSURE INCREASES ETHANOL INTAKE AND REDUCES C-FOS EXPRESSION IN INFRALIMBIC CORTEX OF ADOLESCENT RATS

    PubMed Central

    Fabio, Maria Carolina; March, Samanta M.; Molina, Juan Carlos; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2013-01-01

    Prenatal ethanol exposure significantly increases later predisposition for alcohol intake, but the mechanisms associated with this phenomenon remain hypothetical. This study analyzed (Exp. 1) ethanol intake in adolescent inbred WKAH/Hok Wistar rats prenatally exposed to ethanol (2.0 g/kg) or vehicle, on gestational days 17–20. Subsequent Experiments (2, 3 and 4) tested several variables likely to underlie the effect of gestational ethanol on adolescent ethanol preference, including ethanol-induced locomotor activation (LMA), ethanol-induced emission of ultrasonic vocalizations (USVs) after exposure to a rough exteroceptive stimulus, and induction of the immediate early gene C-fos in brain areas associated with processing of reward stimuli and with the retrieval and extinction of associative learning. Prenatal ethanol induced a two-fold increase in ethanol intake. Adolescents exhibited significant ethanol-induced LMA, emitted more aversive than appetitive USVs, and postnatal ethanol administration significantly exacerbated the emission of USVs. These effects, however, were not affected by prenatal ethanol. Adolescents prenatally exposed to ethanol as fetuses exhibited reduced neural activity in infralimbic cortex (but not in prelimbic cortex or nucleus accumbens core or shell), an area that has been implicated in the extinction of drug-mediated associative memories. Ethanol metabolism was not affected by prenatal ethanol. Late gestational exposure to ethanol significantly heightened drinking in the adolescent offspring of an inbred rat strain. Ethanol-induced LMA and USVs were not associated with differential ethanol intake due to prenatal ethanol exposure. Prenatal ethanol, however, altered basal neural activity in the infralimbic prefrontal cortex. Future studies should analyze the functionality of medial prefrontal cortex after prenatal ethanol and its potential association with predisposition for heightened ethanol intake. PMID:23266368

  2. Carbamoylation of Glutathione ReducĂ­aseand Changes in Cellular and Chromosome Morphology in a Rat Cell Line Resistant to Nitrogen Mustards but Collaterally Sensitive to Nitrosoureas1

    Microsoft Academic Search

    Kenneth D. Tew; Gregg Kyle; Alfred Johnson; Ann L. Wang

    A Walker 256 rat carcinoma cell line (WR) with acquired resistance to nitrogen mustards has been found to lack cross- resistance to nitrosoureas. Although total cellular glutathione pools were similar in the parent (WS) and resistant cell lines (WS, 2.5 x 10~6;WR, 2.0 x 10~6mol\\/mg protein), glutathione reduc- tase activity was 3.98 in WR compared to 8.67 nmol reduced nicotinamide

  3. Reduced expression of arrestin beta 2 by graft monocytes during acute rejection of rat kidneys.

    PubMed

    Zakrzewicz, Anna; Krasteva, Gabriela; Wilhelm, Jochen; Dietrich, Hartmut; Wilker, Sigrid; Padberg, Winfried; Wygrecka, Malgorzata; Grau, Veronika

    2011-07-01

    During acute rejection, numerous pro-inflammatory and cytotoxic monocytes accumulate in the vasculature of experimental renal allografts. Arrestins (ARRBs) are cellular regulators of inflammation, but nothing is known about their expression during rejection. Intravascular mononuclear graft leukocytes were isolated 4 days after kidney transplantation. ARRB1 and ARRB2 mRNA expression was reduced in blood leukocytes from allografts undergoing acute rejection, whereas on the protein level only ARRB2 was changed. Flow cytometry and confocal microscopy revealed ARRB1 and ARRB2 expression by monocytes and T cells, with a selective decrease in ARRB2 expression in monocytes during acute rejection. I-?B directly interacted with ARRB2 and the levels of both proteins strongly correlated. Concomitantly, the mRNA expression of NF-?B targeted genes increased. Our results suggest that activation of blood monocytes in renal isografts is dampened by high ARRB2 levels. During acute rejection, ARRB2 levels are reduced and classical monocyte activation is enabled via NF-?B activation. PMID:21193245

  4. Isoflurane reduces hypoxia/reoxygenation-induced apoptosis and mitochondrial permeability transition in rat primary cultured cardiocytes

    PubMed Central

    2014-01-01

    Background The volatile anesthetic isoflurane protects the heart from hypoxia/reperfusion (H/R) injury. However, it is still incompletely understood whether isoflurane exerts its protective role through preventing mitochondrial permeability transition pore (MPTP) opening. Methods Primary cultured cardiocytes were exposed to H/R in the absence or presence of isoflurane. Cell cytotoxicity and apoptosis were detected by MTT assay and TUNEL staining, respectively. MPTP function was monitored by confocal imaging after reoxygenation. ROS production and activation of caspase-3 were determined by fluorescent reader and western blot, respectively. Results As compared to the control group, H/R led to significant cell cytotoxicity and apoptosis, while application of isoflurane markedly reversed the effects. Furthermore, isoflurane significantly inhibits the formation of H/R-induced excess ROS production. Finally, isoflurane attenuated the onset of mitochondrial permeability transition pore (MPTP) occurred during hypoxia/reoxygenation, and in turn inhibited activation of caspase-3. Conclusions These data indicate that isoflurane has a protective effect on cardiocytes exposed to H/R by reducing excess ROS production, blocking open of MPTP and further reducing apoptosis. PMID:24612850

  5. Low-dose nicotine self-administration is reduced in adult male rats naďve to high doses of nicotine: implications for nicotine product standards.

    PubMed

    Smith, Tracy T; Schassburger, Rachel L; Buffalari, Deanne M; Sved, Alan F; Donny, Eric C

    2014-10-01

    Product standards that greatly reduce the content of nicotine within cigarettes may result in improved public health. The study presented here used an animal model to investigate whether individuals who start smoking after implementation of regulation may be affected differently from current smokers who form the basis of most clinical studies. One group of adult male rats (n = 14/group) acquired nicotine self-administration at a high nicotine dose (60 ?g/kg/infusion) before experiencing a reduction to one to three low doses of nicotine (3.75, 7.5, or 15 ?g/kg/infusion) or vehicle. Their self-administration behavior at the low doses was compared with a group of adult male rats given the opportunity to acquire nicotine self-administration at one of the same low doses or vehicle (n = 7-14/group). Second, the self-administration behavior of the acquisition group of rats was compared with their own self-administration behavior after experience self-administering a high dose of nicotine. A cocktail of non-nicotine cigarette smoke constituents was included in the vehicle for all rats across all phases of the study. Rats with a history of self-administering a high dose of nicotine had a higher rate of self-administration across the low doses than rats with no history. In addition, the number of earned infusions increased after rats experienced self-administration of a higher dose of nicotine. These data show that low-dose nicotine self-administration is higher after a dose reduction than during acquisition. If a nicotine reduction policy were implemented, then this policy may be especially effective at reducing acquisition of smoking. PMID:24999867

  6. Sensorimotor restriction affects complex movement topography and reachable space in the rat motor cortex

    PubMed Central

    Budri, Mirco; Lodi, Enrico; Franchi, Gianfranco

    2014-01-01

    Long-duration intracortical microstimulation (ICMS) studies with 500 ms of current pulses suggest that the forelimb area of the motor cortex is organized into several spatially distinct functional zones that organize movements into complex sequences. Here we studied how sensorimotor restriction modifies the extent of functional zones, complex movements, and reachable space representation in the rat forelimb M1. Sensorimotor restriction was achieved by means of whole-forelimb casting of 30 days duration. Long-duration ICMS was carried out 12 h and 14 days after cast removal. Evoked movements were measured using a high-resolution 3D optical system. Long-term cast caused: (i) a reduction in the number of sites where complex forelimb movement could be evoked; (ii) a shrinkage of functional zones but no change in their center of gravity; (iii) a reduction in movement with proximal/distal coactivation; (iv) a reduction in maximal velocity, trajectory and vector length of movement, but no changes in latency or duration; (v) a large restriction of reachable space. Fourteen days of forelimb freedom after casting caused: (i) a recovery of the number of sites where complex forelimb movement could be evoked; (ii) a recovery of functional zone extent and movement with proximal/distal coactivation; (iii) an increase in movement kinematics, but only partial restoration of control rat values; (iv) a slight increase in reachability parameters, but these remained far below baseline values. We pose the hypothesis that specific aspects of complex movement may be stored within parallel motor cortex re-entrant systems. PMID:25565987

  7. Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism.

    PubMed

    Underdown, Nichola J; Hiley, C Robin; Ford, William R

    2005-11-01

    Although the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide share a similar pharmacology, 2-AG reportedly limits myocardial ischaemia-reperfusion injury whereas anandamide does not. We therefore investigated whether or not anandamide reduces infarct size and which, if any, of the known cannabinoid-signalling pathways are involved. Rat isolated perfused hearts were subjected to global, no-flow ischaemia (30 min) and reperfusion (1 h). Agonists were present from 5 min before ischaemia until the end of reperfusion. Antagonists, where used, were present throughout the protocol. Recovery of left ventricular developed pressure and coronary flow was incomplete in control hearts and not significantly affected by any drug treatment. In vehicle-treated hearts, 26+/-3% (n=13) of the left ventricle was infarcted at the end of reperfusion. Infarction of the left ventricle was significantly reduced after 1 microM anandamide (10+/-1%, n=7) or 1 microM methanandamide (12+/-4%, n=6) but not 1 microM HU210. Neither ACPA (1 microM; CB1 receptor agonist) nor JWH133 (1 microM; CB2 receptor agonist), individually or combined significantly affected infarct size. Anandamide (1 microM) did not reduce infarct size in the presence of the CB1 receptor antagonist rimonabant (SR141716A, 1 microM) or the CB2 receptor antagonist, SR144528 (1 microM). Despite sensitivity to CB1 and CB2 receptor antagonists, the infarct-limiting action of anandamide was not mimicked by agonists selective for CB1 or CB2 receptors suggesting the involvement of a novel cannabinoid site of action. PMID:16158067

  8. Sustained sensorimotor impairments after endothelin-1 induced focal cerebral ischemia (stroke) in aged rats.

    PubMed

    Soleman, Sara; Yip, Ping; Leasure, J Leigh; Moon, Lawrence

    2010-03-01

    Despite recent advances, stroke remains a leading cause of neurological disability with the vast majority of victims being the elderly, who exhibit more severe neurological deficits and a reduced capacity to recover from these disabilities in comparison to young stroke survivors. The objective of the present study was to develop a model of focal ischemic stroke in aged rats using endothelin-1 (ET-1) to produce low mortality rates as well as reliable, robust sensorimotor deficits that resemble functional impairments associated with stroke in humans. Here, we studied the functional and histological outcome following unilateral ET-1 infusions into the sensorimotor cortex of aged rats (20-23 months old). This procedure resulted in low mortality rates (13.3%) and no loss in body weight one week following surgery. Functional assessment was performed using a number of reliable behavioural tests: staircase test (fine motor function), horizontal ladder (skilled locomotion), bilateral tactile stimulation test (somatosensory function) and cylinder test (postural weight support). Following ET-1 induced stroke, all tests demonstrated large and sustained sensorimotor deficits in both forelimb and hindlimb function that failed to improve over the 28-day testing period. In addition, histological assessment revealed a substantial loss of retrogradely labelled corticospinal neurons in the ipsilesional hemisphere following stroke. Our results establish a model for the use of aged rats in future preclinical studies, which will enhance assessment of the long-term benefit of potential neural repair and regenerative strategies. PMID:19913535

  9. Sustained sensorimotor impairments after endothelin-1 induced focal cerebral ischemia (stroke) in aged rats

    PubMed Central

    Soleman, Sara; Yip, Ping; Leasure, J. Leigh; Moon, Lawrence

    2010-01-01

    Despite recent advances, stroke remains a leading cause of neurological disability with the vast majority of victims being the elderly, who exhibit more severe neurological deficits and a reduced capacity to recover from these disabilities in comparison to young stroke survivors. The objective of the present study was to develop a model of focal ischemic stroke in aged rats using endothelin-1 (ET-1) to produce low mortality rates as well as reliable, robust sensorimotor deficits that resemble functional impairments associated with stroke in humans. Here, we studied the functional and histological outcome following unilateral ET-1 infusions into the sensorimotor cortex of aged rats (20–23 months old). This procedure resulted in low mortality rates (13.3%) and no loss in body weight one week following surgery. Functional assessment was performed using a number of reliable behavioural tests: staircase test (fine motor function), horizontal ladder (skilled locomotion), bilateral tactile stimulation test (somatosensory function) and cylinder test (postural weight support). Following ET-1 induced stroke, all tests demonstrated large and sustained sensorimotor deficits in both forelimb and hindlimb function that failed to improve over the 28-day testing period. In addition, histological assessment revealed a substantial loss of retrogradely labelled corticospinal neurons in the ipsilesional hemisphere following stroke. Our results establish a model for the use of aged rats in future preclinical studies, which will enhance assessment of the long-term benefit of potential neural repair and regenerative strategies. PMID:19913535

  10. GM1 reduces injury-induced metabolic deficits and degeneration in the rat optic nerve.

    PubMed

    Yoles, E; Zalish, M; Lavie, V; Duvdevani, R; Ben-Bassat, S; Schwartz, M

    1992-12-01

    This study demonstrates the earliest reported effects of GM1 treatment on crush-injured axons of the mammalian optic nerve. GM1, administered intraperitoneally immediately after injury, was found to reduce the injury-induced metabolic deficit in nerve activity within 2 hr of injury, as measured by changes in the nicotine-amine adenine dinucleotide redox state. After 4 wk, transmission electron microscopy 1 mm distal to the site of injury revealed a sevenfold increase in axonal survival in GM1-treated compared to untreated injured nerves. These results emphasize the beneficial effect of GM1 on injured optic nerves as well as the correlation between immediate and long-term consequences of the injury. Thus, these results have implications for treating damaged optic nerves. PMID:1464504

  11. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and Renin Angiotensin system.

    PubMed

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-? agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA. PMID:25951330

  12. Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System

    PubMed Central

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-? agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA. PMID:25951330

  13. Central opioid receptor subtype antagonists differentially reduce intake of saccharin and maltose dextrin solutions in rats.

    PubMed

    Beczkowska, I W; Koch, J E; Bostock, M E; Leibowitz, S F; Bodnar, R J

    1993-08-01

    Opioid modulation of ingestion includes general opioid antagonism of deprivation-induced water intake and intake of sucrose and saccharin solutions. Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occurred through the mu2 receptor and that opioid effects upon sucrose intake occurred through kappa and mu2 receptors. The present study compared the effects of intracerebroventricular administration of opioid receptor subtype antagonists upon intakes of a saccharin solution and a maltose dextrin (MD) solution to determine which receptor subtypes were involved in modulation of ingestion of different preferred tastants. Significant reductions in saccharin intake (1 h) occurred following naltrexone (20-50 micrograms: 66%) and naltrindole (delta, 20 micrograms: 75%), whereas [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, delta 1, 40 micrograms: 45%) had transient (5 min) effects. Neither beta-funaltrexamine (B-FNA, mu), naloxonazine (mu1), nor nor-binaltorphamine (Nor-BNI, kappa) significantly altered saccharin intake. Significant reductions in MD intake (1 h) occurred following naltrexone (5-50 micrograms: 69%) and B-FNA (1-20 micrograms: 38%). MD intake was not reduced by naltrindole, DALCE, naloxonazine and Nor-BNI. Peak antagonist effects were delayed (20-25 min) to reflect interference with the maintenance, rather than the initiation of saccharin or MD intake. Comparisons of opioid antagonist effects across intake situations revealed that naltrexone had consistently low ID40 values for saccharin (29 nmol), MD (25 nmol), sucrose (6 nmol) and deprivation (38 nmol) intake. Despite its significant effects relative to naloxonazine, B-FNA had significantly higher ID40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu2 receptors may be mediating maintenance of intake rather than taste effects. Nor-BNI had low ID40 values for intake of sucrose (4 nmol), but not for saccharin (168 nmol), MD (153 nmol) and deprivation (176 nmol), suggesting that kappa receptors may mediate ingestion of sweet-tasting stimuli. That delta (naltrindole: ID40 = 60 nmol), but not delta 1 (DALCE: ID40 = 288 nmol) antagonists consistently reduce saccharin intake suggests a role for the delta 2 receptor subtype in the modulation of hedonic orosensory signals. PMID:8397050

  14. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes.

    PubMed

    Kim, Kyoung Soo; Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyun Ju; Yoo, Myung Chul; Yang, Hyung In; Kang, Ja Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho Yeon; Jeong, In Kyung

    2012-11-30

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long- Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve ?-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  15. Prenatal haloperidol reduces the number of active midbrain dopamine neurons in rat offspring.

    PubMed

    Zhang, J; Wang, L; Pitts, D K

    1996-01-01

    The dopamine (DA) receptor antagonist, haloperidol (HAL, 1.25 or 5 mg/kg), or vehicle, dimethyl sulfoxide (DMSO), was administered (SC) daily to pregnant Sprague-Dawley dams from gestational day (GD) 8 to GD 20. The average body weight of 2-week-old male offspring was significantly lower in all of the HAL-treated groups relative to controls. In extracellular electrophysiological studies, the male 2-week-old offspring from all HAL treatment groups were found to have significantly reduced average numbers of spontaneously active midbrain dopamine (DA)-containing neurons in both the substantia nigra (A9) and the ventral tegmental area (A10) relative to controls. In DA neurons classified as bursting neurons, HAL exposure (5 mg/kg) caused a significantly increased level of burst activity in A10 but not A9 DA neurons relative to controls. For both the A9 and A10 regions, the proportion of DA neurons classified as bursting or nonbursting was unaffected by HAL treatment. These results suggest that prenatal HAL exposure influences the development of midbrain DA neurons. PMID:8700043

  16. Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin, CaMK II and calmodulin and elevates calcineurin in lactational rats

    Microsoft Academic Search

    Jing Dong; Wanyang Liu; Yi Wang; Qi Xi; Jie Chen

    2010-01-01

    Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal neurogranin, calcium\\/calmodulin dependent protein kinase II (CaMKII), calmodulin (CaM) and calcineurin (CaN) are implicated in the brain impairment in lactational rat hippocampus following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats

  17. Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

    PubMed Central

    Kova?evi?, Tomislav; Skelin, Ivan; Minuzzi, Luciano; Rosa-Neto, Pedro; Diksic, Mirko

    2013-01-01

    Depression is a brain disorder and there is still only a partial understanding of its underlying pathophysiology. Antidepressant medications with a fast onset have not yet been developed. In addition to the monoaminergic systems, the brain glutaminergic system has been implicated in the etiology of depression. Animal studies of depression have gained importance because they permit a more invasive manipulation of the subjects than human studies. In the present study, we measured the densities of the brain regional metabotropic glutaminergic receptor 5 (mGluR5) in the Flinders Sensitive Line (FSL) rat model of depression and two groups of control rats, the Flinders Resistant Line (FRL) and Sprague Dawley (SPD), the parent strain for both the FSL and FRL rats. The FSL rats showed lower densities of mGluR5 in many brain regions compared to either the SPD and/or FRL rats. In addition, the densities in the FRL rats were larger than in the SPD rats, suggesting possible problems in using FRL rats as controls. The presented data suggest that mGluR5 is lower in animal models of depression which could be related to the cognitive and emotional dysfunctions in the FSL rat model of depression and could be relevant to a better understanding of depression in humans. PMID:22310150

  18. Stability of output effects from motor cortex to forelimb muscles in primates

    PubMed Central

    Griffin, D.M.; Hudson, H.M.; Belhaj-Saďf, A.; Cheney, P.D.

    2009-01-01

    Stimulus-triggered averaging (StTA) of electromyographic (EMG) activity is a form of intracortical microstimulation that enables documentation in awake animals of the sign, magnitude, latency and distribution of output effects from cortical and brainstem areas to motoneurons of different muscles. In this study, we show that the properties of effects in StTAs are stable and mostly independent of task conditions. StTAs of EMG activity from 24 forelimb muscles were collected from two male rhesus monkeys while they performed three tasks: 1) an isometric step tracking wrist task, 2) an isometric whole arm push-pull task and 3) a reach-to-grasp task. Layer V sites in primary motor cortex were identified and microstimuli were applied (15 ?A) at a low rate (15 Hz). Our results show that the sign of effects (facilitation or suppression) in StTAs of EMG activity are remarkably stable in the presence of joint angle position changes (96% stable), whole arm posture changes (97% stable) and across fundamentally different types of tasks such as arm push-pull versus reach-to-grasp (81% stable). Further, comparing effects across different phases of a task also yielded remarkable stability (range: 84% - 96%). At different shoulder, elbow and wrist angles, the magnitudes of effects in individual muscles were highly correlated. Our results demonstrate that M1 output effects obtained with StTA of EMG activity are highly stable across widely varying joint angles and motor tasks. This study further validates the use of StTA for mapping and other studies of cortical motor output. PMID:19211898

  19. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate.

    PubMed

    Dairam, Amichand; Fogel, Ronen; Daya, Santy; Limson, Janice L

    2008-05-14

    Research demonstrates that antioxidants and metal chelators may be of beneficial use in the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). This study investigated the antioxidant and metal-binding properties of curcumin, capsaicin, and S-allylcysteine, which are major components found in commonly used dietary spice ingredients turmeric, chilli, and garlic, respectively. The DPPH assay demonstrates that these compounds readily scavenge free radicals. These compounds significantly curtail iron- (Fe2+) and quinolinic acid (QA)-induced lipid peroxidation and potently scavenge the superoxide anion generated by 1 mM cyanide in rat brain homogenate. The ferrozine assay was used to measure the extent of Fe2+ chelation, and electrochemistry was employed to measure the Fe3+ binding activity of curcumin, capsaicin, and S-allylcysteine. Both assays demonstrate that these compounds bind Fe2+ and Fe3+ and prevent the redox cycling of iron, suggesting that this may be an additional method through which these agents reduce Fe2+-induced lipid peroxidation. This study demonstrates the antioxidant and metal-binding properties of these spice ingredients, and it is hereby postulate that these compounds have important implications in the prevention or treatment of neurodegenerative diseases such as AD. PMID:18422331

  20. ?-Hydroxy-?-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats.

    PubMed

    Hao, Yanlei; Jackson, Janna R; Wang, Yan; Edens, Neile; Pereira, Suzette L; Alway, Stephen E

    2011-09-01

    ?-Hydroxy-?-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P < 0.05) and soleus muscles (3.9% vs. 1.8%, P < 0.05). Although HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P < 0.05) in plantaris and soleus muscles, respectively. Cleaved caspase-3 was reduced by 12% and 9% (P < 0.05) in HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P < 0.05) in reloaded plantaris and soleus muscles, respectively, compared with vehicle-treated animals. Although, HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial-associated caspase signaling. PMID:21697520

  1. Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats

    Microsoft Academic Search

    Julie Borch; Ole Ladefoged; Ulla Hass; Anne Marie Vinggaard

    2004-01-01

    The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP with DEHA and DINP have led to the hypothesis that similarities in action may also exist. Pregnant Wistar rats were gavaged during gestation and

  2. Reduced red blood cell membrane damage in streptozotocin-induced diabetic rats supplemented with roselle (UKMR-2) calyx extract.

    PubMed

    Mohamed, J; Wen, H K; Idris, M H M; Zainalabidin, S; Budin, S B

    2014-05-01

    The aim of this study was to evaluate the effects of aqueous extract of roselle on the membrane composition of red blood cells. A total of 32 male Sprague-Dawley rats (230-250 g) were divided randomly into four groups. Diabetic rats were induced streptozotocin (45 mg kg(-1), i.v). The normal and diabetes groups were administrated with distilled water. The other normal and diabetes group were administrated with roselle aqueous extracts (100 mg kg(-1)). After 28 days, the blood was drawn by sinus orbital for biochemical tests including membrane total protein, cholesterol and phosphatidylcholine and morphology of red blood cells was carried out through light microscope. In diabetic rats, the result showed the weight of rat, membrane total protein and Phosphatidylcholine (PCh) were significantly lower (p<0.05), while blood glucose and membrane cholesterol showed significantly higher (p<0.05) than control rats. In diabetic rats demonstrated with roselle, the result showed no significant difference (p>0.05) in weight and blood glucose compared to diabetic rats. The membrane total protein and PCh were significantly higher (p<0.05) than diabetic rats, whereas membrane cholesterol was significantly lower (p<0.05) compared to diabetic rats. The observation red blood cells morphology that showed echinocytes, schistocytes and Heinz body in diabetic rats was caused by oxidative stress damage. The morphology of red blood cells in diabetic rats supplemented with roselle is normal. Aqueous extract of roselle showed potential protective effects on membrane composition of damaged red blood cells. PMID:26031001

  3. Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats*

    PubMed Central

    Brouwers, Olaf; Niessen, Petra M.; Ferreira, Isabel; Miyata, Toshio; Scheffer, Peter G.; Teerlink, Tom; Schrauwen, Patrick; Brownlee, Michael; Stehouwer, Coen D.; Schalkwijk, Casper G.

    2011-01-01

    The reactive advanced glycation end product (AGE) precursor methylglyoxal (MGO) and MGO-derived AGEs are associated with diabetic vascular complications and also with an increase in oxidative stress. Glyoxalase-I (GLO-I) transgenic rats were used to explore whether overexpression of this MGO detoxifying enzyme reduces levels of AGEs and oxidative stress in a rat model of diabetes. Rats were made diabetic with streptozotocin, and after 12 weeks, plasma and multiple tissues were isolated for analysis of AGEs, carbonyl stress, and oxidative stress. GLO-I activity was significantly elevated in multiple tissues of all transgenic rats compared with wild-type (WT) littermates. Streptozotocin treatment resulted in a 5-fold increase in blood glucose concentrations irrespective of GLO-I overexpression. Levels of MGO, glyoxal, 3-deoxyglucosone, AGEs, and oxidative stress markers nitrotyrosine, malondialdehyde, and F2-isoprostane were elevated in the diabetic WT rats. In diabetic GLO-I rats, glyoxal and MGO composite scores were significantly decreased by 81%, and plasma AGEs and oxidative stress markers scores were significantly decreased by ?50%. Hyperglycemia induced a decrease in protein levels of the mitochondrial oxidative phosphorylation complex in the gastrocnemius muscle, which was accompanied by an increase in the lipid peroxidation product 4-hydroxy-2-nonenal, and this was counteracted by GLO-I overexpression. This study shows for the first time in an in vivo model of diabetes that GLO-I overexpression reduces hyperglycemia-induced levels of carbonyl stress, AGEs, and oxidative stress. The reduction of oxidative stress by GLO-I overexpression directly demonstrates the link between glycation and oxidative stress. PMID:21056979

  4. Forelimb kinematics and motor patterns of the slider turtle (Trachemys scripta) during swimming and walking: shared and novel strategies for meeting locomotor demands of water and land.

    PubMed

    Rivera, Angela R V; Blob, Richard W

    2010-10-15

    Turtles use their limbs during both aquatic and terrestrial locomotion, but water and land impose dramatically different physical requirements. How must musculoskeletal function be adjusted to produce locomotion through such physically disparate habitats? We addressed this question by quantifying forelimb kinematics and muscle activity during aquatic and terrestrial locomotion in a generalized freshwater turtle, the red-eared slider (Trachemys scripta), using digital high-speed video and electromyography (EMG). Comparisons of our forelimb data to previously collected data from the slider hindlimb allow us to test whether limb muscles with similar functional roles show qualitatively similar modulations of activity across habitats. The different functional demands of water and air lead to a prediction that muscle activity for limb protractors (e.g. latissimus dorsi and deltoid for the forelimb) should be greater during swimming than during walking, and activity in retractors (e.g. coracobrachialis and pectoralis for the forelimb) should be greater during walking than during swimming. Differences between aquatic and terrestrial forelimb movements are reflected in temporal modulation of muscle activity bursts between environments, and in some cases the number of EMG bursts as well. Although patterns of modulation between water and land are similar between the fore- and hindlimb in T. scripta for propulsive phase muscles (retractors), we did not find support for the predicted pattern of intensity modulation, suggesting that the functional demands of the locomotor medium alone do not dictate differences in intensity of muscle activity across habitats. PMID:20889832

  5. Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of Chemerin and ChemR23 in the kidney of streptozotocin-induced diabetic rats.

    PubMed

    Hu, Wenchao; Yu, Qian; Zhang, Jie; Liu, Demin

    2012-08-01

    Chemerin is shown to be associated with inflammation which is involved in the pathogenesis of diabetic nephropathy. This study aims to determine whether rosiglitazone and pioglitazone ameliorate renal function through an effect on the expression of chemerin and ChemR23 in streptozotocin-induced diabetic rats. The rats were randomized to control, diabetic, rosiglitazone-, and pioglitazone-treated groups. The expression level of chemerin and ChemR23 in the renal tissues was significantly elevated in the diabetic group compared with the control group. Rosiglitazone inhibited the overexpression of chemerin and ChemR23, while pioglitazone inhibited the overexpression of ChemR23 in the kidney of diabetic rats. In addition, chemerin expression level was positively correlated with transforming growth factor-?1, connective tissue growth factor, tumor necrosis factor-?, and intracellular cell adhesion molecule-1 expression in diabetic rats. Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of chemerin and ChemR23 in diabetic rats. PMID:22350950

  6. Electro-acupuncture attenuates behavioral hyperalgesia and selectively reduces spinal fos protein expression in rats with persistent inflammation

    Microsoft Academic Search

    Lixing Lao; Grant Zhang; Feng Wei; Brian M. Berman; Ke Ren

    2001-01-01

    This study examined the effect of electro-acupuncture (EA) on persistent inflammatory hyperalgesia in a rat model. Inflammation and hyperalgesia were induced by injecting complete Freund's adjuvant (CFA) into one hindpaw of the rat. Hyperalgesia was determined by a decrease in paw withdrawal latencies (PWL) to a noxious thermal stimulus. EA was applied bilaterally at the acupuncture point Huantiao (G30) at

  7. Continuous perfusion with morphine of the orbitofrontal cortex reduces allodynia and hyperalgesia in a rat model for mononeuropathy

    Microsoft Academic Search

    Hassen A. Al Amin; Samir F. Atweh; Samah Abdel Baki; Suhayl J. Jabbur; Nayef E. Saadé

    2004-01-01

    Recent imaging reports demonstrate the activation of the orbitofrontal cortical (OFC) area during acute and chronic pain. The aim of this study was to compare the effects of chronic perfusion of this area with morphine on nociception in control rats and in rats subjected to mononeuropathy. Chronic perfusion of morphine, using miniosmotic pumps, produced significant and naloxone-reversible depression of tactile

  8. INADEQUATE COPPER INTAKE REDUCES SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) AND BONE STRENGTH IN GROWING RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effects of graded intakes of zinc (Zn) and copper (Cu) on serum insulin-like growth-factor-1 (IGF-1) concentration and bone quality in growing rats. Using a 3x4 factorial design, weanling, male Sprague Dawley rats were randomly assigned to 12 groups (n=7 per group) and were ...

  9. Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride concentrations in rats fed a high-cholesterol diet

    Microsoft Academic Search

    Taesun Park; Kyungshin Lee; Youngsook Um

    1998-01-01

    The effect of dietary taurine supplementation on plasma and hepatic lipid levels and phospholipid profiles were evaluated in rats fed a high-cholesterol diet. Three groups of male rats were fed one of the following diets for 5 weeks: control diet (CD, cholesterol-free diet); high cholesterol diet (HCD, CD + 1.5% cholesterol); or high cholesterol, high taurine diet (HCHTD, CD +

  10. Reduced Estradiol-Induced Vasodilation and Poly-(ADP-Ribose) Polymerase (PARP) Activity in the Aortas of Rats with Experimental Polycystic Ovary Syndrome (PCOS)

    PubMed Central

    Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L.; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS. PMID:23555555

  11. S1 to S2 hind- and forelimb projections in the agouti somatosensory cortex: axon fragments morphological analysis.

    PubMed

    Santiago, L F; Rocha, E G; Santos, C L A; Pereira, A; Franca, J G; Picanço-Diniz, C W

    2010-12-01

    The integration of cutaneous, proprioceptive, and motor information in area S2 seems to be essential for manual object recognition and motor control. Part of the inputs to S2 comes from area S1. However no detailed investigations of the morphology of this projection are available. In the present study we describe and quantify the morphology of axon fragments of S1 to S2 ipsilateral projections in the agouti somatosensory cortex. Two groups of projecting axon arbors in S2 were individually reconstructed in three dimensions using Neurolucida, after a single electrophysiological guided BDA injection in either the forelimb (n=4) or the hindlimb (n=4). Electrophysiological mapping was performed 15 days after injections, allowing the localization of S2. Cluster analysis of 40 fragments after hindlimb and 40 after forelimb distinguished two clusters of terminals designated as type I and type II. On average, Type I fragments had greater surface areas and segment lengths than type II fragments, whereas type II fragments had higher number of terminal boutons, number of segments and branching points/mm than type I fragments. Type I corresponded to 58% of the axons projecting from the hindlimb representation in S1 whereas 63% of the sample originating from the forelimb representation in S1 corresponded to type II axons. The results suggest possible parallel processing by two stereotyped classes of axon terminals in the S1 to S2 projections that may represent at least part of the circuitry groundwork associated with distinct somatomotor skills of these limbs in agoutis. PMID:20932896

  12. Zerumbone, a tropical ginger sesquiterpene, ameliorates streptozotocin-induced diabetic nephropathy in rats by reducing the hyperglycemia-induced inflammatory response

    PubMed Central

    2013-01-01

    Background Zerumbone is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). The aim of the present study was to examine the effects of zerumbone in rats with streptozotocin-induced diabetic nephropathy (DN). Methods Diabetic rats were treated orally with zerumbone (20 or 40 mg/kg/day) for 8 weeks. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. Results Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by zerumbone. Zerumbone treatment was found to markedly improve histological architecture in the diabetic kidney. Hyperglycemia induced p38 mitogen-activated protein kinase activation, leading to increased infiltration of macrophages and increased levels of interleukin (IL)-1, IL-6 and tumor necrosis factor-?. All of the above abnormalities were reversed by zerumbone treatment, which also decreased the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, transforming growth factor-?1 and fibronectin in the diabetic kidneys. Conclusions The beneficial effect of zerumbone in rats with DN is at least in part through antihyperglycemia which was accompanied by inhibition of macrophage infiltration via reducing p38 mediated inflammatory response. PMID:24499158

  13. Exposure to hypergravity during the preweaning but not postweaning period reduces vestibular-related stress responses in rats.

    PubMed

    Abe, Chikara; Ueta, Yoichi; Morita, Hironobu

    2013-10-01

    Gravitational forces, including hypergravity or microgravity, induce plasticity of vestibular-related functions. These functions are not easily reversed if exposure to the gravitational forces occurs during vestibular development. In the present study, we hypothesized that vestibular-related stress responses might be suppressed in rats exposed to hypergravity during the vestibular development period. We exposed the rats to 2 g (hypergravity) during the preweaning (BW-HG; embryonic day 14 to postnatal week 3) or postweaning (AW-HG; postnatal weeks 4-6) periods. After recovery for 4 wk at 1 g, we conducted rotarod tests and then exposed the rats to 2 g for 90 min. In BW-HG rats, vestibular-related motor coordination on the rotarod test was partially, but not fully, restored to the level of AW-HG rats or rats raised at 1 g (1-G group). Loading-induced plasma adrenocorticotropic hormone and corticosterone levels were significantly suppressed in BW-HG and in rats with a vestibular lesion compared with AW-HG and 1-G rats. Arginine vasopressin and Fos expression levels in the paraventricular hypothalamic nucleus were also significantly lower in BW-HG and vestibular lesion rats than in AW-HG and 1-G rats. By contrast, there was no difference in the electrical foot shock-induced increase in plasma corticosterone among the experimental groups, suggesting that the nonvestibular-related stress response was not suppressed by exposure to 2 g during preweaning. These results indicated that exposure to hypergravity during preweaning specifically suppressed the vestibular-related stress response, and this suppression did not recover after 4 wk at 1 g. PMID:23908316

  14. Neural precursor cell transplantation enhances functional recovery and reduces astrogliosis in bilateral compressive/contusive cervical spinal cord injury.

    PubMed

    Wilcox, Jared T; Satkunendrarajah, Kajana; Zuccato, Jeffrey A; Nassiri, Farshad; Fehlings, Michael G

    2014-10-01

    Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation. PMID:25107585

  15. Burdock fermented by Aspergillus awamori elevates cecal Bifidobacterium, and reduces fecal deoxycholic acid and adipose tissue weight in rats fed a high-fat diet.

    PubMed

    Okazaki, Yukako; Sitanggang, Novita Vivi; Sato, Satoko; Ohnishi, Nanae; Inoue, Junji; Iguchi, Takafumi; Watanabe, Toshiro; Tomotake, Hiroyuki; Harada, Kazuki; Kato, Norihisa

    2013-01-01

    This study investigated the effects of dietary supplementation with burdock powder and Aspergillus awamori-fermented burdock powder at 5% on the intestinal luminal environment and body fat in rats fed a high-fat (HF) diet. Food intake and growth were unaffected by dietary manipulation. Consumption of the burdock and fermented burdock diets significantly elevated fecal IgA and mucins (indices of intestinal immune and barrier functions) and reduced fecal lithocholic acid (a risk factor for colon cancer) (p<0.05). The fermented burdock diet markedly elevated cecal Bifidobacterium and organic acids, including lactate, acetate, propionate, and butyrate, and reduced fecal deoxycholic acid (a risk factor for colon cancer) and perirenal adipose tissue weight (p<0.05), but the burdock diet did not. These results suggest that consumption of fermented burdock improves the intestinal luminal environment and suppresses obesity in rats fed a HF diet. PMID:23291748

  16. Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats.

    PubMed

    Dvir, I; Chayoth, R; Sod-Moriah, U; Shany, S; Nyska, A; Stark, A H; Madar, Z; Arad, S M

    2000-10-01

    The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food. PMID:11103217

  17. Insulin-like growth factor I reduces thyroid hormone receptors in the rat liver. Evidence for a feed-back loop regulating the peripheral thyroid hormone action

    Microsoft Academic Search

    C G Pellizas; A H Coleoni; M E Costamagna; M Di Fulvio; A M Masini-Repiso

    1998-01-01

    Tri-iodothyronine (T3) is known to be involved in the regulation of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis. In previous studies we demonstrated that IGF-I and GH reduced the metabolic response to T3 measured as the activity of two T3- dependent enzymes, mitochondrial Ć-glycerophosphate dehydrogenase (Ć-GPD) and cytosolic malic enzyme (ME) in cultured rat liver cells. In this

  18. Effect of Argemone mexicana (L.) against lithium-pilocarpine induced status epilepticus and oxidative stress in Wistar rats.

    PubMed

    Asuntha, G; Raju, Y Prasanna; Sundaresan, C R; Rasheed, Arun; Chowdary, V Harini; Vandana, K R; Babu, K Satish; Prasad, K V S R G

    2015-01-01

    Argemone mexicana (L.) has a role in the treatment of epileptic disorders in Indian traditional system of medicine. We studied its effect on induced status epilepticus (SE) and oxidative stress in rats. SE was induced in male albino rats by administration of pilocarpine (30 mg/kg, ip) 24 h after injection of lithium chloride (3 mEq/kg, ip). Different doses of the ethanol extract of A. mexicana were administered orally 1 h before the injection of pilocarpine. The severity of SE was observed and recorded every 15 min for 90 min and thereafter at every 30 min for another 90 min, using the Racine scoring system. In vivo lipid peroxidation of rat brain tissue was measured utilizing thiobarbiturate-reactive substances. Both in vitro free radical nitric oxide and 2,2-diphenyl-1-picryl hydrazyl scavenging activities of the extract were also determined. The SE severity was significantly reduced following oral administration of the extract at 250, 500 and 1000 mg/kg doses. None of the animals from groups 3 to 5 (with A. mexicana extract) have exhibited forelimb clonus of stage 4 seizure. The extract also exhibited both in vivo and in vitro antioxidant activities. PMID:25675709

  19. Hypothalamic Pituitary Adrenal Axis Responses to Low-Intensity Stressors are Reduced After Voluntary Wheel Running in Rats

    PubMed Central

    Campeau, S.; Nyhuis, T. J.; Sasse, S. K.; Kryskow, E. M.; Herlihy, L.; Masini, C. V.; Babb, J. A.; Greenwood, B. N.; Fleshner, M.; Day, H. E. W.

    2015-01-01

    Regular physical exercise is beneficial for both physical and mental health. By contrast, stress is associated with deleterious effects on health and there is growing evidence that regular physical exercise counteracts some of the effects of stress. However, most previous studies have suggested that prior exercise does not alter the acute hypothalamic pituitary adrenal (HPA) axis responses to stress. The present series of studies provides evidence that in rats, 6 weeks (but not 1 or 3 weeks) of voluntary wheel running reduces the HPA axis responses to lower-intensity stressors such as an i.p. saline injection, exposure to a novel environment or exposure to moderate intensity noise, but not to more intense stressors such as predator odour exposure or restraint. Daily exercise does not appear to be necessary for the reduction in HPA axis responses, with intermittent access (24 h out of each 72-h period) to a running wheel for 6 weeks, resulting in similar decrements in adrenocorticotrophic hormone and corticosterone release in response to 85 dBA noise exposure. Data from in situ hybridisation for c-fos mRNA are consistent with the hypothesis that voluntary exercise results in a decrease in HPA axis responsiveness to a low-intensity stressor at a central level, with no changes in primary sensory processing. Together, these data suggest that 6 weeks of daily or intermittent exercise constrains the HPA axis response to mild, but not more intense stressors, and that this regulation may be mediated at a central level beyond the primary sensory input. PMID:20406350

  20. Developmental exposure to cuprizone reduces intermediate-stage progenitor cells and cholinergic signals in the hippocampal neurogenesis in rat offspring.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-01

    The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male offspring had a decreased density of new glue2(+) oligodendrocyte progenitor cells in the dentate hilus and in the area of the cerebellar medulla in the presence of 0.4% CPZ. With regard to neurogenesis-related parameters, offspring had decreased T box brain 2(+) progenitor cells and increased apoptotic cells, as detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, which was accompanied by the up-regulation of Casp12 and Bcl2l11 in the subgranular zone, and increased reelin(+) interneurons in the dentate hilus. In addition, the density of phosphorylated TrkB(+) interneurons decreased in the dentate hilus, which was accompanied by transcript down-regulation of Bdnf and Chrna7 in the dentate gyrus. Moreover, granule cells expressing gene products of immediate-early genes, i.e., Arc and Fos, decreased. These results suggest that maternal exposure to 0.4% CPZ decreases proliferative type-2 progenitor cells via endoplasmic reticulum stress-mediated apoptosis and inhibition of cholinergic signals to intermediate-stage progenitor cells following reduced oligodendrocyte production and suppression of the brain-derived neurotrophic factor signaling cascade. Increases in reelin-expressing interneurons may compensate for impaired granule cell migration and/or correct positioning due to decreased immediate-early gene-mediated neuronal plasticity. However, all observed fluctuations disappeared at the adult stage, suggesting that CPZ-induced developmental neurotoxicity was reversible. PMID:25704630

  1. Is salamander limb regeneration really perfect? Anatomical and morphogenetic analysis of forelimb muscle regeneration in GFP-transgenic axolotls as a basis for regenerative, developmental, and evolutionary studies.

    PubMed

    Diogo, R; Nacu, E; Tanaka, E M

    2014-06-01

    The axolotl Ambystoma mexicanum is one of the most commonly used model organisms in developmental and regenerative studies because it can reconstitute what is believed to be a completely normal anatomical and functional forelimb/hindlimb after amputation. However, to date it has not been confirmed whether each regenerated forelimb muscle is really a "perfect" copy of the original muscle. This study describes the regeneration of the arm, forearm, hand, and some pectoral muscles (e.g., coracoradialis) in transgenic axolotls that express green fluorescent protein (GFP) in muscle fibers. The observations found that: (1) there were muscle anomalies in 43% of the regenerated forelimbs; (2) however, on average in each regenerated forelimb there are anomalies in only 2.5% of the total number of muscles examined, and there were no significant differences observed in the specific insertion and origin of the other muscles analyzed; (3) one of the most notable and common anomalies (seen in 35% of the regenerated forelimbs) was the presence of a fleshy coracoradialis at the level of the arm; this is a particularly outstanding configuration because in axolotls and in urodeles in general this muscle only has a thin tendon at the level of the arm, and the additional fleshy belly in the regenerated arms is strikingly similar to the fleshy biceps brachii of amniotes, suggesting a remarkable parallel between a regeneration defect and a major phenotypic change that occurred during tetrapod limb evolution; (4) during forelimb muscle regeneration there was a clear proximo-distal and radio-ulnar morphogenetic gradient, as seen in normal development, but also a ventro-dorsal gradient in the order of regeneration, which was not previously described in the literature. These results have broader implications for regenerative, evolutionary, developmental and morphogenetic studies. PMID:24692358

  2. Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats.

    PubMed

    Ravati, A; Junker, V; Kouklei, M; Ahlemeyer, B; Culmsee, C; Krieglstein, J

    1999-05-28

    Angiotensin-converting enzyme inhibitors have been demonstrated to protect spontaneously hypertensive rats from cerebral ischemia. The present study investigated the protective effect of enalapril and moexipril in models of permanent focal cerebral ischemia in normotensive mice and rats. To elucidate the mechanism of neuroprotection the influence of these angiotensin-converting enzyme inhibitors on glutamate-, staurosporine- or Fe2+/3+-induced generation of reactive oxygen species and neuronal cell death in primary cultures from chick embryo telencephalons was studied. Treatment with moexipril or enalapril dose-dependently reduced the percentage of damaged neurons, as well as mitochondrial reactive oxygen species generation induced by glutamate, staurosporine or Fe2+/3+. Furthermore, moexipril and enalapril attenuated staurosporine-induced neuronal apoptosis as determined by nuclear staining with Hoechst 33258. In mice, 1 h pretreatment with enalapril (0.03 mg/kg) or moexipril (0.3 mg/kg) significantly reduced brain damage after focal ischemia as compared to control animals. Additionally, moexipril (0.01 mg/kg) was able to reduce the infarct volume in the rat model after focal cerebral ischemia. The results of the present study indicate that the angiotensin-converting enzyme inhibitors enalapril and moexipril promote neuronal survival due to radical scavenging properties. PMID:10408248

  3. Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia.

    PubMed

    Chen, Chunhua; Ostrowski, Robert P; Zhou, Changman; Tang, Jiping; Zhang, John H

    2010-07-01

    We evaluated a role of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream genes in acute hyperglycemia-induced hemorrhagic transformation in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 280-300 g (n = 105) were divided into sham, 90 min middle cerebral artery occlusion (MCAO), MCAO plus HIF-1alpha inhibitors, 2-methoxyestradiol (2ME2) or 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), groups. Rats received an injection of 50% dextrose (6 ml/kg intraperitoneally) at 15 min before MCAO. HIF-1alpha inhibitors were administered at the onset of reperfusion. The animals were examined for neurological deficits and sacrificed at 6, 12, 24, and 72 hr following MCAO. The cerebral tissues were collected for histology, zymography, and Western blot analysis. The expression of HIF-1alpha was increased in ischemic brain tissues after MCAO and reduced by HIF-1alpha inhibitors. In addition, 2ME2 reduced the expression of vascular endothelial growth factor (VEGF) and the elevation of active matrix metalloproteinase-2 and -9 (MMP-2/MMP-9) in the ipsilateral hemisphere. Both 2ME2 and YC-1 reduced infarct volume and ameliorated neurological deficits. However, only 2ME2 attenuated hemorrhagic transformation in the ischemic territory. In conclusion, the inhibition of HIF-1alpha and its downstream genes attenuates hemorrhagic conversion of cerebral infarction and ameliorates neurological deficits after focal cerebral ischemia. PMID:20155812

  4. Treatment with the ?-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes.

    PubMed

    Mochizuki, Kazuki; Fukaya, Nanae; Tanaka, Yutaro; Fuchigami, Masahiro; Goda, Toshinao

    2011-11-01

    Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the ?-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the experimental period. Miglitol-treated rats had lower nonfasting blood glucose levels and higher 1,5-anhydroglucitol levels, a marker for glucose fluctuations, at week 40 than control rats. The gene expression of inflammatory cytokines including interleukin-6, tumor necrosis factor-?, and interferon-? in peripheral leukocytes gradually increased during the development of diabetes in control rats, but not in miglitol-treated rats. Our results suggest that dietary supplementation with miglitol from the preonset stage in OLETF rats improves glycemic control and reduces gene expression of cytokines related to inflammation in peripheral leukocytes. PMID:21550076

  5. Reduced transition between open and inactivated channel states underlies 5HT increased I(Na+) in rat nociceptors.

    PubMed

    d'Alcantara, Pablo; Cardenas, Luz M; Swillens, Stéphane; Scroggs, Reese S

    2002-07-01

    We previously demonstrated that activation of a 5HT(4) receptor coupled cAMP-dependent signaling pathway increases tetrodotoxin-resistant Na(+) current (I(Na)) in a nociceptor-like subpopulation of rat dorsal root ganglion cells (type 2). In the present study we used electrophysiology experiments and computer modeling studies to explore the mechanism(s) underlying the increase of I(Na) by 5HT. In electrophysiological experiments with type 2 dorsal root ganglion cells, 5HT increased peak I(Na) and the activation and inactivation rate, without significantly affecting the voltage dependency of activation or availability. Studies on the voltage dependency of channel availability, time course of removal of inactivation, and inactivation of evoked Na(+) currents suggested that there are at least two inactivation states of the Na(+) channel, one (I(fast)) that is induced and retrieved faster than the other (I(slow)). Long (1 s), but not short (60 or 100 ms), inactivating conditioning pulses (CPs) suppressed the 5HT-induced increase in I(Na). Computer modeling studies suggest that 5HT increased I(Na) mainly by decreasing the transition rate (k(OI1)) from an open state to I(fast). Furthermore, 5HT increased I(Na) activation and inactivation rates mainly by increasing the transition rate from closed to open (k(C3O)) and from I(fast) to I(slow) (k(I1I2)), respectively. The antagonism of the 5HT-induced increase in I(Na) by 1-s inactivation CPs may be due an enhancement of transitions from I(fast) to I(slow), via the increase in k(I1I2). This may deplete the pool of channels residing in I(fast), reducing the frequency of reopenings from I(fast), which offsets the increase in I(Na) produced by the reduction in k(OI1). The above findings fit well with previous studies showing that activation of the cAMP/PKA cascade simultaneously increases voltage sensitive tetrodotoxin-resistant Na(+) conductance and inactivation rate in nociceptors. The antagonism of the effects of 5HT by long inactivation CPs suggests that drugs designed to induce and/or stabilize the I(slow) state might be useful for reducing hyperalgesia produced by inflammatory mediators. PMID:12080097

  6. Reduced transition between open and inactivated channel states underlies 5HT increased I(Na+) in rat nociceptors.

    PubMed Central

    d'Alcantara, Pablo; Cardenas, Luz M; Swillens, Stéphane; Scroggs, Reese S

    2002-01-01

    We previously demonstrated that activation of a 5HT(4) receptor coupled cAMP-dependent signaling pathway increases tetrodotoxin-resistant Na(+) current (I(Na)) in a nociceptor-like subpopulation of rat dorsal root ganglion cells (type 2). In the present study we used electrophysiology experiments and computer modeling studies to explore the mechanism(s) underlying the increase of I(Na) by 5HT. In electrophysiological experiments with type 2 dorsal root ganglion cells, 5HT increased peak I(Na) and the activation and inactivation rate, without significantly affecting the voltage dependency of activation or availability. Studies on the voltage dependency of channel availability, time course of removal of inactivation, and inactivation of evoked Na(+) currents suggested that there are at least two inactivation states of the Na(+) channel, one (I(fast)) that is induced and retrieved faster than the other (I(slow)). Long (1 s), but not short (60 or 100 ms), inactivating conditioning pulses (CPs) suppressed the 5HT-induced increase in I(Na). Computer modeling studies suggest that 5HT increased I(Na) mainly by decreasing the transition rate (k(OI1)) from an open state to I(fast). Furthermore, 5HT increased I(Na) activation and inactivation rates mainly by increasing the transition rate from closed to open (k(C3O)) and from I(fast) to I(slow) (k(I1I2)), respectively. The antagonism of the 5HT-induced increase in I(Na) by 1-s inactivation CPs may be due an enhancement of transitions from I(fast) to I(slow), via the increase in k(I1I2). This may deplete the pool of channels residing in I(fast), reducing the frequency of reopenings from I(fast), which offsets the increase in I(Na) produced by the reduction in k(OI1). The above findings fit well with previous studies showing that activation of the cAMP/PKA cascade simultaneously increases voltage sensitive tetrodotoxin-resistant Na(+) conductance and inactivation rate in nociceptors. The antagonism of the effects of 5HT by long inactivation CPs suggests that drugs designed to induce and/or stabilize the I(slow) state might be useful for reducing hyperalgesia produced by inflammatory mediators. PMID:12080097

  7. Tesaglitazar, a Dual Peroxisome Proliferator- Activated Receptor Agonist (PPAR?\\/?), Improves Metabolic Abnormalities and Reduces Renal Injury in Obese Zucker Rats

    Microsoft Academic Search

    Jie Liao; Zohreh Soltani; Philip Ebenezer; Angel A. Isidro-Carrión; Rubin Zhang; Arshad Asghar; Erwin Aguilar; Joseph Francis; Xuejiao Hu; León Ferder; Efrain Reisin

    2010-01-01

    Metabolic syndrome increases the risk of developing diabetes as well as cardiovascular and kidney diseases. This research studied the effects of tesaglitazar, a dual-acting peroxisome proliferator-activated receptor (PPAR)?\\/? agonist, on metabolic abnormalities and kidney injury in obese Zucker rats (OZR). Lean Zucker rats (LZR) and OZR were used as control groups. Tesaglitazar (1 ?mol\\/kg\\/day) was given for 8 weeks in

  8. Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat

    Microsoft Academic Search

    B Topic; E Tani; K Tsiakitzis; P. N Kourounakis; E Dere; R. U Hasenöhrl; R Häcker; C. M Mattern; J. P Huston

    2002-01-01

    Here we assessed the effects of i.g. administration of Zingicomb (ZC), a mixture of zingiber officinale and ginkgo biloba extracts, on learning and memory, and on indicators of oxidative stress in aged rats. Effects of ZC (1 and 10 mg\\/kg) were investigated in 22–24 months old Wistar rats using the Morris water maze, in which they show deficient performance as

  9. Na+\\/H+ Exchanger1 Inhibitors Reduce Neuronal Excitability and Alter Na+ Channel Inactivation Properties in Rat Primary Sensory Neurons

    Microsoft Academic Search

    Chang-Ning Liu; Chris J. Somps

    2008-01-01

    Inhibitors of the Na1\\/H1 exchanger isoform 1 (NHE-1) have been associated with peripheral neuropathy in rats and dogs. Recent studies suggest that NHE-1 plays an important role in mediating neuronal excitability. To investigate potential NHE-1-mediated mechanisms contributing to neuronal toxicity, we studied the effects of NHE-1 inhibitors on nerve and dorsal root ganglion (DRG) neurons isolated from the adult rat.

  10. Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h\\/day access to nicotine

    Microsoft Academic Search

    Mark G. LeSage; Dan E. Keyler; Don Shoeman; Donna Raphael; Gregory Collins; Paul R. Pentel

    2002-01-01

    The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h\\/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine

  11. Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats1

    Microsoft Academic Search

    Sin H. Gieng; Michael H. Green; Joanne B. Green; Francisco J. Rosales

    Vitamin A (VA) kinetics was studied in rats with marginal VA stores before, during, and after inflammation. Rats received orally (11,12-3H(N))retinol ((3H)VA; day 0), and inflammation was induced on day 21 with lipopoly- sacchride (LPS) for 3 days (n 5 5) or recombinant human interleukin-6 (rhIL-6) for 7 days (n 5 5). Both the fraction of (3H)VA and retinol concentrations

  12. Ossification Pattern of Estuarine Dolphin (Sotalia guianensis) Forelimbs, from the Coast of the State of Espírito Santo, Brazil

    PubMed Central

    Botta, Silvina; de Queiroz, Fábio Ferreira; Campos, Adélia Sepúlveda

    2015-01-01

    The estuarine dolphin, Sotalia guianensis, is one of the most abundant cetacean species in Brazil. Determination of age and of aspects associated with the development of this species is significant new studies. Counts of growth layer groups in dentin are used to estimate age of these animals, though other ways to evaluate development are also adopted, like the measurement of total length (TL). This study presents a procedure to evaluate the development of the estuarine dolphin based on the ossification pattern of forelimbs. Thirty-seven estuarine dolphins found in the state of Espírito Santo, Brazil, were examined. Age was estimated, TL was measured and ossification of epiphyses was examined by radiography. We analyzed results using the Spearman correlation. Inspection of radiographs allowed evaluation of the significance of the correlation between age and development of the proximal (r = 0.9109) and distal (r = 0.9092) radial epiphyses, and of the distal ulnar epiphyses (r = 0.9055). Radiographic analysis of forelimbs proved to be an appropriate method to evaluate physical maturity, and may be a helpful tool to estimate age of these animals in ecological and population studies. PMID:26017269

  13. Habitual use of the primate forelimb is reflected in the material properties of subchondral bone in the distal radius

    PubMed Central

    Carlson, Kristian J; Patel, Biren A

    2006-01-01

    Bone mineral density is directly proportional to compressive strength, which affords an opportunity to estimate in vivo joint load history from the subchondral cortical plate of articular surfaces in isolated skeletal elements. Subchondral bone experiencing greater compressive loads should be of relatively greater density than subchondral bone experiencing less compressive loading. Distribution of the densest areas, either concentrated or diffuse, also may be influenced by the extent of habitual compressive loading. We evaluated subchondral bone in the distal radius of several primates whose locomotion could be characterized in one of three general ways (quadrupedal, suspensory or bipedal), each exemplifying a different manner of habitual forelimb loading (i.e. compression, tension or non-weight-bearing, respectively). We employed computed tomography osteoabsorptiometry (CT-OAM) to acquire optical densities from which false-colour maps were constructed. The false-colour maps were used to evaluate patterns in subchondral density (i.e. apparent density). Suspensory apes and bipedal humans had both smaller percentage areas and less well-defined concentrations of regions of high apparent density relative to quadrupedal primates. Quadrupedal primates exhibited a positive allometric effect of articular surface size on high-density area, whereas suspensory primates exhibited an isometric effect and bipedal humans exhibited no significant relationship between the two. A significant difference between groups characterized by predominantly compressive forelimb loading regimes vs. tensile or non-weight-bearing regimes indicates that subchondral apparent density in the distal radial articular surface distinguishes modes of habitually supporting of body mass. PMID:16761969

  14. Forelimb muscle function in pig-nosed turtles, Carettochelys insculpta: testing neuromotor conservation between rowing and flapping in swimming turtles.

    PubMed

    Rivera, Angela R V; Blob, Richard W

    2013-10-23

    Changes in muscle activation patterns can lead to new locomotor modes; however, neuromotor conservation-the evolution of new forms of locomotion through changes in structure without concurrent changes to underlying motor patterns-has been documented across diverse styles of locomotion. Animals that swim using appendages do so via rowing (anteroposterior oscilations) or flapping (dorsoventral oscilations). Yet few studies have compared motor patterns between these swimming modes. In swimming turtles, propulsion is generated exclusively by limbs. Kinematically, turtles swim using multiple styles of rowing (freshwater species), flapping (sea turtles) and a unique hybrid style with superficial similarity to flapping by sea turtles and characterized by increased dorsoventral motions of synchronously oscillated forelimbs that have been modified into flippers (Carettochelys insculpta). We compared forelimb motor patterns in four species of turtle (two rowers, Apalone ferox and Trachemys scripta; one flapper, Caretta caretta; and Carettochelys) and found that, despite kinematic differences, motor patterns were generally similar among species with a few notable exceptions: specifically, presence of variable bursts for pectoralis and triceps in Trachemys (though timing of the non-variable pectoralis burst was similar), and the timing of deltoideus activity in Carettochelys and Caretta compared with other taxa. The similarities in motor patterns we find for several muscles provide partial support for neuromotor conservation among turtles using diverse locomotor styles, but the differences implicate deltoideus as a prime contributor to flapping limb motions. PMID:23966596

  15. (-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability.

    PubMed

    Litterio, Maria C; Vazquez Prieto, Marcela A; Adamo, Ana M; Elesgaray, Rosana; Oteiza, Patricia I; Galleano, Monica; Fraga, Cesar G

    2015-07-01

    This work investigated the blood pressure (BP)-lowering effect of the flavanol (-)-epicatechin in a model of metabolic syndrome. Rats were fed a regular chow diet without (Control) or with 10% (w/v) fructose in the drinking water (high fructose, HF) for 8 weeks. A subgroup of the HF-fed rats was supplemented with (-)-epicatechin 20 mg/kg body weight (HF-EC). Dietary (-)-epicatechin reverted the increase in BP caused by the fructose treatment. In aorta, superoxide anion production and the expression of the NADPH oxidase (NOX) subunits p47(phox) and p22(phox) were enhanced in the HF-fed rats. The increase was prevented by (-)-epicatechin. Similar profile was observed for NOX4 expression. The activity of aorta nitric oxide synthase (NOS) was increased in the HF group and was even higher in the HF-EC rats. These effects were paralleled by increased endothelial NOS phosphorylation at the activation site Ser1177. Among the more relevant mitogen-activated protein kinase pathways in vascular tissue, c-Jun-N-terminal kinase was shown to be activated in the aorta of the HF-fed rats, and (-)-epicatechin supplementation mitigated this activation. Thus, the results suggest that dietary (-)-epicatechin supplementation prevented hypertension in HF-fed rats, decreasing superoxide anion production and elevating NOS activity, favoring an increase in NO bioavailability. PMID:25943039

  16. Treatment with the ?-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes

    Microsoft Academic Search

    Kazuki Mochizuki; Nanae Fukaya; Yutaro Tanaka; Masahiro Fuchigami; Toshinao Goda

    2011-01-01

    Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the ?-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control

  17. Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.

    PubMed

    Pang, Yi; Tien, Lu-Tai; Zhu, Hobart; Shen, Juying; Wright, Camilla F; Jones, Tembra K; Mamoon, Samir A; Bhatt, Abhay J; Cai, Zhengwei; Fan, Lir-Wan

    2015-01-01

    Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1? (IL-1?) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1? may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1? might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure. PMID:25898410

  18. Tissue oxygen is reduced in white matter of spontaneously hypertensive-stroke prone rats: a longitudinal study with electron paramagnetic resonance

    PubMed Central

    Weaver, John; Jalal, Fakhreya Y; Yang, Yi; Thompson, Jeffrey; Rosenberg, Gary A; Liu, Ke J

    2014-01-01

    Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O2 is critical in brain physiology, tissue O2 level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO2) in the deep WM. We tested this hypothesis by monitoring WM tissue pO2 using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO2 from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO2 to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO2 was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO2 may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO2 in the WM of small animals. PMID:24549186

  19. Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

    PubMed Central

    Pang, Yi; Tien, Lu-Tai; Zhu, Hobart; Shen, Juying; Wright, Camilla F.; Jones, Tembra K.; Mamoon, Samir A.; Bhatt, Abhay J.; Cai, Zhengwei; Fan, Lir-Wan

    2015-01-01

    Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1? (IL-1?) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1? may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1? might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure. PMID:25898410

  20. The sigma agonist 1,3-di-o-tolyl-guanidine reduces the morphological and behavioral changes induced by neonatal ventral hippocampus lesion in rats.

    PubMed

    Jaramillo-Loranca, Blanca Estela; Garcés-Ramírez, Linda; Munguía Rosales, Alicia Angélica; Luna Ramírez, Carolina; Vargas Hernández, Genaro; Morales-Dionisio, Oscar; González-Elizalde, Kateri; Flores, Gonzalo; Zamudio, Sergio; De La Cruz-López, Fidel

    2015-04-01

    Sigma (?) receptors have generated a great deal of interest due to their possible role in psychosis, neuroprotection, and various other behaviors including addictive processes. Sigma receptors have been located in brain areas involved in motor functions, including the dopaminergic projections from the substantia nigra to the striatum. Evidence suggests that one of their major roles might be to regulate the activity of the glutamatergic system via the N-methyl-D-aspartate receptor. The sigma receptor agonist 1,3-di-o-tolyl-guanidine (DTG) was found to increase dopamine release in the striatum, nucleus accumbens, and prefrontal cortex, in a dose-dependent manner, after central as well as peripheral administration, suggesting a modulatory role of these receptors on the dopaminergic system. The present study examines whether chronic administration of the DTG sigma agonist induces neuromorphological and behavioral changes in neonatal ventral hippocampal lesioned (nVHL) rats as a neurodevelopmental model of schizophrenia. The results show that the DTG administration reduces the hyperlocomotor activity in nVHL rats and reverses the neuronal hypotrophy generated in nVHL rats in the prefrontal cortex, amygdala, and nucleus accumbens. Our results demonstrate that DTG, a sigma-1 receptor agonist, reverses some of the behavioral and neuromorphological effects of nVHL on the rat and supports the possibility that DTG may have beneficial effects in the management of symptoms of schizophrenia. PMID:25682743

  1. Insulin-Like Growth Factor-1 (IGF-1) Reduces ischemic changes and increases circulating angiogenic factors in experimentally - induced myocardial infarction in rats

    PubMed Central

    2011-01-01

    Background Coronary artery disease is a global health concern in the present day with limited therapies. Extensive efforts have been devoted to find molecular therapies to enhance perfusion and function of the ischemic myocardium. Aim of the present study was to look into the effects of insulin like growth factor -1 (IGF-1) on circulating angiogenic factors after myocardial ischemia in rats. Methods Adult male Sprague-Dawley rats were randomly divided into 10-days control, myocardial infarction, IGF-1 alone (2 ?g/rat/day) and ISO+IGF-1 groups. Isoproterenol (ISO), a synthetic catecholamine was used to induce myocardial infarction. Serum transforming growth factor-? (TGF-?) and vascular endothelial growth factor (VEGF) levels were checked after 10-days of IGF-1 administration. Results There was a significant increase in heart weight after IGF-1 treatment. A significant increase in cardiac enzyme level (CK-MB and LDH) was seen in isoproterenol treated rats when compared to control group. IGF-1treatment induced a significant increase in serum angiogenic factors, IGF-1, VEGF and TGF beta levels. IGF-1 also reduced the ischemic changes in the myocardium when compared to the isoproterenol alone treated group. Conclusions In conclusion, treatment with insulin-like growth factor-1 (IGF-1) in myocardial infarction significantly increased circulating angiogenic growth factors like IGF-1, VEGF and TGF beta thus, protecting against myocardial ischemia. PMID:21651821

  2. The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats.

    PubMed

    Kim, Min Jung; Park, Jong-Heum; Kwon, Dae Young; Yang, Hye Jeong; Kim, Da Sol; Kang, Suna; Shin, Bae Keun; Moon, Na Rang; Song, Beom-Seok; Kim, Jae-Hun; Park, Sunmin

    2015-04-01

    Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women. PMID:25258426

  3. Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels in ovariectomized rats.

    PubMed

    Li, Yong-Qi; Ji, Hui; Shen, Yang; Ding, Li-Ju; Zhuang, Pei; Yang, Yu-Lin; Huang, Qiu-Ju

    2009-01-01

    Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-beta1 (TGF-beta1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1-L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-beta1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-beta1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-beta1 levels and did not accelerate ovariectomy-induced bone loss in rats. PMID:19142215

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

    SciTech Connect

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

    1985-07-01

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

  5. Emu Oil Reduces Small Intestinal Inflammation in the Absence of Clinical Improvement in a Rat Model of Indomethacin-Induced Enteropathy

    PubMed Central

    Abimosleh, Suzanne M.; Tran, Cuong D.; Howarth, Gordon S.

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5?mL; days 0–12) and with 0.5?mL Water or the NSAID, Indomethacin (8?mg/kg; days 5–12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  6. Emu oil reduces small intestinal inflammation in the absence of clinical improvement in a rat model of indomethacin-induced enteropathy.

    PubMed

    Abimosleh, Suzanne M; Tran, Cuong D; Howarth, Gordon S

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5?mL; days 0-12) and with 0.5?mL Water or the NSAID, Indomethacin (8?mg/kg; days 5-12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10-12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  7. Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats

    PubMed Central

    Hamakawa, Michiru; Ishida, Akimasa; Tamakoshi, Keigo; Shimada, Haruka; Nakashima, Hiroki; Noguchi, Taiji; Toyokuni, Shinya; Ishida, Kazuto

    2013-01-01

    Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury. PMID:23874064

  8. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    PubMed

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. PMID:22727564

  9. Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin

    PubMed Central

    Mitchell, Nicole J.; Xue, Kathy S.; Lin, Shuhan; Marroquin-Cardona, Alicia; Brown, Kristal A.; Elmore, Sarah E.; Tang, Lili; Romoser, Amelia; Gelderblom, Wentzel C. A.; Wang, Jia-Sheng; Phillips, Timothy D.

    2014-01-01

    Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the GI tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer-344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25 or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1/kg b.w. and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1-albumin, urinary AF (AFM1), and FB1 biomarkers over a period of 72 hr. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging between 45 to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67 and 45% respectively, but increased levels of AFB1-albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects. PMID:24193864

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

    PubMed Central

    2011-01-01

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

  11. Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7–9

    PubMed Central

    HAN, TAO; HU, ZHONGHUA; TANG, YONGZHONG; SHRESTHA, ALISHA; OUYANG, WEN; LIAO, QIN

    2015-01-01

    The aim of the present study was to investigate the roles of Rho protein A (RhoA) and Rho kinases 2 (ROCK2) in the memory dysfunction of adult rats exposed to sevoflurane at postnatal days 7–9 (P7-9). One-week-old Sprague-Dawley rats were divided into four groups known as C, S1, S3 and F. Rats in the S1 (2 h at P7) and S3 groups (2 h/day at P7-9) were exposed to sevoflurane. The rats in the F group were treated with the ROCK2 inhibitor and subsequent sevoflurane exposure (2 h/day at P7-9). The rats in the C group received no sevoflurane. The protein levels of RhoA, ROCK2 and cleaved caspase-3 (Cl-Csp3) in the adult hippocampus were assessed by western blot analysis. Learning and memory of rats at postnatal 45–50 days (P45-50) were detected by the Morris water maze (MWM) test. During the training of MWM, the latency and distance of rats in the S3 group were significantly longer than that of the C group (P<0.05, respectively). In the probe test, the percentages of time and distance in the target quadrant for the S3 group were evidently less than that of the C group (P<0.05). There was no significant difference in the behaviors between the C and S1 groups (P>0.05, respectively). Corresponding to the behavioral changes, the levels of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S3 group significantly increased, compared to that of the C and S1 groups (P<0.05). Additionally, the ROCK2 inhibitor clearly decreased ROCK2 and Cl-Csp3 expression and shortened the latency during the training (P<0.05, P46-49 respectively) and probe test (P<0.05) in the F group, compared to that of the S3 group. Compared to the C group, the expression of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S1 group had no significant difference (P>0.05). Multiple inhalation of sevoflurane can induce neurotoxicity and memory dysfunction. RhoA and ROCK2 played important roles in the impairment of learning and memory of adults rats exposed to sevoflurane at the postnatal early stage.

  12. Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet

    Microsoft Academic Search

    Hidehiko Yokogoshi; H. Oda

    2002-01-01

    Summary.  ?The effect of taurine on hypercholesterolemia induced by feeding a high-cholesterol (HC) diet (10?g\\/kg) to rats was examined.\\u000a When taurine was supplemented to HC for 2?wk, serum total cholesterol significantly decreased and serum HDL-cholesterol increased\\u000a compared with the HC diet group. In the hypercholesterolemic rats fed the HC diet, the excretion of fecal bile acids and hepatic\\u000a cholesterol 7?-hydroxylase (CYP7A1)

  13. Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats

    Microsoft Academic Search

    J. Edward Hsu; Theresa A. Jones

    2006-01-01

    Some studies have found that unilateral cerebral damage produces significant deficits in the ipsilesional, “less-affected”, body side. Other studies have found that such damage results in a paradoxical hyperfunctionality of the ipsilesional body side and a facilitation of learning-induced neuroplastic changes in the contralesional motor cortex. The purpose of this study was to determine whether these effects co-exist and\\/or vary

  14. Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats.

    PubMed

    Seymour, E Mitchell; Bennink, Maurice R; Bolling, Steven F

    2013-09-01

    Intake of phytochemical-rich diets is inversely related to hypertension. Phytochemicals alter in vitro aryl hydrocarbon receptor (AhR) and NF-E2 related factor (nrf2) transcription factor activity and related genes pertinent to antioxidant defense. However, it is unknown if these molecular effects occur in the heart with dietary intake of physiologically relevant phytochemicals and if this correlates with reduced hypertension-associated heart failure. This extended feeding study used whole grapes as a model of a phytochemical-rich food and hypertensive heart failure-prone rats to assess mechanisms of effect. Grape intake reduced cardiac hypertrophy and fibrosis and improved diastolic function. At the development of diastolic dysfunction, hypertensive rats show reduced AhR activity, reduced expression of AhR-regulated genes, reduced glutathione and reduced activity of glutathione-regulating proteins. However, grape intake significantly increased cardiac AhR and nrf2 activity, Phase I/II gene transcripts and protein activity related to antioxidant defense. Heart failure is the leading cause of morbidity and mortality in the aged and the intake of phytochemicals from fruits and vegetables decreases with age. Concentrated antioxidant nutrient trials have failed to affect heart failure. However, this study demonstrates that diet-relevant intake of non-nutrient phytochemicals significantly reduces heart failure progression. Therefore, this study suggests that higher intake of phytochemical-containing foods may achieve cardiac benefits that isolated antioxidant supplements may not. In summary, intake of diet-relevant phytochemicals altered the cardiac antioxidant transcriptome, antioxidant defense, oxidative damage and fibrosis. Regular phytochemical intake may therefore increase cardiac resistance to cardiac pathology instigated by prolonged hypertension. PMID:23528973

  15. Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma

    Microsoft Academic Search

    Kazuhiro Matsushita; Yasuhiro Kuramitsu; Youichi Ohiro; Manabu Obara; Masanobu Kobayashi; Yong-Qing Li; Masuo Hosokawa

    1998-01-01

    Synergistic effects of active hexose correlated compound (AHCC) extracted from mushroom on the treatment with UFT against mammary adenocarcinoma, SST-2 cells, In congenitally T cell-depressed spontaneously hypertensive rats (SHR) were observed. AHCC plus UFT had slighted but significant effects on the growth of primary tumors. Pulmonary metastases were not inhibited by the treatment with AHCC plus UFT, whereas metastases to

  16. Vagus nerve stimulation in awake rats reduces formalin-induced nociceptive behaviour and fos-immunoreactivity in trigeminal nucleus caudalis

    Microsoft Academic Search

    C Bohotin; M Scholsem; S Multon; D Martin; V Bohotin; J Schoenen

    2003-01-01

    Besides its well-established efficacy in epilepsy, vagus nerve stimulation (VNS) may be of potential interest in pain treatment. It has, however, not yet been assessed in animal pain models with the devices and stimulation protocols used in humans. We have therefore studied in awake rats the effects of left cervical VNS on trigeminal nociception using an implantable electrode and stimulator

  17. Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalus

    Microsoft Academic Search

    K. C. Somera; H. C. Jones

    2004-01-01

    The H-Tx rat has fetal-onset hydrocephalus associated with closure of the cerebral aqueduct and a reduction in the secretory cells of the subcommissural organ (SCO), a circumventricular organ situated in the dorsal wall of the cerebral aqueduct. The objective of this study was to determine the role of the SCO in hydrocephalus pathogenesis. Serial brain sections through aqueduct regions containing

  18. In utero glucocorticoid exposure reduced fetal skeletal muscle mass in rats independent of effects on maternal nutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n ...

  19. Interferon-Beta Blocks Infiltration of Inflammatory Cells and Reduces Infarct Volume After Ischemic Stroke in the Rat

    Microsoft Academic Search

    Wouter B. Veldhuis; Joris W. Derksen; Sarah Floris; Peter H. van der Meide; Helga E. de Vries; Janneke Schepers; Ine M. P. Vos; Christien D. Dijkstra; L. Jaap Kappelle; Klaas Nicolay; Peter R Bär

    2003-01-01

    The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-?), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI)

  20. Lipid-soluble smoke particles damage endothelial cells and reduce endothelium-dependent dilatation in rat and man

    Microsoft Academic Search

    Jin-Yan Zhang; Yong-Xiao Cao; Cang-Bao Xu; Lars Edvinsson

    2006-01-01

    BACKGROUND: Cigarette smoking is a strong risk factor for vascular disease and known to cause dysfunction of the endothelium. However, the molecular mechanisms involved are still not fully understood. METHODS: In order to reveal the direct effects of lipid-soluble smoke particles on the endothelium, ring segments isolated from rat mesenteric arteries and human middle cerebral arteries (MCA) obtained at autopsy

  1. Intragastric infusion of pea-protein hydrolysate reduces test-meal size in rats more than pea protein

    Microsoft Academic Search

    Doreen Häberer; Maria Tasker; Martin Foltz; Nori Geary; Margriet Westerterp; Wolfgang Langhans

    2011-01-01

    Because protein hydrolysates are digested faster than the corresponding proteins, they may increase or hasten the acute eating-inhibitory effect of protein. Potential mediating mechanisms include accelerated or greater release of satiating gut peptides and activation of metabolic signals that inhibit eating. We tested these hypotheses in adult male rats that were surgically equipped with intragastric (IG) cannulas and adapted to

  2. Nicotine and elevated body temperature reduce the complexity of the genioglossus and diaphragm EMG signals in rats during early maturation

    NASA Astrophysics Data System (ADS)

    Akkurt, David; Akay, Yasemin M.; Akay, Metin

    2009-10-01

    In this paper, we examined the effect of nicotine exposure and increased body temperature on the complexity (dynamics) of the genioglossus muscle (EMGg) and the diaphragm muscle (EMGdia) to explore the effects of nicotine and hyperthermia. Nonlinear dynamical analysis of the EMGdia and EMGg signals was performed using the approximate entropy method on 15 (7 saline- and 8 nicotine-treated) juvenile rats (P25-P35) and 19 (11 saline- and 8 nicotine-treated) young adult rats (P36-P44). The mean complexity values were calculated over the ten consecutive breaths using the approximate entropy method during mild elevated body temperature (38 °C) and severe elevated body temperature (39-40 °C) in two groups. In the first (nicotine) group, rats were treated with single injections of nicotine enough to produce brain levels of nicotine similar to those achieved in human smokers (2.5 (mg kg-1)/day) until the recording day. In the second (control) group, rats were treated with injections of saline, beginning at postnatal 5 days until the recording day. Our results show that warming the rat by 2-3 °C and nicotine exposure significantly decreased the complexity of the EMGdia and EMGg for the juvenile age group. This reduction in the complexity of the EMGdia and EMGg for the nicotine group was much greater than the normal during elevated body temperatures. We speculate that the generalized depressive effects of nicotine exposure and elevated body temperature on the respiratory neural firing rate and the behavior of the central respiratory network could be responsible for the drastic decrease in the complexity of the EMGdia and EMGg signals, the outputs of the respiratory neural network during early maturation.

  3. Exposure to particular matter increases susceptibility to respiratory Staphylococcus aureus infection in rats via reducing pulmonary natural killer cells.

    PubMed

    Zhao, Hui; Li, Wenxing; Gao, Yanfeng; Li, Jianqiang; Wang, Haibin

    2014-11-01

    Epidemiological studies have shown a correlation between exposure to fine particular matter (PM2.5) and increased respiratory infection, but the mechanisms have remained poorly defined. By using an experimental system we evaluated the effect of PM2.5 exposure on susceptibility to subsequent pulmonary Staphylococcus aureus (S. aureus) infection and its potential mechanisms. Rats were intratracheally instilled with a single dose of PM2.5 sample or PBS followed by an intratracheal inoculation with bacteria S. aureus at 24h after PM2.5 exposure. The rats were examined at 24h post infection. We found that exposure of rats to PM2.5 significantly increased inflammatory cells and levels of IL-6 and TNF-? in bronchoalveolar lavage fluids (BALF). Prior PM2.5 exposure markedly increased the susceptibility of rats to subsequent S. aureus infection. The mechanistic studies showed that alveolar macrophages (AMs) from PM2.5-experienced lungs had depressed phagocytosis of S. aureus, and prior PM2.5 exposure significantly decreased the natural killer (NK) cells recruited into the airways following subsequent S. aureus infection. Further, adoptive transfer of naive NK cells to the lung of prior PM2.5-exposed rats restored PM2.5-impaired antibacterial host defense. The presence of NK cells markedly enhanced the ability of AMs to phagocytose S. aureus ex vivo. Thus, our study identifies PM2.5-impaired NK cell response in the lung to be a novel critical mechanism for PM2.5-mediated susceptibility to S. aureus bacterial infection, which provides a potential mechanism to explain the epidemiological findings that associate ambient air pollution and increased lung bacterial infections. Our findings also suggest that enhancing pulmonary NK cells may be considered for future therapeutic approaches to clinically antibiotic-resistant S. aureus infection in the lung. PMID:25220797

  4. Reduced sleep and impaired sleep initiation in adult male rats exposed to alcohol during early postnatal period

    PubMed Central

    Volgin, Denys V.; Kubin, Leszek

    2012-01-01

    Prenatal alcohol exposure (AE) is associated with cognitive and neurobehavioral abnormalities, such as increased motor activity and elevated anxiety, that may last a lifetime. Persistent sleep disruption may underlie these problems. Using a rat model, we investigated long-term alterations of sleep-wake behavior following AE during a critical early developmental period. Male rats received 2.6 g/kg of alcohol intragastrically twice daily on postnatal days (PD) 4-9, a developmental period equivalent to the third trimester of human pregnancy (AE group), or were sham-intubated (S group). On PD52-80, they were instrumented for tethered electroencephalogram and nuchal electromyogram recording and habituated to the recording procedures. Sleep-wake behavior was then recorded during one 24 h-long session. Wake, slow-wave sleep (SWS) and rapid eye movement sleep (REMS) were scored in 10 s epochs during 6 h of the lights-on (rest) and 6 h of the lights-off (active) periods. During the active period, REMS percentage was significantly lower (4.7±0.9 (SE) vs. 8.2±0.9; p<0.02) and the percentage of SWS tended to be lower (p=0.07) in AE than S rats (N=6/group). During the rest period, sleep and wake amounts did not differ between the groups, but AE rats had longer latency to both SWS and REMS onset (p=0.02 and 0.003, respectively). Our data demonstrate that, in a rat model of prenatal AE, impaired sleep-wake behavior persists into the adulthood. Disordered sleep may exacerbate cognitive and behavioral disorders seen in human victims of prenatal AE. PMID:22698707

  5. Forelimb kinematics during swimming in the pig-nosed turtle, Carettochelys insculpta, compared with other turtle taxa: rowing versus flapping, convergence versus intermediacy.

    PubMed

    Rivera, Angela R V; Rivera, Gabriel; Blob, Richard W

    2013-02-15

    Animals that swim using appendages do so by way of rowing and/or flapping motions. Often considered discrete categories, rowing and flapping are more appropriately regarded as points along a continuum. The pig-nosed turtle, Carettochelys insculpta, is unusual in that it is the only freshwater turtle to have limbs modified into flippers and swim via synchronous forelimb motions that resemble dorsoventral flapping, traits that evolved independently from their presence in sea turtles. We used high-speed videography to quantify forelimb kinematics in C. insculpta and a closely related, highly aquatic rower (Apalone ferox). Comparisons of our new data with those previously collected for a generalized freshwater rower (Trachemys scripta) and a flapping sea turtle (Caretta caretta) allow us to: (1) more precisely quantify and characterize the range of limb motions used by flappers versus rowers, and (2) assess whether the synchronous forelimb motions of C. insculpta can be classified as flapping (i.e. whether they exhibit forelimb kinematics and angles of attack more similar to closely related rowing species or more distantly related flapping sea turtles). We found that the forelimb kinematics of previously recognized rowers (T. scripta and A. ferox) were most similar to each other, but that those of C. insculpta were more similar to rowers than to flapping C. caretta. Nevertheless, of the three freshwater species, C. insculpta was most similar to flapping C. caretta. 'Flapping' in C. insculpta is achieved through humeral kinematics very different from those in C. caretta, with C. insculpta exhibiting significantly more anteroposterior humeral motion and protraction, and significantly less dorsoventral humeral motion and depression. Based on several intermediate kinematic parameters and angle of attack data, C. insculpta may in fact represent a synchronous rower or hybrid rower-flapper, suggesting that traditional views of C. insculpta as a flapper should be revised. PMID:23125335

  6. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) reduces urinary bladder damage during cyclophosphamide-induced cystitis in rats.

    PubMed

    Moraes, Janaína P; Pereira, Denyson S; Matos, Alexandre S; Santana, Danielle G; Santos, Cliomar A; Estevam, Charles S; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A

    2013-01-01

    Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100-400?mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx- were also evaluated. Treatment with EECp (100-400?mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx- induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100?mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400?mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

  7. The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

    PubMed Central

    Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

    2013-01-01

    Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400?mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx? were also evaluated. Treatment with EECp (100–400?mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx? induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100?mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400?mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

  8. Impaired ?-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

    PubMed Central

    Matsumoto, Takayuki; Szasz, Theodora; Tostes, Rita C.; Webb, R. Clinton

    2012-01-01

    ?-Adrenoceptor (?-AR)-mediated relaxation plays an important role in the regulation of vascular tone. ?-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that ?-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. ?-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of L-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel ? subunit was increased whereas the expression of BKCa channel ? subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKCa channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of ?-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired ?-AR-stimulated BKCa channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation. PMID:22388053

  9. Perinatal l -arginine and antioxidant supplements reduce adult blood pressure but not ameliorate the altered vascular function in spontaneously hypertensive rats

    Microsoft Academic Search

    Diego B. de Queiroz; Fernanda E. Ramos-Alves; Raphaella L. Fernandes; Cíntia P. Zuzu; Glória P. Duarte; Fabiano E. Xavier

    2010-01-01

    Spontaneously hypertensive rat (SHR) offspring from l-arginine- and antioxidant-supplemented SHR dams had persistent lower blood pressure in adulthood. We investigated the influence\\u000a of vascular mechanism in this effect. We analyzed response to acetylcholine and phenylephrine in aorta and superior mesenteric\\u000a arteries from Wistar–Kyoto (WKY), SHR, and SHR perinatally supplemented with l-arginine and 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl (TEMPOL; SHR-suppl). Supplements reduced blood pressure persistently

  10. Local cooling reduces skin ischemia under surface pressure in rats: an assessment by wavelet analysis of laser Doppler blood flow oscillations.

    PubMed

    Jan, Yih-Kuen; Lee, Bernard; Liao, Fuyuan; Foreman, Robert D

    2012-10-01

    The objectives of this study were to investigate the effects of local cooling on skin blood flow response to prolonged surface pressure and to identify associated physiological controls mediating these responses using the wavelet analysis of blood flow oscillations in rats. Twelve Sprague-Dawley rats were randomly assigned to three protocols, including pressure with local cooling (?t = -10 °C), pressure with local heating (?t = 10 °C) and pressure without temperature changes. Pressure of 700 mmHg was applied to the right trochanter area of rats for 3 h. Skin blood flow was measured using laser Doppler flowmetry. The 3 h loading period was divided into non-overlapping 30 min epochs for the analysis of the changes of skin blood flow oscillations using wavelet spectral analysis. The wavelet amplitudes and powers of three frequencies (metabolic, neurogenic and myogenic) of skin blood flow oscillations were calculated. The results showed that after an initial loading period of 30 min, skin blood flow continually decreased under the conditions of pressure with heating and of pressure without temperature changes, but maintained stable under the condition of pressure with cooling. Wavelet analysis revealed that stable skin blood flow under pressure with cooling was attributed to changes in the metabolic and myogenic frequencies. This study demonstrates that local cooling may be useful for reducing ischemia of weight-bearing soft tissues that prevents pressure ulcers. PMID:23010955

  11. Free fatty acid fractions from some vegetable oils exhibit reduced survival time-shortening activity in stroke-prone spontaneously hypertensive rats.

    PubMed

    Miyazaki, M; Huang, M Z; Takemura, N; Watanabe, S; Okuyama, H

    1998-07-01

    Previously, we demonstrated that several vegetable oils that included low-erucic rapeseed oil markedly shortened the survival time (by approximately 40%) of stroke-prone spontaneously hypertensive (SHRSP) rats as compared with perilla oil, soybean oil, and fish oil. We considered that a factor other than fatty acids is toxic to SHRSP rats, because the survival time-shortening activity could not be accounted for by the fatty acid compositions of these oils. In fact, a free fatty acid (FFA) fraction derived from lipase-treated rapeseed oil was found to be essentially devoid of such activity. A high-oleate safflower oil/safflower oil/perilla oil mixture exhibited a survival time-shortening activity comparable to that of rapeseed oil, but the activity of this mixed oil was also reduced by lipase treatment. A partially hydrogenated soybean oil shortened the survival time by approximately 40%, but a FFA fraction derived from lipase-treated partially hydrogenated soybean oil shortened it by 13% compared with soybean oil. Fatty acid compositions of the rapeseed oil and a FFA fraction derived from lipase-treated rapeseed oil were similar, but those of hepatic phospholipids of rats fed the oil and FFA were slightly but significantly different. These results support the interpretation that the survival time-shortening activity exhibited by some vegetable oils is due to minor components other than fatty acids, and that an active component(s) were produced in or contaminated soybean oil during the partial hydrogenation processes. PMID:9688167

  12. Cannabinoids attenuate norepinephrine-induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N-acetyltransferase activity without involvement of cannabinoid receptors.

    PubMed

    Koch, Marco; Dehghani, Faramarz; Habazettl, Iris; Schomerus, Christof; Korf, Horst-Werner

    2006-07-01

    Cannabinoids modulate neuronal and neuroendocrine circuits by binding to cannabinoid receptors acting upon cAMP/Ca(2+)-mediated intracellular signaling cascades. The rat pineal represents an established model to investigate intracellular signaling processes because a well defined input, the neurotransmitter norepinephrine, is transformed via cAMP/Ca(2+)-dependent mechanisms into an easily detectable output signal, the biosynthesis of melatonin. Here we investigated the impact of cannabinoids on norepinephrine-regulated melatonin biosynthesis in the rat pineal. We demonstrated that treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine-induced arylalkylamine N-acetyltransferase (AANAT) activity and melatonin biosynthesis. These effects were not mimicked by the cannabinoid receptor agonist WIN55,212-2 and were not blocked by cannabinoid 1 and 2 receptor antagonists. The cannabinoids used did not affect norepinephrine-induced increases in cAMP/Ca(2+) levels. Notably, cannabinoids were found to directly inhibit AANAT activity in lysates of the pineal gland. This effect was specific in so far as cannabinoids did not influence the activity of hydroxyindole-O-methyltransferase (HIOMT), the last enzyme in melatonin biosynthesis. Taken together, our data strongly suggest that cannabinoids inhibit AANAT activity and attenuate melatonin biosynthesis through intracellular actions without involvement of classical cannabinoid receptor-dependent signaling cascades. PMID:16805813

  13. Phaleria macrocarpa Boerl. (Thymelaeaceae) leaves increase SR-BI expression and reduce cholesterol levels in rats fed a high cholesterol diet.

    PubMed

    Andriani, Yosie; Tengku-Muhammad, Tengku Sifzizul; Mohamad, Habsah; Saidin, Jasnizat; Syamsumir, Desy Fitrya; Chew, Guat-Siew; Abdul Wahid, Mohd Effendy

    2015-01-01

    In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6) obtained from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats. PMID:25759957

  14. Plasticity associated changes in cortical somatosensory evoked potentials following spinal cord injury in rats.

    PubMed

    Bazley, Faith A; All, Angelo H; Thakor, Nitish V; Maybhate, Anil

    2011-01-01

    Spinal cord injury (SCI) causes a number of physiological and neurological changes resulting in loss of sensorimotor function. Recent work has shown that the central nervous system is capable of plastic behaviors post-injury, including axonal regrowth and cortical remapping. Functional integrity of afferent sensory pathways can be quantified using cortical somatosensory evoked potentials (SSEPs) recorded upon peripheral limb stimulation. We implanted 15 rats with transcranial screw electrodes and recorded SSEPs from cortical regions corresponding to each limb before and after a mild or moderate contusion injury. We report a post-injury increase in the mean amplitude of cortical SSEPs upon forelimb stimulation. SSEP amplitudes for mild and moderate SCI groups increased by 183% ± 95% and 107% ± 38% over baseline, respectively, while hindlimb SSEPs decreased by 58% ± 14% and 79% ± 4%. In addition, we report increased SSEP amplitude measured from the anatomically adjacent hindlimb region upon forelimb stimulation (increase of 90% ± 19%). Our results show that previously allocated hindlimb cortical regions are now activated by forelimb stimulation, suggesting an expansion in the area of cortical forelimb representation into hindlimb regions after an injury. This result is indicative of adaptive plasticity in undamaged areas of the CNS following SCI. PMID:22254728

  15. Local group I mGluR antagonists reduce TMJ-evoked activity of trigeminal subnucleus caudalis neurons in female rats.

    PubMed

    Tashiro, A; Nishida, Y; Bereiter, D A

    2015-07-23

    Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are functionally linked to estrogen receptors and play a key role in the plasticity of central neurons. Estrogen status strongly influences sensory input from the temporomandibular joint (TMJ) to neurons at the spinomedullary (Vc/C1-2) region. This study tested the hypothesis that TMJ input to trigeminal subnucleus caudalis/upper cervical cord (Vc/C1-2) neurons involved group I mGluR activation and depended on estrogen status. TMJ-responsive neurons were recorded in superficial laminae at the Vc/C1-2 region in ovariectomized (OvX) female rats treated with low-dose estradiol (2?g/day, LE) or high-dose estradiol (20?g/day, HE) for 2days. TMJ-responsive units were activated by adenosine triphosphate (ATP, 1mM) injected into the joint space. Receptor antagonists selective for mGluR1 (CPCCOEt) or mGluR5 (MPEP) were applied topically to the Vc/C1-2 surface at the site of recording 10min prior to the intra-TMJ ATP stimulus. In HE rats, CPCCOEt (50 and 500?M) markedly reduced ATP-evoked unit activity. By contrast, in LE rats, a small but significant increase in neural activity was seen after 50?M CPCCOEt, while 500?M caused a large reduction in activity that was similar in magnitude as that seen in HE rats. Local application of MPEP produced a significant inhibition of TMJ-evoked unit activity independent of estrogen status. Neither mGluR1 nor mGluR5 antagonism altered the spontaneous activity of TMJ units in HE or LE rats. High-dose MPEP caused a small reduction in the size of the convergent cutaneous receptive field in HE rats, while CPCCOEt had no effect. These data suggest that group I mGluRs play a key role in sensory integration of TMJ nociceptive input to the Vc/C1-2 region and are largely independent of estrogen status. PMID:25934040

  16. Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats.

    PubMed

    Erfanian, Arezoo; Mirhosseini, Hamed; Rasti, Babak; Hair-Bejo, Mohd; Mustafa, Shuhaimi Bin; Manap, Mohd Yazid Abd

    2015-06-24

    The aim of this study was to evaluate the effects of fortification and nano-size reduction on calcium absorption and bioavailability of milk powder formula in sham, ovariectomized, and ovariectomized-osteoporosis rats as a menopause and menopause-osteoporosis model. Skim milk powder and skim milk powder fortified with calcium citrate and the suitable doses of inulin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamins D3, K1, and B6 were formulated based on the North American and Western European recommended dietary allowances. Optimization on cycle and pressure of high-pressure homogenizer was done to produce nano-fortified milk powder. In vivo study demonstrated that fortification and calcium citrate nano-fortified milk powder increased absorption and bioavailability of calcium, as well as bone stiffness and bone strength in sham, ovariectomized, and ovariectomized-osteoporosis rats. This study successfully developed an effective fortified milk powder for food application. PMID:26022498

  17. Reduced effectiveness of escitalopram in the forced swimming test is associated with increased serotonin clearance rate in food restricted rats

    PubMed Central

    France, CP; Li, J-X; Owens, WA; Koek, W; Toney, GM; Daws, LC

    2012-01-01

    Efficacy of antidepressant drugs is often limited. One of the limiting factors may be diet. This study shows that the effect of escitalopram in the forced swimming test is diminished in rats by food restriction that decreased body weight by 8%. The primary target for escitalopram is the serotonin (5-HT) transporter. Using high-speed chronoamperometry to measure 5-HT clearance in vivo in rats fed the same food restricted diet, the rate of 5-HT clearance from extracellular fluid in brain was dramatically increased. Increased 5-HT transporter function under conditions of dietary restriction might contribute to the decreased effect of escitalopram. These results suggest that diet plays an integral role in determining efficacy of antidepressant drugs, and might well generalize to other psychoactive drugs that impinge upon the 5-HT transporter. PMID:19419596

  18. (2R,3S)-Pinobanksin-3-cinnamate improves cognition and reduces oxidative stress in rats with vascular dementia.

    PubMed

    Liu, Hong; Zhao, Min; Yang, Shen; Gong, Dian-Rong; Chen, De-Zhe; Du, De-Yong

    2015-07-01

    This study investigated the neuroprotective effects of (2R,3S)-pinobanksin-3-cinnamate (PNC) in rats with occlusion-damaged bilateral common carotid arteries. Administration with PNC (5 and 10 mg/kg/day) for 5 weeks significantly improved the behavioral performance of rats with vascular dementia, as showed in the Morris water maze test by shortening the escape latency and latency of crossing, completing more platform crossings, as well as spending more time in the target zone. Further evaluations found that PNC could markedly decrease malondialdehyde levels, enhance superoxide dismutase activity and glutathione levels, and decrease the release of cytochrome c as well as the activities of caspases. Moreover, PNC increased Nrf2 and anti-apoptotic bcl-2 protein expression, while Nox1 and pro-apopotic bax protein expression was