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1

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

PubMed

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

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

2014-05-15

2

Sensory feedback alters spontaneous limb movements in newborn rats: effects of unilateral forelimb weighting  

PubMed Central

Perinatal mammals show spontaneous movements that often appear random and uncoordinated. Here we examined if spontaneous limb movements are responsive to a proprioceptive manipulation by applying a weight unilaterally to a forelimb of postnatal day 0 (P0; day of birth) and P1 rats. Weights were calibrated to approximate 0%, 25%, 50% or 100% of the average mass of a forelimb, and were attached at the wrist. P0 and P1 pups showed different levels of activity during the period of limb weighting, in response to weight removal, and during the period after weighting. Pups exposed to 50% and 100% weights showed proportionately more activity in the nonweighted forelimb during the period of weighting, suggesting a threshold for evoking proprioceptive changes. Findings suggest that newborn rats use movement-related feedback to modulate spontaneous motor activity, and corroborate studies of human infants that have suggested a role for proprioception during early motor development.

Brumley, Michele R.; Robinson, Scott R.

2012-01-01

3

Large cortical lesions produce enduring forelimb placing deficits in un-treated rats and treatment with NMDA antagonists or anti-oxidant drugs induces behavioral recovery.  

PubMed

Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl(2)), or the anti-oxidant N-tert-butyl-alpha-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats. PMID:11044594

Hoane, M R; Barbay, S; Barth, T M

2000-09-15

4

Differences in acquisition and full performance in skilled forelimb use as measured by the `staircase test' in five rat strains  

Microsoft Academic Search

Skilled forelimb use was examined in five different rat strains (DA\\/Ztm, LEW\\/Ztm-ci, LEW.1W\\/Ztm, SD\\/Ztm, SPRD\\/Ztm-Cu3) by means of the `staircase test', as originally described by Montoya et al. [20](C.P. Montoya, H.L. Campbell, K.D. Pemberton, S.B. Dunnett, The `staircase test': A measure of independent forelimb reaching and grasping abilities in rats, J. Neurosci. Methods 36 (1991) 219–228). Strain-dependent differences were observed

Guido Nikkhah; Christoph Rosenthal; Hans-Jürgen Hedrich; Madjid Samii

1998-01-01

5

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

NASA Astrophysics Data System (ADS)

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.

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

2011-06-01

6

Encoding of forelimb forces by corticospinal tract activity in the rat.  

PubMed

In search of a solution to the long standing problems encountered in traditional brain computer interfaces (BCI), the lateral descending tracts of the spinal cord present an alternative site for taping into the volitional motor signals. Due to the convergence of the cortical outputs into a final common pathway in the descending tracts of the spinal cord, neural interfaces with the spinal cord can potentially acquire signals richer with volitional information in a smaller anatomical region. The main objective of this study was to evaluate the feasibility of extracting motor control signals from the corticospinal tract (CST) of the rat spinal cord. Flexible substrate, multi-electrode arrays (MEA) were implanted in the CST of rats trained for a lever pressing task. This novel use of flexible substrate MEAs allowed recording of CST activity in behaving animals for up to three weeks with the current implantation technique. Time-frequency and principal component analyses (PCA) were applied to the neural signals to reconstruct isometric forelimb forces. Computed regression coefficients were then used to predict isometric forces in additional trials. The correlation between measured and predicted forces in the vertical direction averaged across six animals was 0.67 and R (2) value was 0.44. Force regression in the horizontal directions was less successful, possibly due to the small amplitude of forces. Neural signals above and near the high gamma band made the largest contributions to prediction of forces. The results of this study support the feasibility of a spinal cord computer interface (SCCI) for generation of command signals in paralyzed individuals. PMID:24847198

Guo, Yi; Foulds, Richard A; Adamovich, Sergei V; Sahin, Mesut

2014-01-01

7

Encoding of forelimb forces by corticospinal tract activity in the rat  

PubMed Central

In search of a solution to the long standing problems encountered in traditional brain computer interfaces (BCI), the lateral descending tracts of the spinal cord present an alternative site for taping into the volitional motor signals. Due to the convergence of the cortical outputs into a final common pathway in the descending tracts of the spinal cord, neural interfaces with the spinal cord can potentially acquire signals richer with volitional information in a smaller anatomical region. The main objective of this study was to evaluate the feasibility of extracting motor control signals from the corticospinal tract (CST) of the rat spinal cord. Flexible substrate, multi-electrode arrays (MEA) were implanted in the CST of rats trained for a lever pressing task. This novel use of flexible substrate MEAs allowed recording of CST activity in behaving animals for up to three weeks with the current implantation technique. Time-frequency and principal component analyses (PCA) were applied to the neural signals to reconstruct isometric forelimb forces. Computed regression coefficients were then used to predict isometric forces in additional trials. The correlation between measured and predicted forces in the vertical direction averaged across six animals was 0.67 and R2 value was 0.44. Force regression in the horizontal directions was less successful, possibly due to the small amplitude of forces. Neural signals above and near the high gamma band made the largest contributions to prediction of forces. The results of this study support the feasibility of a spinal cord computer interface (SCCI) for generation of command signals in paralyzed individuals.

Guo, Yi; Foulds, Richard A.; Adamovich, Sergei V.; Sahin, Mesut

2014-01-01

8

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

PubMed Central

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.

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

2013-01-01

9

Forelimb EMG-based trigger to control an electronic spinal bridge to enable hindlimb stepping after a complete spinal cord lesion in rats  

PubMed Central

Background A complete spinal cord transection results in loss of all supraspinal motor control below the level of the injury. The neural circuitry in the lumbosacral spinal cord, however, can generate locomotor patterns in the hindlimbs of rats and cats with the aid of motor training, epidural stimulation and/or administration of monoaminergic agonists. We hypothesized that there are patterns of EMG signals from the forelimbs during quadrupedal locomotion that uniquely represent a signal for the “intent” to step with the hindlimbs. These observations led us to determine whether this type of “indirect” volitional control of stepping can be achieved after a complete spinal cord injury. The objective of this study was to develop an electronic bridge across the lesion of the spinal cord to facilitate hindlimb stepping after a complete mid-thoracic spinal cord injury in adult rats. Methods We developed an electronic spinal bridge that can detect specific patterns of EMG activity from the forelimb muscles to initiate electrical-enabling motor control (eEmc) of the lumbosacral spinal cord to enable quadrupedal stepping after a complete spinal cord transection in rats. A moving window detection algorithm was implemented in a small microprocessor to detect biceps brachii EMG activity bilaterally that then was used to initiate and terminate epidural stimulation in the lumbosacral spinal cord. We found dominant frequencies of 180–220 Hz in the EMG of the forelimb muscles during active periods, whereas these frequencies were between 0–10 Hz when the muscles were inactive. Results and conclusions Once the algorithm was validated to represent kinematically appropriate quadrupedal stepping, we observed that the algorithm could reliably detect, initiate, and facilitate stepping under different pharmacological conditions and at various treadmill speeds.

2012-01-01

10

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

PubMed Central

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.

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

2009-01-01

11

Fos Immunoreactivity and NADPH-d Reactivity in the Brain Cortex of Rats Realizing Motivated Stereotyped Movements by the Forelimb  

Microsoft Academic Search

A comparative study of mmunoreactivity with respect to c-Fos protein in the motor (zones ?1 and ?2), medial prefrontal (PrL and IL), and cingular (Cg1 and Cg2) cortices allowed us to find significant differences between the intensities of expression of gene c-fos in these cortical regions in control rats (group 1) and animals trained to perform catching of food globules

O. V. Vlasenko; A. I. Pilyavskii; V. A. Maiskii; A. V. Maznichenko

2008-01-01

12

Does treatment with bone marrow mononuclear cells recover skilled motor function after focal cortical ischemia? Analysis with a forelimb skilled motor task in rats.  

PubMed

Previous studies have shown sensorimotor recovery by treatment with bone marrow mononuclear cells (BMMCs) after focal brain ischemia. However, sensorimotor tests commonly used are designed to examine motor patterns that do not involve skill or training. We evaluated whether BMMCs treatment was able to recover forelimb skilled movements. Reaching chamber/pellet retrieval (RCPR) task was used, in which animals had to learn to grasp a single food pellet and lead it to its mouth. We also evaluated therapeutic effect of this training on unskilled sensorimotor function. Adult male Wistar rats suffered unilateral cortical ischemia by thermocoagulation in motor and somesthetic primary areas. A day later, they received i.v. injection of 3×10(7) BMMCs or vehicle (saline), forming four experimental groups: BMMCs+RCPR; saline+RCPR; BMMCs and saline. Cylinder and adhesive tests were applied in all experimental groups, and all behavioral tests were performed before and along post-ischemic weeks after induction of ischemia. Results from RCPR task showed no significant difference between BMMCs+RCPR and saline+RCPR groups. In cylinder test, BMMCs-treated groups showed significant recovery, but no significant effect of RCPR training was observed. In adhesive test, BMMCs treatment promoted significant recovery. Synergistic effect was found since only together they were able to accelerate recovery. The results showed that BMMCs treatment promoted increased recovery of unsophisticated sensorimotor function, but not of skilled forepaw movements. Thus, BMMCs might not be able to recover all aspects of sensorimotor functions, although further studies are still needed to investigate this treatment in ischemic lesions with different locations and extensions. PMID:23178695

de Fátima Dos Santos Sampaio, Maria; Marcilio, Fralini Dos Santos; Giraldi-Guimarães, Arthur

2013-01-25

13

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

PubMed

Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. PMID:23954448

Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

2013-12-01

14

Functional organization of vestibular and visual inputs to neck and forelimb motoneurons in the frog.  

PubMed

1. Intracellular responses in neck and forelimb motoneurons to electrical stimulation of the vestibular nerve, the optic tectum, and the optic nerve were studied in frog. 2. Stimulation of the anterior branch of the vestibular nerve typically produced EPSPs, bilaterally, in neck, shoulder (DOR), and forelimb extensor (TRI, RAD) motoneurons, and bilateral IPSPs in forelimb adductor (PED) and flexor (ULN, COR) motoneurons. 3. Latencies of PSPs recorded in neck, shoulder, and proximal extensor motoneurons (TRI) were mostly in the disynaptic range, whereas many of those recorded in distal extensor (RAD) and in adductor and flexor motoneurons involved three synapses. 4. Lesion of the vestibulospinal fibers greatly reduced the vestibular nerve-evoked field potentials in the spinal cord and the occurrence of PSPs in forelimb motoneurons. These results as well as the latency measurements suggest that the pathway linking vestibular nerve and forelimb motoneurons mainly consists of vestibulospinal fibers, though involvement of other structures for production of later PSPs could not be completely ruled out. Hemisection of the brain stem at its most caudal level showed that the pathway to the contralateral motoneurons crosses at the level of brain stem as well as in the spinal cord. 5. Stimulation of the optic tectum produced EPSPs, IPSPs, and a mixture of EPSPs and IPSPs in neck, shoulder, and forelimb motoneurons, bilaterally. Most frequently, a combination of an excitation and inhibition was observed. The pathway from the optic tectum to neck and limb motoneurons is at least dysnaptic in nature. 6. Stimulation of the optic nerve produced IPSPs and a mixture of EPSPs and IPSPs in neck and forelimb motoneurons. Impulses originating from the optic nerve descend as far as to lumbar motoneurons producing EPSP-IPSP sequences bilaterally. 7. Interaction studies suggested that the vestibular and optic pathways to neck and forelimb motoneurons are separate from each other so that the site of integration of vestibular and visual input occurs at the level of motoneurons. 8. Evidence for electronic coupling among forelimb motoneurons and electrical synaptic transmission in th pathway linking vestibular nerve and forelimb motoneurons is presented. PMID:191572

Maeda, M; Magherini, P C; Precht, W

1977-03-01

15

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

PubMed

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

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

2008-02-01

16

Neuromuscular anatomy and evolution of the cetacean forelimb.  

PubMed

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

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

2007-09-01

17

Altered developmental events in the anterior region of the chick forelimb give rise to avian-specific digit loss.  

PubMed

Background: Avian forelimb (wing) contains only three digits, and the three-digit formation in the bird forelimb is one of the avian-specific limb characteristics that have been evolutionarily inherited from the common ancestral form in dinosaurs. Despite many studies on digit formation in the chick limb bud, the developmental mechanisms giving rise to the three-digit forelimb in birds have not been completely clarified. Results: To identify which cell populations of the early limb bud contribute to digit formation in the late limb bud, fate maps of the early fore- and hindlimb buds were prepared. Based on these fate maps, we found that the digit-forming region in the forelimb bud is narrower than that in the hindlimb bud, suggesting that some developmental mechanisms on the anterior-most region lead to a reduced number of digits in the forelimb. We also found temporal differences in the onset of appearance of the ANZ (anterior necrotic zone) as well as differences in the position of the anterior edge of the AER. Conclusions: Forelimb-specific events in the anterior limb bud are possible developmental mechanisms that might generate the different cell fates in the fore- and hindlimb buds, regulating the number of digits in birds. Developmental Dynamics 243:741-752, 2014. © 2014 Wiley Periodicals, Inc. PMID:24616028

Nomura, Naoki; Yokoyama, Hitoshi; Tamura, Koji

2014-06-01

18

Ivermectin reduces sexual behavior in female rats.  

PubMed

Ivermectin (IVM) is an antiparasitic drug that is widely used in domestic animals. In mammals, IVM acts as a ?-aminobutyric acid (GABA) receptor agonist. This neurotransmitter plays an important role in the regulation of female sexual behavior. The present study investigated the effects of therapeutic (0.2 mg/kg) and high (1.0 mg/kg) IVM doses on female sexual behavior in physiological and pharmacological conditions. Female rats in estrus or treated with estradiol valerate to induce sexual behavior 24 h before the experiments were used. Ivermectin was administered 15 min before the sexual observations. The number of lordosis events in 10 mounts was recorded to calculate the lordosis quotient. The intensity of lordosis (0 [no lordosis], 1 [low lordosis], 2 [normal lordosis] and 3 [exaggerated lordosis]) was scored. In estrus and hormonal treated female rats, both IVM doses decreased the intensity of the lordosis reflex and the percentage of females that presented high levels of lordosis (exaggerated lordosis). However, the number of females that presented lordosis was unaltered. We conclude that in both hormonal conditions, 0.2mg/kg IVM treatment reduced female sexual behavior and the execution of the lordosis reflex. The present results may be useful for avoiding the side effects of this drug in veterinary practice. PMID:24681284

Moreira, N; Bernardi, M M; Spinosa, H S

2014-01-01

19

Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study  

Microsoft Academic Search

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on

Ni Xie; Qiuhong Yang; Tyson D. Chappell; Cheng-Xiang Li; Robert S. Waters

2010-01-01

20

The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs  

PubMed Central

Summary The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.

Yamamoto, Mako; Matsuzaki, Tomoko; Takahashi, Rei; Adachi, Eijiro; Maeda, Yasuhiro; Yamaguchi, Sachiyo; Kitayama, Hitoshi; Echizenya, Michiko; Morioka, Yoko; Alexander, David B.; Yagi, Takeshi; Itohara, Shigeyoshi; Nakamura, Takashi; Akiyama, Haruhiko; Noda, Makoto

2012-01-01

21

In vivo optogenetic tracing of functional corticocortical connections between motor forelimb areas  

PubMed Central

Interactions between distinct motor cortical areas are essential for coordinated motor behaviors. In rodents, the motor cortical forelimb areas are divided into at least two distinct areas: the rostral forelimb area (RFA) and the caudal forelimb area (CFA). The RFA is thought to be an equivalent of the premotor cortex (PM) in primates, whereas the CFA is believed to be an equivalent of the primary motor cortex. Although reciprocal connections between the RFA and the CFA have been anatomically identified in rats, it is unknown whether there are functional connections between these areas that can induce postsynaptic spikes. In this study, we used an in vivo Channelrhodopsin-2 (ChR2) photostimulation method to trace the functional connections between the mouse RFA and CFA. Simultaneous electrical recordings were utilized to detect spiking activities induced by synaptic inputs originating from photostimulated areas. This method, in combination with anatomical tracing, demonstrated that the RFA receives strong functional projections from layer 2/3 and/or layer 5a, but not from layer 5b (L5b), of the CFA. Further, the CFA receives strong projections from L5b neurons of the RFA. The onset latency of electrical responses evoked in remote areas upon photostimulation of the other areas was approximately 10 ms, which is consistent with the synaptic connectivity between these areas. Our results suggest that neuronal activities in the RFA and the CFA during movements are formed through asymmetric reciprocal connections.

Hira, Riichiro; Ohkubo, Fuki; Tanaka, Yasuhiro R.; Masamizu, Yoshito; Augustine, George J.; Kasai, Haruo; Matsuzaki, Masanori

2013-01-01

22

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

PubMed Central

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.

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

23

Dimensions of forelimb muscles in orangutans and chimpanzees  

PubMed Central

Eight forelimbs of three orangutans and four chimpanzees were dissected and the muscle mass, fascicle length and physiological cross-sectional area (PCSA) of all forelimb muscles were systematically recorded to explore possible interspecies variation in muscle dimensions. Muscle mass and PCSA were divided by the total mass and total PCSA of the entire forelimb muscles for normalization. The results indicate that the mass and PCSA ratios of the monoarticular elbow flexors (M. brachialisand M. brachioradialis) are significantly larger in orangutans. In contrast, the mass ratios of the biarticular muscles in the upper arm (the short head of M. biceps brachiiand the long head of M. triceps brachii) are significantly larger in chimpanzees. For the rotator cuff muscles, the force-generating capacity of M. subscapularisis significantly larger in orangutans, whereas the opposite rotator cuff muscle, M. infraspinatus, is larger in chimpanzees. These differences in forelimb muscle dimensions of the two species may reflect functional specialization for their different positional and locomotor behaviors.

Oishi, Motoharu; Ogihara, Naomichi; Endo, Hideki; Ichihara, Nobutsune; Asari, Masao

2009-01-01

24

Evolutionary Morphology of the Tenrecoidea (Mammalia) Forelimb Skeleton  

Microsoft Academic Search

Functional morphology of the mammalian forelimb skeleton and the details of its joints have been explored and discussed in\\u000a great depth relative to other postcranial regions, despite potential difficulties with interpreting the morphology of this\\u000a region. The mammalian forelimb performs a variety of biological roles, including postural, locomotor, feeding, exploratory,\\u000a grooming, and defense related behaviors. Detailed morphology might therefore reflect

Justine A. Salton; Eric J. Sargis

25

Exercise induces cortical plasticity after neonatal spinal cord injury in the rat  

PubMed Central

Exercise-induced cortical plasticity is associated with improved functional outcome after brain or nerve injury. Exercise also improves functional outcomes after spinal cord injury, but its effects on cortical plasticity are not known. The goal of this investigation was to study the effect of moderate exercise (treadmill locomotion, 3 min/day, 5days/week) on the somatotopic organization of forelimb and hindlimb somatosensory cortex (SI) after neonatal thoracic transection. We used adult rats spinalized as neonates because some of these animals develop weight-supported stepping and, therefore, the relationship between cortical plasticity and stepping could also be examined. Acute, single-neuron mapping was used to determine the percentage of cortical cells responding to cutaneous forelimb stimulation in normal, spinalized, and exercised spinalized rats. Multiple single neuron recording from arrays of chronically implanted microwires examined the magnitude of response of these cells in normal and exercised spinalized rats. Our results show that exercise not only increased the percentage of responding cells in the hindlimb SI, but also increased the magnitude of the response of these cells. This increase in response magnitude was correlated with behavioral outcome measures. In the forelimb SI, neonatal transection reduced the percentage of responding cells to forelimb stimulation but exercise reversed this loss. This restoration in the percentage of responding cells after exercise was accompanied by an increase in their response magnitude. Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI.

Kao, T; Shumsky, JS; Murray, M; Moxon, KA

2009-01-01

26

The dorsomedial frontal cortex: eye and forelimb fields.  

PubMed

This review yields three conclusions: first, the eye field as described using unit recording and electrical stimulation on behaving monkeys trained to fixate visual targets is much larger than the 4 mm2 area originally described. Second, the eye field and forelimb field share a similar neural space within the dorsomedial frontal cortex (DMFC); thus the electrophysiogical studies that have been conducted on visually guided and sensory-triggered forelimb movements must be re-evaluated, since none of these studies controlled eye movement and eye position independently. Third, a topographic map representing eye position in orbit has been discovered in the DMFC; it is proposed that this topographic map records the order of positions of the eyes and forelimbs during the acquisition of visually guided movement sequences. PMID:7779289

Tehovnik, E J

1995-03-01

27

Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats  

PubMed Central

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the ?-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through ?-adrenergic descending inhibitory systems at the spinal level.

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

2011-01-01

28

Red maca (Lepidium meyenii) reduced prostate size in rats  

PubMed Central

Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions Red Maca, a cruciferous plant from the highland of Peru, reduced ventral prostate size in normal and TE treated rats.

Gonzales, Gustavo F; Miranda, Sara; Nieto, Jessica; Fernandez, Gilma; Yucra, Sandra; Rubio, Julio; Yi, Pedro; Gasco, Manuel

2005-01-01

29

Dimensions of forelimb muscles in orangutans and chimpanzees.  

PubMed

Eight forelimbs of three orangutans and four chimpanzees were dissected and the muscle mass, fascicle length and physiological cross-sectional area (PCSA) of all forelimb muscles were systematically recorded to explore possible interspecies variation in muscle dimensions. Muscle mass and PCSA were divided by the total mass and total PCSA of the entire forelimb muscles for normalization. The results indicate that the mass and PCSA ratios of the monoarticular elbow flexors (M. brachialis and M. brachioradialis) are significantly larger in orangutans. In contrast, the mass ratios of the biarticular muscles in the upper arm (the short head of M. biceps brachii and the long head of M. triceps brachii) are significantly larger in chimpanzees. For the rotator cuff muscles, the force-generating capacity of M. subscapularis is significantly larger in orangutans, whereas the opposite rotator cuff muscle, M. infraspinatus, is larger in chimpanzees. These differences in forelimb muscle dimensions of the two species may reflect functional specialization for their different positional and locomotor behaviors. PMID:19619166

Oishi, Motoharu; Ogihara, Naomichi; Endo, Hideki; Ichihara, Nobutsune; Asari, Masao

2009-10-01

30

Forelimb skeletal morphology and flight mode evolution in pelecaniform birds  

Microsoft Academic Search

The total length and mid-shaft diameters of wing elements of 50 species of pelecaniform birds were examined to investigate how forelimb skeletal morphology varies with body size and flight mode within this group. Pelecaniforms were assigned to flight mode categories based on primary habitual behaviors (soar, flap–glide, continuous flap). Allometric and discriminant function analyses were conducted on wing element variables

Erin L. R. Simons

2010-01-01

31

Hypertonic saline solution reduces the inflammatory response in endotoxemic rats  

PubMed Central

OBJECTIVE: Volume replacement in septic patients improves hemodynamic stability. This effect can reduce the inflammatory response. The objective of this study was to evaluate the effect of 7.5% hypertonic saline solution versus 0.9% normal saline solution for volume replacement during an inflammatory response in endotoxemic rats. METHODS: We measured cytokines (serum and gut), nitrite, and lipid peroxidation (TBARS) as indicators of oxidative stress in the gut. Rats were divided into four groups: control group (C) that did not receive lipopolysaccharide; lipopolysaccharide injection without treatment (LPS); lipopolysaccharide injection with saline treatment (LPS +S); and lipopolysaccharide injection with hypertonic saline treatment (LPS +H). Serum and intestine were collected. Measurements were taken at 1.5, 8, and 24 h after lipopolysaccharide administration. RESULTS: Of the four groups, the LPS +H group had the highest survival rate. Hypertonic saline solution treatment led to lower levels of IL-6, IL-10, nitric oxide, and thiobarbituric acid reactive substances compared to 0.9% normal saline. In addition, hypertonic saline treatment resulted in a lower mortality compared to 0.9% normal saline treatment in endotoxemic rats. Volume replacement reduced levels of inflammatory mediators in the plasma and gut. CONCLUSION: Hypertonic saline treatment reduced mortality and lowered levels of inflammatory mediators in endotoxemic rats. Hypertonic saline also has the advantage of requiring less volume replacement.

Theobaldo, Mariana Cardillo; Barbeiro, Hermes Vieira; Barbeiro, Denise Frediani; Petroni, Ricardo; Soriano, Francisco Garcia

2012-01-01

32

The timing and amount of vagus nerve stimulation during rehabilitative training affect poststroke recovery of forelimb strength.  

PubMed

Loss of upper arm strength after stroke is a leading cause of disability. Strategies that can enhance the benefits of rehabilitative training could improve motor function after stroke. Recent studies in a rat model of ischemic stroke have demonstrated that vagus nerve stimulation (VNS) paired with rehabilitative training substantially improves recovery of forelimb strength compared with extensive rehabilitative training without VNS. Here we report that the timing and amount of stimulation affect the degree of forelimb strength recovery. Similar amounts of Delayed VNS delivered 2 h after daily rehabilitative training sessions resulted in significantly less improvement compared with that on delivery of VNS that is paired with identical rehabilitative training. Significantly less recovery also occurred when several-fold more VNS was delivered during rehabilitative training. Both delayed and additional VNS confer moderately improved recovery compared with extensive rehabilitative training without VNS, but fail to enhance recovery to the same degree as VNS that is timed to occur with successful movements. These findings confirm that VNS paired with rehabilitative training holds promise for restoring forelimb strength poststroke and indicate that both the timing and the amount of VNS should be optimized to maximize therapeutic benefits. PMID:24818637

Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Sloan, Andrew M; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

2014-06-18

33

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

PubMed Central

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.

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

2012-01-01

34

Sepiapterin reduces postischemic injury in the rat heart  

Microsoft Academic Search

A reduced availability of tetrahydrobiopterin (BH4), an essential cofactor for NO-synthesis, is causally involved in the development of endothelial dysfunction associated with ischemia\\/reperfusion. We, therefore, investigated the effect of sepiapterin, a substrate for BH4 synthesis, on postischemic injury in myocardial infarction and myocardial stunning. In rats, myocardial stunning was induced by repetitive ischemia (5×10-min ligature of the left coronary artery,

Christiane P. Tiefenbacher; Ching-Hua Lee; Jolanthe Kapitza; Volker Dietz; Feraydoon Niroomand

2003-01-01

35

Astaxanthin reduces ischemic brain injury in adult rats  

PubMed Central

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

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

2009-01-01

36

Anatomical, Architectural, and Biochemical Diversity of the Murine Forelimb Muscles  

PubMed Central

Summary We characterized the architecture, fiber type, titin isoform distribution, and collagen content of 27 portions of 22 muscles in the murine forelimb. The mouse thoracic limb was different from the human arm in that it had the extensor digitorum lateralis muscle and no brachioradialis muscle. Architecturally, the mouse forelimb differed from humans with regard to load bearing, having a much larger contribution from extensors than flexors. In mice, the extensor:flexor PCSA ratio is 2.7 while in humans it is only 1.4. When the architectural difference index was calculated, similarities became especially apparent between flexors and extensors of the distal thoracic limb, as well pronators. Discriminant analysis revealed that biochemical measures of collagen, titin, and myosin heavy chain were all strong between-species discriminators. In terms of composition, when compared to similar muscles in humans, mice had, on average, faster muscles with higher collagen content and larger titin isoforms. This report establishes the anatomical and biochemical properties of mouse forelimb muscles. Given the prevalence of this species in biological studies, these data will be invaluable for studying the biological basis of mouse muscle structure and function.

Mathewson, Margie A.; Chapman, Mark A.; Hentzen, Eric R.; Friden, Jan; Lieber, Richard L.

2014-01-01

37

Perindopril May Improve the Hippocampal Reduced Glutathione Content in Rats  

PubMed Central

Purpose: Oxidative stress and renin- angiotensin system are both involved in the pathophysiology of most of the systemic and central disorders as well as in aging. Angiotensin converting enzyme (ACE) inhibitors, well known for their cardiovascular beneficial effects, have also shown antioxidant properties in pathologic conditions. This study aimed to evaluate the central effect of ACE inhibitors on oxidative status under no pathologic condition. Methods: Adult male rats were divided into four groups of 9 rats each. Groups were treated orally by perindopril at the doses of 1, 2, 4 mg/kg/day or normal saline as the control for four consecutive weeks. At the end of the treatment period the reduced and oxidized glutathione (GSH and GSSG respectively) and malondialdehyde (MDA), the product of lipid peroxidation, were measured in the rats’ hippocampus. Results: The GSH increased dose dependently and was significantly higher in the 2 mg/kg perindopril treated group than the control group (p<0.05) while the GSSG level remained unchanged. As a consequent, the ratio of GSH to GSSG increased significantly in a dose dependent manner. There was not any significant change in MDA. Conclusion: This study demonstrated that ACE inhibition may cause an increase in GSH as an anti- oxidant defense in the hippocampus.

Mashhoody, Tahereh; Rastegar, Karim; Zal, Fatemeh

2014-01-01

38

Perindopril may improve the hippocampal reduced glutathione content in rats.  

PubMed

Purpose: Oxidative stress and renin- angiotensin system are both involved in the pathophysiology of most of the systemic and central disorders as well as in aging. Angiotensin converting enzyme (ACE) inhibitors, well known for their cardiovascular beneficial effects, have also shown antioxidant properties in pathologic conditions. This study aimed to evaluate the central effect of ACE inhibitors on oxidative status under no pathologic condition. Methods: Adult male rats were divided into four groups of 9 rats each. Groups were treated orally by perindopril at the doses of 1, 2, 4 mg/kg/day or normal saline as the control for four consecutive weeks. At the end of the treatment period the reduced and oxidized glutathione (GSH and GSSG respectively) and malondialdehyde (MDA), the product of lipid peroxidation, were measured in the rats' hippocampus. Results: The GSH increased dose dependently and was significantly higher in the 2 mg/kg perindopril treated group than the control group (p<0.05) while the GSSG level remained unchanged. As a consequent, the ratio of GSH to GSSG increased significantly in a dose dependent manner. There was not any significant change in MDA. Conclusion: This study demonstrated that ACE inhibition may cause an increase in GSH as an anti- oxidant defense in the hippocampus. PMID:24511479

Mashhoody, Tahereh; Rastegar, Karim; Zal, Fatemeh

2014-01-01

39

Azithromycin reduces inflammation in a rat model of acute conjunctivitis  

PubMed Central

Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-?, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.

Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduna, Maite; Garcia-Garcia, Laura; Zarranz-Ventura, Javier; Garcia-Layana, Alfredo

2013-01-01

40

Functional anatomy of the cheetah (Acinonyx jubatus) forelimb  

PubMed Central

Despite the cheetah being the fastest living land mammal, we know remarkably little about how it attains such high top speeds (29 m s?1). Here we aim to describe and quantify the musculoskeletal anatomy of the cheetah forelimb and compare it to the racing greyhound, an animal of similar mass, but which can only attain a top speed of 17 m s?1. Measurements were made of muscle mass, fascicle length and moment arms, enabling calculations of muscle volume, physiological cross-sectional area (PCSA), and estimates of joint torques and rotational velocities. Bone lengths, masses and mid-shaft cross-sectional areas were also measured. Several species differences were observed and have been discussed, such as the long fibred serratus ventralis muscle in the cheetah, which we theorise may translate the scapula along the rib cage (as has been observed in domestic cats), thereby increasing the cheetah's effective limb length. The cheetah's proximal limb contained many large PCSA muscles with long moment arms, suggesting that this limb is resisting large ground reaction force joint torques and therefore is not functioning as a simple strut. Its structure may also reflect a need for control and stabilisation during the high-speed manoeuvring in hunting. The large digital flexors and extensors observed in the cheetah forelimb may be used to dig the digits into the ground, aiding with traction when galloping and manoeuvring.

Hudson, Penny E; Corr, Sandra A; Payne-Davis, Rachel C; Clancy, Sinead N; Lane, Emily; Wilson, Alan M

2011-01-01

41

Functional anatomy of the cheetah (Acinonyx jubatus) forelimb.  

PubMed

Despite the cheetah being the fastest living land mammal, we know remarkably little about how it attains such high top speeds (29 m s(-1)). Here we aim to describe and quantify the musculoskeletal anatomy of the cheetah forelimb and compare it to the racing greyhound, an animal of similar mass, but which can only attain a top speed of 17 m s(-1). Measurements were made of muscle mass, fascicle length and moment arms, enabling calculations of muscle volume, physiological cross-sectional area (PCSA), and estimates of joint torques and rotational velocities. Bone lengths, masses and mid-shaft cross-sectional areas were also measured. Several species differences were observed and have been discussed, such as the long fibred serratus ventralis muscle in the cheetah, which we theorise may translate the scapula along the rib cage (as has been observed in domestic cats), thereby increasing the cheetah's effective limb length. The cheetah's proximal limb contained many large PCSA muscles with long moment arms, suggesting that this limb is resisting large ground reaction force joint torques and therefore is not functioning as a simple strut. Its structure may also reflect a need for control and stabilisation during the high-speed manoeuvring in hunting. The large digital flexors and extensors observed in the cheetah forelimb may be used to dig the digits into the ground, aiding with traction when galloping and manoeuvring. PMID:21332715

Hudson, Penny E; Corr, Sandra A; Payne-Davis, Rachel C; Clancy, Sinead N; Lane, Emily; Wilson, Alan M

2011-04-01

42

Gait analysis in a cat with scapular luxation and contralateral forelimb amputation  

PubMed Central

This report describes the use of a pressure-sensitive walkway to evaluate an uncommon case of a cat with dorsal luxation of the left scapula and an amputated right forelimb. The findings suggest that limb amputation induced load redistribution mostly to the contralateral forelimb despite the scapular luxation.

Kano, Washington Takashi; Rahal, Sheila C; Mesquita, Luciane dos Reis; Agostinho, Felipe Stefan; de Faria, Luis Guilherme

2013-01-01

43

Novel model for end-neuroma formation in the amputated rabbit forelimb  

Microsoft Academic Search

BACKGROUND: The forelimb amputee poses many reconstructive challenges in the clinical setting, and there is a paucity of established surgical models for study. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model. METHODS: Upon approval from the Institutional Animal Care and Use Committee, 5 New Zealand White rabbits underwent left

Peter S Kim; Jason Ko; Kristina K O'Shaughnessy; Todd A Kuiken; Gregory A Dumanian

2010-01-01

44

A three-dimensional analysis of morphological evolution and locomotor performance of the carnivoran forelimb.  

PubMed

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

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

2014-01-01

45

Enriched Rehabilitative Training Promotes Improved Forelimb Motor Function and Enhanced Dendritic Growth after Focal Ischemic Injury  

Microsoft Academic Search

Chronic impairment of forelimb and digit movement is a com- mon problem after stroke that is resistant to therapy. Previous studies have demonstrated that enrichment improves behav- ioral outcome after focal ischemia; however, postischemic en- richment alone is not capable of enhancing fine digit and forelimb function. Therefore, we combined environmental en- richment with daily skilled-reach training to assess the

Jeff Biernaskie; Dale Corbett

2001-01-01

46

Fore-aft ground force adaptations to induced forelimb lameness in walking and trotting dogs.  

PubMed

Animals alter their locomotor mechanics to adapt to a loss of limb function. To better understand their compensatory mechanisms, this study evaluated the changes in the fore-aft ground forces to forelimb lameness and tested the hypothesis that dogs unload the affected limb by producing a nose-up pitching moment via the exertion of a net-propulsive force when the lame limb is on the ground. Seven healthy Beagles walked and trotted at steady speed on an instrumented treadmill while horizontal force data were collected before and after a moderate lameness was induced. Peak, mean and summed braking and propulsive forces as well as the duration each force was exerted and the time to reach maximum force were evaluated for both the sound and the lame condition. Compared with the sound condition, a net-propulsive force was produced by the lame diagonal limbs due to a reduced braking force in the affected forelimb and an increased propulsive force in the contralateral hindlimb when the dogs walked and trotted. To regain pitch stability and ensure steady speed for a given locomotor cycle, the dogs produced a net-braking force when the sound diagonal limbs were on the ground by exerting greater braking forces in both limbs during walking and additionally reducing the propulsive force in the hindlimb during trotting. Consistent with the proposed mechanism, dogs maximize their double support phases when walking. Likely associated with the fore-aft force adaptations to lameness are changes in muscle recruitment that potentially result in short- and long-term effects on the limb and trunk muscles. PMID:23300614

Abdelhadi, Jalal; Wefstaedt, Patrick; Nolte, Ingo; Schilling, Nadja

2012-01-01

47

Electroacupuncture Reduces Hyperalgesia after Injections of Acidic Saline in Rats  

PubMed Central

Background. Injections of acidic saline into the gastrocnemius muscle in rats produce a bilateral long-lasting hyperalgesia similar to fibromyalgia in humans. No previous study investigated the effect of electroacupuncture (EA) on this acidic saline model. This study aimed to identify the effects of EA in the hyperalgesia produced by repeated intramuscular injections of acidic saline. Methods. Rats were divided into four groups (n = 6, each group): control, acupuncture, EA 15?Hz, and 100?Hz. Left gastrocnemius muscle was injected with 100??L of pH 4.0 sterile saline twice five days apart. EA, acupuncture, or control therapy was daily administered (20?min) for 5 consecutive days under anesthesia. Needles were placed in the St36 and Sp6 acupoints. The assessment of secondary mechanical hyperalgesia, thermal hyperalgesia, and motor performance was performed before injections and before and after the treatment performed on each day. The paw withdrawal threshold was tested using the nonparametric Kruskal-Wallis test and differences within the group Wilcoxon Matched Pairs. The latency and motor performance were tested for ANOVA parametric test for independent measures, and for differences in the group, we used t-test for paired samples. Post hoc Tukey test was used for multiple corrections. P values less than 0.05 were considered statistically significant. Results. Indicate that there was a significant reduction of mechanical withdrawal threshold and paw withdrawal latency 24 hours following the second injection. Moreover, mechanical and thermal hyperalgesia were significantly reversed by EA 15, 100?Hz, and acupuncture. Conclusions. The results suggest that EA high and low frequency as well as acupuncture are effective in reducing hyperalgesia in chronic muscle pain model.

Maciel, Leonardo Yung dos Santos; da Cruz, Kamilla Mayara Lucas; de Araujo, Ariane Martins; Silva, Zak Moreira de Andrade; Badaue-Passos, Daniel; Santana-Filho, Valter Joviniano; DeSantana, Josimari Melo

2014-01-01

48

Morphological integration in the forelimb of musteloid carnivorans.  

PubMed

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

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

2014-07-01

49

Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys.  

PubMed

Primary motor cortex (M1) movement representations reflect acquired motor skills. Representations of muscles and joints used in a skilled task expand. However, it is unknown whether motor restriction in healthy individuals results in complementary reductions in M1 representations. With the use of intracortical microstimulation techniques in squirrel monkeys, detailed maps of movement representations in M1 were derived before and up to 35 wk after restriction of the preferred distal forelimb (DFL) by use of a soft cast. Although total DFL area and movement threshold remained constant, casting resulted in a redistribution of digit and wrist/forearm representations. Digit representations progressively decreased, whereas wrist/forearm representations progressively increased in areal extent. In three of four monkeys, hand preference returned to normal by the end of the postcast recovery period, and postrecovery maps demonstrated reversal of restriction-induced changes. However, in one monkey, a chronic motor impairment occurred in the casted limb. Rehabilitation via a forced-use paradigm resulted in recovery in use and skill of the impaired limb, as well as restoration of normal motor maps. These results demonstrate that plasticity in motor representations can be induced by training or restricting movements of the limb. Physiological changes induced by restriction appear to be reversible, even in the case of adverse motor outcomes. The respective contributions of both disuse and lost motor skills are discussed. These results have relevance for clinical conditions requiring forelimb casting as well as interpreting the differential effects of injury and disuse that are necessarily intertwined after cortical injury, as occurs in stroke. PMID:23236004

Milliken, Garrett W; Plautz, Erik J; Nudo, Randolph J

2013-03-01

50

Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats  

PubMed Central

Cocaine generates drug-seeking behavior by creating long-lasting changes in the reward pathway. The role of the growth factor, brain-derived neurotrophic factor (BDNF) in facilitating these changes was investigated in the present report with a genetic rat model. Using conditioned place preference, the current study investigated the hypothesis that a partial knockout of the BDNF gene in rats (BDNF+/?) would attenuate the rewarding effects of cocaine. Wildtype rats exposed to cocaine exhibited normal cocaine-seeking responses one day after conditioning and cocaine-seeking behavior was reinstated with drug priming following drug abstinence. In contrast, BDNF+/? rats did not show cocaine-seeking behavior one day after conditioning, nor did they respond to drug priming. A median split of rats based on BDNF levels in sera collected prior to behavioral procedures revealed that wildtype rats with high BDNF levels showed stronger conditioned place preference and reinstatement to cocaine. Together, the results support the hypothesis that a partial knockout of the BDNF gene attenuates the rewarding properties of cocaine. Additionally, individual differences in BDNF levels may predict future cocaine-seeking behavior. An underlying mechanism of these effects may be a reduction of the amount of synaptic changes made in the reward pathway.

St Laurent, Robyn; Helm, Samuel R.; Glenn, Melissa J.

2013-01-01

51

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

PubMed

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

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

2013-12-01

52

Frequency Analysis of Vestibular Influence on Extensor Motoneurons. I. Response to Tilt in Forelimb Extensors.  

National Technical Information Service (NTIS)

The experiments were conducted with the aim of obtaining a quantitative description of the dynamic relationships between motor unit activity in forelimb extensor muscles and vestibular inputs. A frequency analysis of the EMG response to sinusoidal angular...

A. Berthoz J. H. Anderson

1971-01-01

53

The pectoral girdle and forelimb of the basal theropod Herrerasaurus ischigualastensis  

Microsoft Academic Search

New specimens of Herrerasaurus ischigualastensis shed light on the structure and function of the pectoral girdle and forelimb in early theropod dinosaurs. As in tetanurian theropods, the scapulocoracoid has a broadly expanded acromion and strap-shaped scapular blade. The forelimb is less than one-half the length of the hind-limb and is specialized for prey capture and manipulation. The short proximal segments

Paul C. Sereno

1994-01-01

54

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

PubMed

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

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

2008-12-19

55

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling  

PubMed Central

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

56

Influence of Reduced Food Intake on Polyunsaturated Fatty Acid Metabolism in Zinc-Deficient Rats1  

Microsoft Academic Search

The influence of reduced food intake on metabolism of liver phos- pholipids (PL) in zinc-deficient (ZD) rats was measured. Wealing male Long-Evans rats were fed ad libitum zinc-deficient (2 jig Zn\\/g diet) and zinc-adequate (20 \\/ig Zn\\/g diet) diets for 21 days. A pair-fed (PF) group was included. ZD and PF rats displayed significantly increased levels of linoleic (18:2co6) and

TIM R. KRAMER; SUSAN B. JOHNSON; ANDRALPH T. HOLMAN

57

Subcutaneous daidzein administration enhances recovery of skilled ladder rung walking performance following stroke in rats.  

PubMed

Stroke is a devastating event which can result in permanent disability. Due to the lack of treatments available for use after stroke, compounds which work to limit cell loss, reduce behavioral deficits, and enhance recovery of function are needed. The isoflavone daidzein has been demonstrated to be neuroprotective when fed to rats beginning prior to stroke. Herein, we tested whether subcutaneous delivery of daidzein beginning at the time of stroke reduced injury and/or enhanced functional recovery over 14 days after stroke. Baseline performance on the skilled ladder rung walking task was recorded immediately before stroke (Day 0). Rats then underwent a unilateral permanent middle cerebral artery occlusion and received a subcutaneous minipump containing either daidzein dissolved in vehicle or vehicle alone. Performance on the skilled ladder rung walking task was recorded again on Day +3, Day +7, and Day +14 post-stroke. Rats were then euthanized and brains were collected for lesion volume analysis. The numbers of slight and deep forelimb slips on the task were recorded for 3 trials for each rat per day. Rats treated with daidzein exhibited fewer deep slips over the course of the experiment than rats which received only vehicle (p<0.05). No difference was detected in total forelimb slips or slight slips (p>0.05). Lesion volume was not different between groups (p>0.05). No differences were found in weight between groups during the study (p>0.05). PMID:23994543

Stout, Jessica M; Knapp, Austen N; Banz, William J; Wallace, Douglas G; Cheatwood, Joseph L

2013-11-01

58

Dynamic motor compensations with permanent, focal loss of forelimb force after cervical spinal cord injury.  

PubMed

Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. Overuse of both contralateral legs and ipsilateral hind leg was evidenced since 5 days postlesion. Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2-C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments. PMID:23249275

López-Dolado, Elisa; Lucas-Osma, Ana M; Collazos-Castro, Jorge E

2013-02-01

59

Memory Retrieval before or after Extinction Reduces Recovery of Fear in Adolescent Rats  

ERIC Educational Resources Information Center

Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a…

Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

2013-01-01

60

Reduced Interferon g Secretion by Natural Killer Cells from Rats Susceptible to Postviral Chronic Airway Dysfunction  

Microsoft Academic Search

After parainfluenza type 1 (Sendai) virus infection as wean- lings, Brown Norway (BN), unlike Fischer 344 (F344), rats de- velop an asthma-like phenotype. Reduced postinfection inter- feron (IFN)- g levels in bronchoalveolar lavage fluid from BN weanlings and the prevention of chronic airway sequelae in BN rats by IFN- g treatment led to the hypothesis that cells from BN weanlings

Lance D. Mikus; Louis A. Rosenthal; Ronald L. Sorkness; Robert F. Lemanske

61

Sensory stimulation (massage) reduces blood pressure in unanaesthetized rats  

Microsoft Academic Search

The objective of this study was to investigate how sensory stimulation by massage-like stroking influences blood pressure and heart rate in conscious rats. Also, the influence of different locations and durations of the stimulation were assessed. For this purpose, the ventral side of the abdomen or the dorsal side of the back was manually stroked at a speed of approximately

Iréne Lund; Thomas Lundeberg; Mieko Kurosawa; Kerstin Uvnäs-Moberg

1999-01-01

62

Immediate Postsession Feeding Reduces Operant Responding in Rats  

ERIC Educational Resources Information Center

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…

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

2012-01-01

63

Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat.  

PubMed

The purpose of this study was to determine the importance of the rubrospinal pathway and the ascending components of the dorsal column for overground locomotion in adult, unrestrained rats. The dorsal column (excluding the corticospinal tract), the rubrospinal tract or both were damaged unilaterally in rats at the level of the upper cervical spinal cord. Behavioural analysis consisted of skilled locomotion (an evaluation of footslips during ladder walking), a paw usage task and the assessment of ground reaction forces during unrestrained locomotion. All lesioned animals used the forepaw ipsilateral to the lesions less while rearing. Animals with dorsal column injuries used the forelimb contralateral to the spinal injury significantly more while rearing compared with uninjured animals. All lesioned animals produced more footfalls while crossing the ladder compared with uninjured animals. All injuries, regardless of the pathway affected, resulted in significant alterations in body weight support and reduced braking forces from the forelimb ipsilateral to the injury during overground locomotion. Animals typically bore less weight on the hindlimb ipsilateral to the lesion compared with the hindlimb contralateral to the spinal injury. Taken together with previously published work, our data indicate that the rubrospinal and dorsal column pathways are important for forelimb support while rearing and for skilled locomotion. Additionally, the ascending dorsal column pathways and the rubrospinal tract play a role during flat surface overground locomotion and combined damage to these pathways does not alter the acquired gait. PMID:12887423

Webb, Aubrey A; Muir, Gillian D

2003-07-01

64

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

PubMed Central

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.

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

2009-01-01

65

Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney  

Microsoft Academic Search

Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney.BackgroundMyofibroblasts have been shown to play a pivotal role in the synthesis of extracellular matrix components in several animal models of renal fibrosis. The purpose of the present study was to investigate whether mycophenolate mofetil (MMF) reduces interstitial myofibroblast infiltration and collagen III deposition in 5\\/6 nephrectomized rats.MethodsForty-five

Chérif Badid; Madeleine Vincent; Brigitte Mcgregor; Martine Melin; Aoumeur Hadj-Aissa; Cécile Veysseyre; Daniel J. Hartmann; Alexis Desmouliere; Maurice Laville

2000-01-01

66

Effects of magnesium citrate and phytin on reducing urinary calcium excretion in rats  

Microsoft Academic Search

The aim of this study was to determine and compare the effects of both magnesium citrate and phytin on reducing urinary calcium excretion under high-calcium-diet conditions during single and combined treatments. An animal experiment was carried out over a period of 4 weeks in 35 male rats. Urinary calcium excretion was reduced significantly by magnesium citrate and\\/or phytin in rats

N. Wu; W. F. Thon; H. Krah; R. Schlick; U. Jonas

1994-01-01

67

Magnesium and riboflavin combination therapy following cortical contusion injury in the rat.  

PubMed

Previous research has shown that magnesium chloride (MgCl(2)) and riboflavin (B(2)) both significantly improve functional recovery when administered shortly after frontal cortical contusion injury (CCI). The purpose of the present study was to examine the ability of combination treatments of MgCl(2) and B(2) to improve functional outcome following unilateral CCI. One hour post-injury, rats were administered MgCl(2) (1.0 mmol/kg), B(2) (7.5mg/kg), MgCl(2)+B(2) (1 mmol/kg+7.5mg/kg), 1/2 MgCl(2)+1/2 B(2) (0.5 mmol/kg and 3.75 mg/kg), or saline. Two days following CCI rats were tested on a battery of sensorimotor (vibrissae-->forelimb placing and tactile removal test) and motor (staircase test). A regimen of MgCl(2)+B(2) significantly reduced the initial impairment and facilitated the rate of recovery on the tactile removal test and facilitated the rate of recovery on the forelimb placing test. The half-dose combination did not significantly improve functional recovery on the tactile removal test compared to the individual treatments; however, it did improve performance on the forelimb placing test compared to saline treatment. Administration of MgCl(2) improved performance on the placing and tactile removal tests on 2 post-operative days, as did treatment with B(2) on the tactile removal test. The results indicate that the full combination of MgCl(2)+B(2) significantly improved functional recovery to a greater extent than the individual treatments or the low dose combination group on forelimb placing but not on tactile removal. These findings suggest that administration of MgCl(2)+B(2) may provide better therapeutic action than individual treatments. PMID:16716831

Barbre, Adrianne B; Hoane, Michael R

2006-05-31

68

Regulation of carbonyl-reducing enzymes in rat liver by chemoprotectors.  

PubMed

Feeding rats on diets containing the synthetic antioxidants ethoxyquin, butylated hydroxyanisole, and oltipraz results in 15-, 9-, and 6-fold increases, respectively, in the hepatic levels of aflatoxin B1-dialdehyde reductase (AFAR) protein. By contrast, treatment of rats with either of the inducing agents phenobarbital or 3-methylcholanthrene results in an approximate increase of only 1.4-fold in the amount of AFAR in rat liver. Northern blotting has shown that these increases in levels of hepatic AFAR protein are accompanied by corresponding increases in AFAR mRNA. Immunodepletion of AFAR from rat liver extracts has revealed that AFAR makes a considerable contribution to carbonyl metabolism in livers from animals treated with synthetic antioxidants and that it is the major reductase that can utilize aflatoxin B1-dialdehyde as a substrate. The immunodepletion experiments also revealed the presence of at least one other inducible carbonyl-reducing enzyme that, like AFAR, can metabolize 9,10-phenanthraquinone. Carbonyl-reducing activity from rat liver has been resolved into six enzyme-containing peaks by anion-exchange chromatography on Q-Sepharose. This method has been used to show that, in addition to AFAR, two other rat liver carbonyl-reducing enzymes are induced by ethoxyquin, and that these are distinct from NAD(P)H: quinone oxidoreductase. Collectively, these data show that synthetic antioxidants can influence substantially the capacity of rat liver to metabolize reactive carbonyl-containing compounds. PMID:8665510

Ellis, E M; Judah, D J; Neal, G E; O'Connor, T; Hayes, J D

1996-06-15

69

Immediate Postsession Feeding Reduces Operant Responding in Rats  

PubMed Central

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.

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

2012-01-01

70

Reduced hedonic behavior and altered cardiovascular function induced by mild sodium depletion in rats.  

PubMed

Interactions among sodium homeostasis, fatigue, mood, and cardiovascular regulation have been described previously. The present study investigates the effects of sodium deficiency on an index of mood (hypohedonia; Experiment 1), cardiovascular function (Experiment 2), and plasma electrolytes (Experiment 3) in rats. Following 48 hr of sodium depletion with a diuretic (furosemide) and a sodium deficient diet, rats displayed hypohedonia evidenced by reduced responding for rewarding electrical brain stimulation into the hypothalamus. Also, sodium depletion produced increased heart rate and reduced heart rate variability. Plasma sodium levels were lower in sodium-depleted rats versus control rats, whereas potassium levels were unchanged. Thus, mild sodium depletion produces hypohedonia and cardiovascular alterations, which has implications for understanding behavioral and cardiovascular consequences of sodium deficiency. PMID:17014263

Grippo, Angela J; Moffitt, Julia A; Beltz, Terry G; Johnson, Alan Kim

2006-10-01

71

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats  

PubMed Central

Background Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. Methods In this study, we used adult Wistar rats to examine gender differences in the effects of NR2B NMDA antagonism at the level of the anterior cingulate cortex in phasic pain, and in the first and second phases of a formalin test. Rats underwent stereotactic surgery for cannula implantation in the anterior cingulate cortex. After recovery, paw withdrawal latency to a noxious thermal stimulus was assessed. Rats were also subjected to a formalin pain test whereby 60 ?L of 5% formalin was injected into the right hind paw. Results Female and male rats that received Ro 25-6981, an NR2B antagonist, before formalin injection showed significantly reduced pain responses to the formalin test compared with saline-injected control rats (P < 0.05). No gender differences in phasic pain responses were found in rats treated with Ro 25-6981. Conclusion These results suggest that cortical antagonism of the NR2B subunit reduces inflammatory pain levels in both genders of rat.

Quintero, Gabriel C; Herrera, Jairo; Bethancourt, Jose

2011-01-01

72

Pyramid environment reduces the wound healing suppressant properties of dexamethasone in albino rats.  

PubMed

With a view to investigate the contribution and role of environment within a wooden pyramid model on the wound healing suppressant effect of dexamethasone in rats, wound breaking strength, dry weight, hydroxyproline content and histology of granulation tissue of the dead space wound were studied in rats. The results indicate that the environment within the wooden pyramid not only promotes significant wound healing but also reduces the wound healing suppressant effect of dexamethasone. Histological studies also confirmed the results. PMID:15266915

Nayak, Surekha; Rao, S Gurumadhva; Murthy, K Dilip; Somayaji, S N; Bairy, K L

2003-06-01

73

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

Microsoft Academic Search

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

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

2005-01-01

74

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

Microsoft Academic Search

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

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

2003-01-01

75

Sucrose ingestion elicits reduced Fos expression in the nucleus accumbens of anhedonic rats.  

PubMed

Chronic mild stress (CMS), an animal model of depression associated with anhedonia, was used to examine nucleus accumbens (NAc) activation associated with a rewarding stimulus. Following 4 weeks of CMS in rats, NAc Fos-immunoreactivity was measured after ingestion of a fixed volume of sucrose. Fewer Fos-positive neurons were observed in the NAc in CMS versus control rats. These findings have implications for the mechanisms underlying reduced responding to pleasurable stimuli associated with depression. PMID:15306261

Grippo, Angela J; Na, Elisa S; Johnson, Ralph F; Beltz, Terry G; Johnson, Alan Kim

2004-09-01

76

Supplemental oxygen reduces right ventricular hypertrophy in monocrotaline-injected rats.  

PubMed

We evaluated the possible contributory role of hypoxia in the development of monocrotaline-induced pulmonary hypertension. Male Sprague-Dawley rats were injected subcutaneously with monocrotaline (60 mg/kg) or saline in controls and were kept in oxygen-enriched (inspired O2 fraction of 0.35) or compressed air chambers. After 21 days, rats were anesthetized while spontaneously breathing room air, hemodynamic parameters and arterial blood gases were measured, and animals were killed. Right ventricular peak systolic pressures (RVPP), right ventricular-to-left ventricular plus septal weight ratios (RV/LV + S), hematocrits, lung dry weight-to-body weight ratios, and medial thickness of pulmonary arteries were significantly reduced in monocrotaline-injected rats exposed to mild hyperoxia compared with air. The air-exposed monocrotaline-injected rats had significantly more arterial hypoxemia than the other groups, and mild hyperoxia had no effect on any of the measured variables in saline-injected rats. To determine whether the effects of mild hyperoxia occurred early or late after monocrotaline injection, we moved separate groups of rats from air to mild hyperoxia and vice versa 10 days after monocrotaline injection. After 21 days, significant reductions in RVPP and RV/LV + S occurred only in rats exposed to mild hyperoxia during the latter 11 days after injection. Our findings suggest that hypoxia contributes to the development of pulmonary hypertension relatively late after monocrotaline injection in rats but that it does not influence the early injury. PMID:2525121

Hill, N S; Jederlinic, P; Gagnon, J

1989-04-01

77

Chronic lithium feeding reduces upregulated brain arachidonic acid metabolism in HIV-1 transgenic rat  

PubMed Central

Background HIV-1 transgenic (Tg) rats, a model for human HIV-1 associated neurocognitive disorder (HAND), show upregulated markers of brain arachidonic acid (AA) metabolism with neuroinflammation after 7 months of age. Since lithium decreases AA metabolism in a rat lipopolysaccharide model of neuroinflammation, and may be useful in HAND, we hypothesized that lithium would dampen upregulated brain AA metabolism in HIV-1 Tg rats. Methods Regional brain AA incorporation coefficients k* and rates Jin, markers of AA signaling and metabolism, were measured in 81 brain regions using quantitative autoradiography, after intravenous [1-14C] AA infusion in unanesthetized 10-month-old HIV-1 Tg and age-matched wildtype rats that had been fed a control or LiCl diet for 6 weeks. Results k* and Jin for AA were significantly higher in HIV-1 Tg than wildtype rats fed the control diet. Lithium feeding reduced plasma unesterified AA concentration in both groups and Jin in wildtype rats, and blocked increments in k* (19 of 54 regions) and Jin (77 of 81 regions) in HIV-1 Tg rats. Conclusion These in vivo neuroimaging data indicate that lithium treatment dampened upregulated brain AA metabolism in HIV-1 Tg rats. Lithium may improve cognitive dysfunction and be neuroprotective in HIV-1 patients with HAND through a comparable effect.

Ramadan, Epolia; Basselin, Mireille; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

2012-01-01

78

Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats.  

PubMed

The antioxidant properties of amla extracts and their effects on the oxidative stress in streptozotocin-induced diabetes were examined in rats. Amla in the form of either the commercial enzymatic extract SunAmla (Taiyo Kagaku Co. Ltd., Yokkaichi, Japan) (20 or 40 mg/kg of body weight/day) or a polyphenol-rich fraction of ethyl acetate extract (10 or 20 mg/kg of body weight/day) was given orally for 20 days to the streptozotocin-induced diabetic rats. Amla extracts showed strong free radical scavenging activity. Amla also showed strong inhibition of the production of advanced glycosylated end products. The oral administration of amla extracts to the diabetic rats slightly improved body weight gain and also significantly alleviated various oxidative stress indices of the serum of the diabetic rats. The elevated serum levels of 5-hydroxymethylfurfural, which is a glycosylated protein that is an indicator of oxidative stress, were significantly reduced dose-dependently in the diabetic rats fed amla. Similarly, the serum level of creatinine, yet another oxidative stress parameter, was also reduced. Furthermore, thiobarbituric acid-reactive substances levels were significantly reduced with amla, indicating a reduction in lipid peroxidation. In addition, the decreased albumin levels in the diabetic rats were significantly improved with amla. Amla also significantly improved the serum adiponectin levels. These results form the scientific basis supporting the efficacy of amla for relieving the oxidative stress and improving glucose metabolism in diabetes. PMID:16176148

Rao, T P; Sakaguchi, N; Juneja, L R; Wada, E; Yokozawa, T

2005-01-01

79

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

PubMed

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 the carcinogen-initiated group were given a diet with 5% PEG 8000 in an AIN-93 based, high fat diet. The other nine, and the control group received the diet without the addition of PEG. Nine weeks later, the rats receiving the diet containing PEG had a 43% reduction in ACF (P<0.001) compared with the carcinogen-initiated rats on the control diet, a result confirming earlier observations that PEG inhibits colon carcinogenesis. The animals receiving the diet containing PEG also had a 10-fold reduction in fecal granulocyte marker protein (GMP) (P<0.001) compared with both the carcinogen-treated and the control animals. PEG reduced inflammation below the levels of carcinogen-treated and of untreated animals. Fecal water from the rats receiving PEG did not reduce transepithelial resistance of, or manitol flux through, human Caco-cells grown as monolayers in vitro. PEG may reduce colon carcinogenesis through a mechanism involving colonic inflammation. PMID:15896454

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

2005-06-01

80

Energy Restriction Reduces Bone Density and Biomechanical Properties in Aged Female Rats1,2  

PubMed Central

Bone mineral density (BMD) is highly correlated with body weight, and weight loss is associated with reduced BMD. Whether such losses of BMD increase skeletal fragility is unclear. We examined the effect of 9 wk of energy restriction (ER) on bone density, mineral and matrix protein composition and biomechanical properties in mature (20 wk old, n = 12) and aged (48 wk old, n = 16) female rats. Energy-restricted rats were fed 40% less energy than controls that consumed food ad libitum. Bone content of mineral (ash and calcium content) and matrix proteins (hydroxyproline, pyridinium crosslinks and proteoglycans), serum hormones, site-specific bone density and biomechanical properties (peak load, peak torque, shear stiffness and bending stiffness) were measured at the conclusion of the study. In both age groups, ER reduced body weight by 15 ± 10% (P < 0.001) and dramatically decreased femoral bone density by 32–35% (P < 0.01) compared with controls. Energy restriction resulted in a small reduction in tibia and humerus density, as well as biomechanical properties in the aged but not mature rats (P < 0.05). Reduced serum levels of insulin and estradiol due to ER in aged rats (P < 0.05) may play a role in altering bone quality. These data show that although weight loss due to ER is detrimental to some bone parameters in mature rats, only aged rats show consistent reductions in bone density and biomechanical properties.

Talbott, Shawn M.; Cifuentes, Mariana; Dunn, Michael G.; Shapses, Sue A.

2014-01-01

81

Oxyntomodulin Reduces Hydromineral Transport Through Rat Small Intestine  

Microsoft Academic Search

Glicentin (GLIC) and oxyntomodulin (OXM) arereleased from the ileum and colon during digestion. Bothhormones reduce fluid and proton secretion in thestomach. The luminal concentration of sodium andchloride underlying the nutrient absorption, the effectof OXM on electrolyte transport through the smallintestine, was assessed in vivo using ligated loops andin vitro using Ussing chambers. In vivo , a zero transport state, estimated

F. Beauclair; B. Eto; D. Pansu; G. Rodier; T. Mochizuki; J. Martinez; D. Bataille; C. Jarrousse

1998-01-01

82

Red maca (Lepidium meyenii) reduced prostate size in rats  

Microsoft Academic Search

BACKGROUND: Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher

Gustavo F Gonzales; Sara Miranda; Jessica Nieto; Gilma Fernández; Sandra Yucra; Julio Rubio; Pedro Yi; Manuel Gasco

2005-01-01

83

Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats.  

PubMed

The action of gliclazide, a sulphonylurea with beneficial extrapancreatic effects in diabetes, may be enhanced by administering probiotics. The aim of this study was to investigate the influence of probiotics on gliclazide pharmacokinetics and the effect of both probiotics and gliclazide on blood glucose levels in healthy and diabetic rats. Male Wistar rats (2 to 3 months, weight 350 +/- 50 g) were randomly allocated to 4 groups (n =10), two of which were treated with alloxan i.v. 30 mg/kg to induce diabetes. One group of healthy and one group of diabetic rats were then gavaged with probiotics (75 mg/kg) for three days after which a gliclazide suspension (20 mg/kg) was administered by gavage to all groups. Blood samples were collected from the tail vein at various time points for 10 hours post-administration for the determination of blood glucose and gliclazide serum concentrations. It was found that probiotic treatment had no effect on blood glucose levels in healthy rats, but it reduced them (up to 2-fold; p < 0.01) in diabetic rats. Probiotic treatment reduced gliclazide bioavailability in healthy rats (3-fold) whereas it increased gliclazide bioavailability in diabetic rats (2-fold; p < 0.01). Gliclazide had no effect on blood glucose levels in either healthy or diabetic rats despite the changes in its bioavailability. In conclusion, the probiotic treatment of diabetic rats increases gliclazide bioavailability and lowers blood glucose levels by insulin-independent mechanisms, suggesting that the administration of probiotics may be beneficial as adjunct therapy in the treatment of diabetes. PMID:18777945

Al-Salami, Hani; Butt, Grant; Fawcett, J Paul; Tucker, Ian G; Golocorbin-Kon, Svetlana; Mikov, Momir

2008-01-01

84

Systemic propranolol acts centrally to reduce conditioned fear in rats without impairing extinction  

PubMed Central

Background Previous work has implicated noradrenergic beta-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The beta-receptor blocker propranolol has been used clinically to reduce anxiety. Using an auditory fear conditioning task in rats, we assessed the effects of propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar pressing. Methods One day after receiving auditory fear conditioning, rats were injected with saline, propranolol or peripheral blocker sotalol (both 10 mg/kg, ip). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed. Results Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, the peripheral blocker sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons. Conclusion Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

Rodriguez-Romaguera, Jose; Sotres-Bayon, Francisco; Mueller, Devin; Quirk, Gregory J.

2009-01-01

85

Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats  

PubMed Central

Cow’s milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague Dawley rats were given either whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene (DMBA) on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p<0.001) and accelerated vaginal opening, which marks puberty onset, by 2.5 days (p<0.001). However, rats exposed to milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; i.e., their tumor latency was longer (p<0.03) and incidence was lower (p<0.05) than in the controls. On PND 25 and 50, mammary glands of the milk exposed rats had significantly less terminal end buds (TEBs) than the tap water exposed controls (p<0.019). ER-? protein levels were elevated in the TEBs and lobules of milk rats, compared to rats given tap water (p<0.019), but no changes in cyclin D1 expression, cell proliferation or apoptosis were seen. IGF-1 mRNA levels were reduced on PND 50 in the mammary glands of rats exposed to milk at puberty. Our results suggest that drinking milk before puberty reduces later risk of developing mammary cancer in rats. This might be mediated by a reduction in the number of TEBs and lower expression of IGF-1 mRNA in the mammary glands of milk-exposed animals.

Nielsen, Tina S.; Khan, Galam; Davis, Jennifer; Michels, Karin B.; Hilakivi-Clarke, Leena

2010-01-01

86

Comparative anatomy, evolution, and homologies of tetrapod hindlimb muscles, comparison with forelimb muscles, and deconstruction of the forelimb-hindlimb serial homology hypothesis.  

PubMed

For more than two centuries, the idea that the forelimb and hindlimb are serially homologous structures has been accepted without serious question. This study presents the first detailed analysis of the evolution and homologies of all hindlimb muscles in representatives of each major tetrapod group and proposes a unifying nomenclature for these muscles. These data are compared with information obtained previously about the forelimb muscles of tetrapods and the muscles of other gnathostomes in order to address one of the most central and enigmatic questions in evolutionary and comparative anatomy: why are the pelvic and pectoral appendages of gnathostomes generally so similar to each other? An integrative analysis of the new myological data, combined with a review of recent paleontological, developmental, and genetic works and of older studies, does not support serial homology between the structures of these appendages. For instance, many of the strikingly similar forelimb and hindlimb muscles found in each major extant tetrapod taxon were acquired at different geological times and/or have different embryonic origins. These similar muscles are not serial homologues, but the result of evolutionary parallelism/convergence due to a complex interplay of ontogenetic, functional, topological, and phylogenetic constraints/factors. PMID:24729440

Diogo, Rui; Molnar, Julia

2014-06-01

87

Inhibition of Cyclooxygenase-2 Reduces Hypothalamic Excitation in Rats with Adriamycin-Induced Heart Failure  

PubMed Central

Background The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure. Methodology/Principal Finding Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg). On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB) or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW) and lung to body weight (LW/BW) ratios, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak systolic pressure (LVPSP) and maximum rate of change in left ventricular pressure (LV±dp/dtmax) were improved in HF+CLB rats. Angiotensin II (ANG II), norepinephrine (NE), COX-2 and glutamate (Glu) in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH) positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. Conclusions These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

Liu, Wei; Zang, Wei-Jin; Bao, Cui-Yu; Qin, Da-Nian

2012-01-01

88

Hypomethylation of neuregulin in rats selectively bred for reduced sensorimotor gating.  

PubMed

Low prepulse inhibition (PPI) of startle is associated with reduced sensorimotor gating found in schizophrenia. In rats with breeding-induced low PPI neuregulin (NRG1) methylation was significantly decreased in brain regions associated with this phenotype and with schizophrenia, i.e., the medial prefrontal cortex, the nucleus accumbens, and the ventral hippocampus, while methylation in the amygdala and dorsal hippocampus was less affected. The dopamine D2 receptor (DRD2) promoter region showed negligible changes between groups. Rats with low PPI may be used to understand the reduced epigenetic regulation found in schizophrenia, and eventually lead to the development of novel therapies. PMID:23899995

Rhein, Mathias; Muschler, Marcel-René; Krauss, Joachim K; Bleich, Stefan; Frieling, Helge; Schwabe, Kerstin

2013-10-01

89

Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats  

PubMed Central

Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10–15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

Reno, Candace M.; Tanoli, Tariq; Bree, Adam; Daphna-Iken, Dorit; Cui, Chen; Maloney, Susan E.; Wozniak, David F.

2013-01-01

90

Pomegranate seed oil reduces intestinal damage in a rat model of necrotizing enterocolitis  

PubMed Central

Pomegranate seed oil (PSO), which is the major source of conjugated linolenic acids such as punicic acid (PuA), exhibits strong anti-inflammatory properties. Necrotizing enterocolitis (NEC) is a devastating disease associated with severe and excessive intestinal inflammation. The aim of this study was to evaluate the effects of orally administered PSO on the development of NEC, intestinal epithelial proliferation, and cytokine regulation in a rat model of NEC. Premature rats were divided into three groups: dam fed (DF), formula-fed rats (FF), or rats fed with formula supplemented with 1.5% of PSO (FF + PSO). All groups were exposed to asphyxia/cold stress to induce NEC. Intestinal injury, epithelial cell proliferation, cytokine production, and trefoil factor 3 (Tff3) production were evaluated in the terminal ileum. Oral administration of PSO (FF+PSO) decreased the incidence of NEC from 61 to 26%. Feeding formula with PSO improved enterocyte proliferation in the site of injury. Increased levels of proinflammatory IL-6, IL-8, IL-12, IL-23, and TNF-? in the ileum of FF rats were normalized in PSO-treated animals. Tff3 production in the FF rats was reduced compared with DF but not further affected by the PSO. In conclusion, administration of PSO protects against NEC in the neonatal rat model. This protective effect is associated with an improvement of intestinal epithelial homeostasis and a strong anti-inflammatory effect of PSO on the developing intestinal mucosa.

Coursodon-Boyiddle, Christine F.; Snarrenberg, Chelsea L.; Adkins-Rieck, Camille K.; Bassaganya-Riera, Josep; Hontecillas, Raquel; Lawrence, Peter; Brenna, J. Thomas; Jouni, Zeina E.

2012-01-01

91

Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats  

PubMed Central

In exercising skeletal muscle, vasoconstrictor responses to ?-adrenoceptor activation are attenuated in part by nitric oxide (NO) produced by the neuronal isoform of NO synthase (nNOS), which is expressed constitutively in skeletal muscle cells. In skeletal muscle of pregnant animals, nNOS mRNA is upregulated, suggesting that muscle nNOS expression is modulated by the steroid hormone oestrogen. Whether oestrogen-induced changes in nNOS expression have measurable effects on vasoregulation in skeletal muscle is unknown. In this study, we hypothesized that oestrogen deficiency would reduce muscle nNOS expression, resulting in impaired modulation of sympathetic vasoconstriction in exercising skeletal muscle. Compared to gonadally intact rats, we found that ovariectomized (OVX) rats were characterized by greater sympathetic vasoconstriction in contracting hindlimb and reduced nNOS, but not eNOS, in skeletal muscle. In addition, NOS inhibition resulted in a greater enhancement of sympathetic vasoconstriction in contracting hindlimbs of intact compared to OVX rats. These effects of oestrogen deficiency were prevented by chronic treatment of OVX rats with 17?-oestradiol, but not with chronic progesterone or acute oestradiol. Further analysis revealed that skeletal muscle nNOS correlated directly with plasma 17?-oestradiol and inversely with the magnitude of sympathetic vasoconstrictor responses in contracting hindlimbs. These data indicate that NO-dependent attenuation of sympathetic vasoconstriction in contracting skeletal muscle is impaired in oestrogen-deficient female rats, and suggest that this impairment may be mediated by reduced skeletal muscle nNOS expression.

Fadel, Paul J; Zhao, Weiying; Thomas, Gail D

2003-01-01

92

Muscular reconstruction and functional morphology of the forelimb of early Miocene sloths (Xenarthra, Folivora) of Patagonia.  

PubMed

Early Miocene sloths are represented by a diversity of forms ranging from 38 to 95 kg, being registered mainly from Santacrucian Age deposits in southern-most shores of Patagonia, Argentina. Their postcranial skeleton differs markedly in shape from those of their closest living relatives (arboreal forms of less than 10 kg), Bradypus and Choloepus. In order to gain insight on functional properties of the Santacrucian sloths forelimb, musculature was reconstructed and a comparative, qualitative morphofunctional analysis was performed, allowing proposing hypotheses about biological role of the limb in substrate preferences, and locomotor strategies. The anatomy of the forelimb of Santacrucian sloths resembles more closely extant anteaters such as Tamandua and Myrmecophaga, due to the robustness of the elements, development of features related to attachment of ligaments and muscles, and conservative, pentadactylous, and strong-clawed manus. The reconstructed forelimb musculature was very well developed and resembles that of extant Pilosa (especially anteaters), although retaining the basic muscular configuration of generalized mammals. This musculature allowed application of powerful forces, especially in adduction of the forelimb, flexion and extension of the antebrachium, and manual prehension. These functional properties are congruent with both climbing and digging activities, and provide support for proposed Santacrucian sloths as good climbing mammals, possibly arboreal or semiarboreal, being also capable diggers. Their climbing strategies were limited, thus these forms relied mainly on great muscular strength and curved claws of the manus to move cautiously on branches. PMID:23193102

Toledo, Néstor; Bargo, M Susana; Vizcaíno, Sergio F

2013-02-01

93

THE PECTORAL GIRDLE AND FORELIMB ANATOMY OF THE STEM-SAUROPODOMORPH SATURNALIA TUPINIQUIM (UPPER TRIASSIC, BRAZIL)  

Microsoft Academic Search

Description of the pectoral girdle (scapulocora- coid) and forelimb (humerus, radius and ulna) elements of two specimens of Saturnalia tupiniquim, a stem-sauro- podomorph from the Upper Triassic Santa Maria For- mation, southern Brazil, reveals a distinctive set of plesiomorphic, derived and unique traits, which shed light on the function and phylogenetic significance of these skel- etal elements within early dinosaurs.

MAX C. LANGER; MARCO A. G. FRANCA; STEFAN G ABRIEL

2007-01-01

94

Pituitary leptin gene expression is reduced by neonatal androgenization of female rats.  

PubMed

We have previously reported evidence of leptin gene expression (ob mRNA) in adult rat brain and pituitary gland. We have also shown that ob mRNA levels in female rat brain and pituitary are regulated in an age- and tissue-dependent fashion. In view of the known sexual dimorphism in adipose tissue leptin expression, we have extended our original work to include an assessment of ob mRNA levels in brain, pituitary and fat of developing male and female rats. In addition we determined the effects of neonatal androgenization of female rat pups with testosterone propionate. Leptin (ob) mRNA expression was evaluated using semi-quantitative RT-PCR analysis. Leptin mRNA levels were developmentally regulated in the pituitary and cortex of male rats, paralleling the changes previously observed in female rats. In the pituitary, leptin expression was significantly higher during the early postnatal period and dropped abruptly by postnatal day (PD) 22. In the cortex, leptin expression was lowest at PD 4 and rose significantly by PD 14. In addition gender differences, most notably in the pituitary, were also observed. In pituitary gland, ob mRNA was significantly higher in female rats than in males at PD 14 (+60%; p < 0.05) but there were no sex differences at PD 4 and PD 22. Testosterone treatment of neonatal female rats profoundly reduced ob mRNA at PD 14 (3.5-fold; p < 0.01) and PD 22 (3-fold; p = 0.05). In subcutaneous adipose tissue and hypothalamus we observed no sex difference in ob mRNA levels nor an effect of testosterone. We conclude that leptin gene expression in rat pituitary gland is sexually dimorphic and sensitive to neonatal manipulation of sex steroid levels. PMID:11824509

Morash, B A; Ur, E; Wilkinson, M

2001-01-01

95

Lactobacillus plantarum TN627 significantly reduces complications of alloxan-induced diabetes in rats.  

PubMed

This study aimed to assess the potential of the probiotic strain Lactobacillus plantarum TN627 for preventing alloxan-induced diabetes in rats. The oral administration of this probiotic was noted to significantly improve the immunological parameters, protect the pancreatic tissues, and reduce the pancreatic and plasmatic ?-amylase activities and level of plasma glucose in the treated as compared to the control group of rats. Furthermore, this probiotic treatment was observed to markedly reduce pancreatic and plasmatic lipase activities and serum triglyceride and LDL-cholesterol rates and to increase the level of HDL-Cholesterol. It also exerted efficient protective effects on the liver and kidney functions evidenced by significant decreases in serum aspartate transaminase, alanine transaminase, lactate dehydrogenase, and gamma-glutamyl transpeptidase activities, as well as creatinine and urea contents. Taken together, the findings indicate that L. plantarum TN627 exhibits attractive in vivo antidiabetic effects that may be helpful in preventing diabetic complications in adult rats. PMID:23999246

Bejar, Wacim; Hamden, Khaled; Ben Salah, Riadh; Chouayekh, Hichem

2013-12-01

96

Oxaliplatin induces hypomyelination and reduced neuregulin 1 expression in the rat sciatic nerve.  

PubMed

Oxaliplatin causes severe peripheral neuropathy. In this study, we examined hypomyelination in the peripheral nerve in oxaliplatin-induced neuropathy rat model. Gene expression of neuregulin 1 (NRG1), a myelination regulatory factor, is reduced in the dorsal root ganglion (DRG) in DNA microarray analysis. Oxaliplatin increased the g-ratio and reduced levels of myelin protein zero in sciatic nerve, suggesting the hypomyelination. Moreover, oxaliplatin reduced NRG1 mRNA levels in the DRG and decreased levels of cleaved NRG1 type III protein in the sciatic nerve. Our results indicate that oxaliplatin induces hypomyelination and reduced NRG1 expression. PMID:24530887

Tsutsumi, Kuniaki; Yamashita, Yuji; Ushio, Soichiro; Kawashiri, Takehiro; Kaname, Takanori; Fujita, Shunsuke; Oishi, Ryozo; Egashira, Nobuaki

2014-03-01

97

Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate  

Microsoft Academic Search

Epidemiological evidence links consumption of lycopene, the red carotenoid of tomato, to reduced prostate cancer risk. We investigated the effect of lycopene in normal prostate tissue to gain insight into the mechanisms, by which lycopene can contribute to primary prostate cancer prevention. We supplemented young rats with 200 ppm lycopene for up to 8 wk, measured the uptake into individual

Angelika Herzog; Ulrich Siler; Volker Spitzer; Nicole Seifert; Athanasios Denelavas; Petra Buchwald Hunziker; Willi Hunziker; Regina Goralczyk; Karin Wertz

2004-01-01

98

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.  

PubMed

Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10?l of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-? level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel. PMID:23085269

Barichello, Tatiana; Ceretta, Renan A; Generoso, Jaqueline S; Moreira, Ana Paula; Simões, Lutiana R; Comim, Clarissa M; Quevedo, João; Vilela, Márcia Carvalho; Zuardi, Antonio Waldo; Crippa, José A; Teixeira, Antônio Lucio

2012-12-15

99

Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis  

PubMed Central

Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1), obesity group (Group 2), obesity + MLT group (Group 3), and weight loss group (Group 4). Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5?cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P < 0.05). Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P < 0.05). There was no significant difference between groups in terms of mean Johnsen score (P = 0.727). Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

Atilgan, Dogan; Parlaktas, Bekir S.; Uluocak, Nihat; Erdemir, Fikret; Kilic, Sahin; Erkorkmaz, Unal; Ozyurt, Huseyin; Markoc, Fatma

2013-01-01

100

Partial lipectomy reduces dimethylhydrazine-induced carcinogenic initiation in the colon of rats.  

PubMed

This study investigated whether visceral adipose tissue directly modulates the development of preneoplastic lesions in the colon of carcinogen-treated rats. Wistar rats (n=64) were randomly assigned to 8 experimental groups in two experiments. In one experiment, 32 rats were exposed or not to either carcinogen treatment (dimethylhydrazine, DMH; 125 mg/kg) or high-fat diet (standard chow enriched with 14% lard) or both for 56 days. In a second experiment, 32 rats were exposed to a carcinogen or they underwent partial lipectomy or both for 30 days (partial lipectomy groups underwent ablation of mesenteric and parametrial fat pads, whereas sham groups did not; all rats were fed with standard chow). Colon was collected for histopathological analysis. After 56 experimental days a high-fat diet increased carcinogenic mutations in the colonic epithelia. Partial lipectomy reduced weight gain in carcinogen-exposed rats and decreased the de novo formation of mesenteric and parametrial fat pads. Partial lipectomy significantly inhibited the mutational process after 30 days: there were fewer colonic preneoplastic lesions and less proliferation, apoptosis, and inflammation. These data suggest that visceral adipose tissue promotes colon carcinogenesis and enhances the establishment and expansion of genetically mutated cells in colonic epithelia. PMID:24299902

Kannen, Vinicius; Moreira, Mauro César Silveira; Waaga-Gasser, Ana Maria; Modiano, Patricia; Elias Junior, Jorge; Fernandes, Cleverson R; Garcia, Sérgio B

2014-02-28

101

Comparision of uroprotective activity of reduced glutathione with Mesna in Ifosfamide induced hemorrhagic cystitis in rats  

PubMed Central

Background: Ifosfamide (IFO) is widely used DNA-alkylating agents in cancer chemotherapy for management of solid tumors and hematological malignancies. However, hemorrhagic cystitis limits the use of IFO. Objectives: To compare the efficiency of reduced glutathione with 2-Mesna in reducing Ifosfamide (IFO) induced hemorrhagic cystitis (HC) in wistar rats. Materials and Methods: Ifosfamide and 2-Mesna were dissolved in sterile water for injection and administered to wistar rats of albino strains. The rats were randomly assigned to one of the four groups of 6 rats each: Group I: Vehicle control; Group II: 120 mg/kg of IFO alone by intraperitoneal injection (i.p); Group III: 40 mg/kg Mesna i.p., at the same time and at 4 and 8 h after IFO administration; Group IV: 500 mg/kg of glutathione i.p., 30 min prior to IFO as above. The animals were observed for 5 days. On 6th day, rats were sacrificed by dissecting the intrajugular vein. The bladders were macroscopically and histopathologically evaluated. Results: Control animals had normal bladders with assigned scores of ‘0’ for the three parameters of edema, hemorrhage and histopathological changes. All the animals receiving IFO (group II) had evidence of HC as evidenced by alterations of edema and hemorrhages. These alterations were almost abolished (P < 0.001) by the glutathione (group III) or Mesna (group IV) in IFO-treated animals. Conclusion: Glutathione could be as useful as Mesna in the preventive management of IFO-induced HC.

Ali, Syed Amir; Danda, Sandeep Kumar; Basha, Syed Abdul Azeez; Rasheed, Asif; Ahmed, Osman; Ahmed, M. Muqtedar

2014-01-01

102

Propofol reduces inflammatory reaction and ischemic brain damage in cerebral ischemia in rats.  

PubMed

Our previous studies demonstrated that inflammatory reaction and neuronal apoptosis are the most important pathological mechanisms in ischemia-induced brain damage. Propofol has been shown to attenuate ischemic brain damage via inhibiting neuronal apoptosis. The present study was performed to evaluate the effect of propofol on brain damage and inflammatory reaction in rats of focal cerebral ischemia. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion, then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 h of ischemia. Neurological deficit scores, cerebral infarct size and morphological characteristic were measured 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was assessed 24 h after cerebral ischemia. Nuclear factor-kappa B (NF-?B) p65 expression in ischemic rat brain was detected by western blot. Cyclooxygenase-2 (COX-2) expression in ischemic rat brain was determined by immunohistochemistry. ELISA was performed to detect the serum concentration of tumor necrosis factor-? (TNF-?). Neurological deficit scores, cerebral infarct size and MPO activity were significantly reduced by propofol administration. Furthermore, expression of NF-?B, COX-2 and TNF-? were attenuated by propofol administration. Our results demonstrated that propofol (10 and 50 mg/kg) reduces inflammatory reaction and brain damage in focal cerebral ischemia in rats. Propofol exerts neuroprotection against ischemic brain damage, which might be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory genes. PMID:24610527

Shi, Song-Sheng; Yang, Wei-Zhong; Chen, Ye; Chen, Jian-Ping; Tu, Xian-Kun

2014-05-01

103

MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury  

PubMed Central

Study design Experimental, controlled, animal study. Objectives To use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion. Setting Baltimore. Methods Adult female Long–Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide). Results MRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (P<0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P>0.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (P<0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated with significantly better neurological function (unilateral BBB scores) at 24 h in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral (median scores, 12 vs 2; P<0.001) hindlimbs. Conclusion MRI is an accurate non-invasive imaging biomarker of lesion expansion and is a sensitive measure of the ability of glibenclamide to reduce lesion expansion.

Simard, JM; Popovich, PG; Tsymbalyuk, O; Caridi, J; Gullapalli, RP; Kilbourne, MJ; Gerzanich, V

2014-01-01

104

31P magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure.  

PubMed

STUDY OBJECTIVE - The purpose of the study was to confirm the presence of abnormalities in the coronary vessels of hypertensive hearts, and to examine the effects of reduced coronary perfusion pressure. DESIGN - Rats were made hypertensive by aortic banding, after which coronary flow and myocardial energy metabolites were studied in isolated hearts at physiological (140 cm H2O) and reduced (80 cm H2O) coronary perfusion pressures and compared with normotensive controls. SUBJECTS - Wistar-Kyoto rats between 250 and 300 g were used. Left ventricular hypertrophy was generated by aortic banding in 29 rats; 8 were studied one week after banding, and 21 three weeks after banding. There were 45 controls. MEASUREMENTS and RESULTS - Energy metabolites were assessed using 31P magnetic resonance spectroscopy, standardised by high performance liquid chromatography of rapidly freeze clamped tissue. Left ventricular wall thickness was determined using two dimensional echocardiography. Coronary flow (normalised for heart weight) was reduced significantly after one and three weeks of left ventricular hypertrophy, and at either physiological or below physiological pressures. Hearts from aortic banded animals developed higher intraventricular pressure with reduced oxygen consumption when perfused at a physiological pressure, indicating increased thermodynamic efficiency. When perfused at reduced pressure, the developed pressure declined significantly in both the one week and the three week banded groups compared to normal hearts. The phosphorylation potential and intracellular pH (pHi) were not significantly lower after one week and three weeks of left ventricular hypertrophy when perfused at physiological pressure. When perfused at reduced pressure, phosphorylation potential declined significantly in both groups of hypertrophied hearts, whereas pHi declined significantly only in the three week hypertrophy group. CONCLUSIONS - There is improved thermodynamic efficiency of the hypertrophied myocardium when perfused at a physiological pressure, but when perfused at a reduced pressure, ventricular function, phosphorylation potential and pHi decline in rat hearts after three weeks of aortic constriction, indicating an impairment of coronary reserve. PMID:2139362

Aufferman, W; Wu, S T; Derugin, N; Parmley, W; Higgins, C; Kapelko, V; Wikman-Coffelt, J

1990-01-01

105

Food restriction reduces sympathetic support of blood pressure in spontaneously hypertensive rats.  

PubMed

We tested the hypothesis that food restriction would attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Furthermore, we hypothesized that food restriction would reduce the tonic sympathetic nervous system support of blood pressure in the SHR. Male SHR (Charles River, age 5 wk) were randomly assigned to ad libitum (ADLIB, n = 8) or food-restricted (FR, n = 9) groups. ADLIB rats were given free access to nonpurified diet and demineralized water. Food-restricted rats ate 60% of the amount of nonpurified diet consumed by rats in the ADLIB group. After 8 wk of treatment, ADLIB rats were heavier than FR rats (ADLIB = 318 +/- 4 g; FR = 193 +/- 5 g, P < 0.05). Blood pressure and heart rate (HR) were measured after chronic implantation of iliac arterial and jugular venous catheters. Food-restricted rats had lower mean arterial blood pressure (MAP) than ADLIB rats, measured in conscious, unrestrained state 4-6 h after catheterization (ADLIB = 162 +/- 3 mmHg; FR = 142 +/- 3 mmHg, P < 0.05) and measured on the day after surgery (ADLIB = 150 +/- 6 mmHg; FR = 130 +/- 3 mmHg, P < 0.05). There were no significant differences in resting HR on either day. Food-restricted rats exhibited augmented cardiac baroreflex-mediated bradycardia (bolus phenylephrine, 0.5-4.0 pg/kg intravenously) as assessed by linear slope of the AHR/AMAP relationship (ADLIB = -0.73 beats/(min x mmHg); FR = -1.62 beats/(min x mmHg), P < 0.05). Sympathetic support of blood pressure quantified by the depressor response to ganglionic blockade (hexamethonium 30 mg/kg; atropine 0.1 mg/kg intravenously), was greater in the ADLIB group (ADLIB: -59 +/- 8 mmHg; FR: -36 +/- 2 mmHg, P < 0.05). The results support the hypotheses that chronic food restriction reduces the development of hypertension and sympathetic support of MAP in spontaneously hypertensive rats. PMID:9109619

Overton, J M; VanNess, J M; Casto, R M

1997-04-01

106

Energy Restriction Reduces Fractional Calcium Absorption in Mature Obese and Lean Rats1,2  

PubMed Central

Weight loss is associated with bone loss and the risk may be greater in lean than heavier individuals, but the mechanisms involved remain unclear. We hypothesized that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA) and be mediated by Ca-regulating hormones, but differently in obese and lean rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4 mo. At 6 mo of age, the resulting lean [284 ± 28g (mean ± sd, n = 18)] and obese (319 ± 34g, n = 20) groups (P < 0.005) were divided into controls (CTL, ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin) was lower in obese than in lean rats, whereas Ca balance components and Ca-regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 ± 7% compared with a 6 ± 6% gain in CTL rats (P < 0.001). For both lean and obese rats, TFCA (5-d measurement, 45Ca radioisotope) decreased from 30 ± 9% to 24 ± 9% with EnR, compared with 25 ± 10% to 29 ± 11% in controls (P < 0.05). Weight loss was directly correlated with the decrease in TFCA (r = 0.34, P < 0.05). Uterine weights indicated a reduced estrogenic activity in energy-restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E2) correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25-hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy-restricted rats. Distinct endocrine profiles during weight loss in obese and lean rats suggest that the susceptibility of bone and Ca metabolism to EnR could differ depending on initial body weight.

Cifuentes, Mariana; Morano, Amy B.; Chowdhury, Hasina A.; Shapses, Sue A.

2014-01-01

107

Hyperbaric oxygen pretreatment reduces the incidence of decompression sickness in rats.  

PubMed

We have previously hypothesised that the number of bubbles evolving during decompression from a dive, and therefore the incidence of decompression sickness (DCS), might be reduced by pretreatment with hyperbaric oxygen (HBO). The inert gas in the gas micronuclei would be replaced by oxygen, which would subsequently be consumed by the mitochondria. This has been demonstrated in the transparent prawn. To investigate whether our hypothesis holds for mammals, we pretreated rats with HBO at 304, 405, or 507 kPa for 20 min, after which they were exposed to air at 1,013 kPa for 33 min and decompressed at 202 kPa/min. Twenty control rats were exposed to air at 1,013 kPa for 32 min, without HBO pretreatment. On reaching the surface, the rat was immediately placed in a rotating cage for 30 min. The animal's behaviour enabled us to make an early diagnosis of DCS according to accepted symptoms. Rats were examined again after 2 and 24 h. After 2 h, 65% of the control rats had suffered DCS (45% were dead), whereas 35% had no DCS. HBO pretreatment at 304, 405 and 507 kPa significantly reduced the incidence of DCS at 2 h to 40, 40 and 35%, respectively. Compared with the 45% mortality rate in the control group after 24 h, in all of the pretreated groups this was 15%. HBO pretreatment is equally effective at 304, 405 or 507 kPa, bringing about a significant reduction in the incidence of DCS in rats decompressed from 1,013 kPa. PMID:17674026

Katsenelson, Ksenya; Arieli, Yehuda; Abramovich, Amir; Feinsod, Moshe; Arieli, Ran

2007-11-01

108

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

PubMed Central

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.

2014-01-01

109

Hyperbaric oxygen preconditioning reduces the incidence of decompression sickness in rats via nitric oxide.  

PubMed

Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect. PMID:20568547

Fan, Dan-Feng; Liu, Kan; Xu, Wei-Gang; Zhang, Rong-Jia; Liu, Yun; Kang, Zhi-Min; Sun, Xue-Jun; Li, Run-Ping; Tao, Heng-Yi; Zhang, Jian-Lin

2010-01-01

110

Aerobic endurance training reduces bubble formation and increases survival in rats exposed to hyperbaric pressure  

PubMed Central

The formation of bubbles is the basis for injury to divers after decompression, a condition known as decompression illness. In the present study we investigated the effect of endurance training in the rat on decompression-induced bubble formation. A total of 52 adult female Sprague-Dawley rats (300-370 g) were randomly assigned to one of two experimental groups: training or sedentary control. Trained rats exercised on a treadmill for 1.5 h per day for 1 day, or for 2 or 6 weeks (5 days per week) at exercise intervals that alternated between 8 min at 85-90 % of maximal oxygen uptake (V?O2,max) and 2 min at 50-60 % of V?O2,max. Rats were compressed (simulated dive) in a decompression chamber in pairs, one sedentary and one trained, at a rate of 200 kPa min?1 to a pressure of 700 kPa, and maintained for 45 min breathing air. At the end of the exposure period, rats were decompressed linearly to the ‘surface’ (100 kPa) at a rate of 50 kPa min?1. Immediately after reaching the ‘surface’ (100 kPa) the animals were anaesthetized and the right ventricle was insonated using Doppler ultrasound. Intensity-controlled interval training significantly increased V?O2,max by 12 and 60 % after 2 and 6 weeks, respectively. At 6 weeks, left and right ventricular weights were 14 and 17 % higher, respectively, in trained compared to control rats. No effect of training was observed on skeletal muscle weight. Bubble formation was significantly reduced in trained rats after both 2 and 6 weeks. However, the same effect was seen after a single bout of aerobic exercise lasting 1.5 h on the day prior to decompression. All of the rats that exercised for 1.5 h and 2 weeks, and most of those that trained for 6 weeks, survived the protocol, whereas most sedentary rats died within 60 min post-decompression. This study shows that aerobic exercise protects rats from severe decompression and death. This may be a result of less bubbling in the trained animals. The data showed that the increase in aerobic capacity per se was not the main mechanism, but rather an acute effect that was most notable 20 h after a single, or the last, exercise bout, with less effect after 48 h.

Wisl?ff, Ulrik; Brubakk, Alf O

2001-01-01

111

Chronic psychostimulant exposure to adult, but not periadolescent rats reduces subsequent morphine antinociception.  

PubMed

Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced sensitivity to opioids. Two important questions are whether this enhancement is specific to the age of psychostimulant exposure and the type of psychostimulant. To answer these questions periadolescent (PD 35) and adult (PD 55) rats received daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive days. Two weeks later, acute morphine antinociception was assessed on the hot plate using a cumulative dose response procedure. Following acute antinociceptive testing, morphine tolerance was induced in half the animals by administering morphine twice a day over 2 days. Rats pretreated with MPH and METH during the periadolescent period of ontogeny showed no change in acute morphine antinociception, but rats exposed to a relatively high METH dose (3 mg/kg) displayed enhanced morphine tolerance compared to saline pretreated controls. MPH and METH pretreatment during adulthood led to a reduction in morphine antinociceptive potency and an apparent reduction in morphine tolerance. When combined with our previously published findings, these data indicate that the developmental stage during which MPH and METH exposure occurs differentially alters adult morphine responsiveness. That is, psychostimulant exposure to preweanling rats enhances morphine antinociception and facilitates the development of tolerance, whereas psychostimulant exposure to adult rats reduces subsequent morphine antinociception and tolerance. These alterations indicate that it could be important for physicians to know about prior psychostimulant use when prescribing opioids for pain relief. PMID:22405777

Cyr, Michelle C; Ingram, Susan L; Aicher, Sue A; Morgan, Michael M

2012-06-01

112

Chronic psychostimulant exposure to adult, but not periadolescent rats reduces subsequent morphine antinociception  

PubMed Central

Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced sensitivity to opioids. Two important questions are whether this enhancement is specific to the age of psychostimulant exposure and the type of psychostimulant. To answer these questions periadolescent (PD 35) and adult (PD 55) rats received daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive days. Two weeks later, acute morphine antinociception was assessed on the hot plate using a cumulative dose response procedure. Following acute antinociceptive testing, morphine tolerance was induced in half the animals by administering morphine twice a day over two days. Rats pretreated with MPH and METH during the periadolescent period of ontogeny showed no change in acute morphine antinociception, but rats exposed to a relatively high METH dose (3 mg/kg) displayed enhanced morphine tolerance compared to saline pretreated controls. MPH and METH pretreatment during adulthood led to a reduction in morphine antinociceptive potency and an apparent reduction in morphine tolerance. When combined with our previously published findings, these data indicate that the developmental stage during which MPH and METH exposure occurs differentially alters adult morphine responsiveness. That is, psychostimulant exposure to preweanling rats enhances morphine antinociception and facilitates the development of tolerance, whereas psychostimulant exposure to adult rats reduces subsequent morphine antinociception and tolerance. These alterations indicate that it could be important for physicians to know about prior psychostimulant use when prescribing opioids for pain relief.

Cyr, Michelle C; Ingram, Susan L.; Aicher, Sue A.; Morgan, Michael M

2012-01-01

113

Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats.  

PubMed

The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350 +/- 50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat, i.e., n=32) two of which were made diabetic (given alloxan i.v. 30 mg/kg). Group 1 was used to measure the permeation of MKC (50 microg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200 microg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p < 0.01) and increased its secretory flux (p < 0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter. PMID:19462928

Al-Salami, Hani; Butt, Grant; Tucker, Ian; Fawcett, Paul J; Golocorbin-Kon, Svetlana; Mikov, Ivan; Mikov, Momir

2009-01-01

114

Reduced expression of insulin receptors in the kidneys of insulin-resistant rats.  

PubMed

Insulin resistance is accompanied by hyperinsulinemia and activation of the renin-angiotensin system, both of which are associated with hypertension. Because the kidney plays a major role in the regulation of blood pressure, we studied the regulation of insulin receptor expression in the kidney during states of insulin resistance. Using two rat models of insulin resistance, Western blot analysis demonstrated a significant reduction in the expression of insulin receptor subunits in the kidney compared to lean control rats. Treatment of insulin resistance in Zucker rats with the insulin-sensitizing drug rosiglitazone partially restored renal insulin receptor levels. Conversely, treatment with the angiotensin II type 1 receptor (AT1) antagonist candesartan increased renal insulin receptor expression compared to untreated rats. Streptozotocin-induced hyperglycemia, which results from hypoinsulinemia, reduced expression of renal insulin receptors. Hyperinsulinemia induced by insulin infusion, however, did not produce a similar effect. In conclusion, insulin receptors are downregulated in the kidneys of insulin resistant rats, possibly mediated by hyperglycemia and angiotensin II. PMID:17855644

Tiwari, Swasti; Halagappa, Veerendra K M; Riazi, Shahla; Hu, Xinqun; Ecelbarger, Carolyn A

2007-10-01

115

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

PubMed

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

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

116

Pulsed electromagnetic field stimulates osteoprotegerin and reduces RANKL expression in ovariectomized rats.  

PubMed

Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor ?B ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17?-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG. PMID:22948539

Zhou, Jun; Chen, Shiju; Guo, Hua; Xia, Lu; Liu, Huifang; Qin, Yuxi; He, Chengqi

2013-05-01

117

Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.  

PubMed

Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. PMID:23956805

Ostrowski, Robert P; Schulte, Reinhard W; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S; Zhang, John H

2012-12-01

118

Acute Splenic Irradiation Reduces Brain Injury in the Rat Focal Ischemic Stroke Model  

PubMed Central

Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen’s inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain.

Ostrowski, Robert P.; Schulte, Reinhard W.; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S.; Zhang, John H.

2013-01-01

119

Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats  

PubMed Central

OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3? (GSK-3?). Here, we investigate the role of GSK-3? inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusion of common carotid arteries followed by 1 or 24 h of reperfusion. Insulin (2–12 IU/kg i.v.) or the selective GSK-3? inhibitor TDZD-8 (0.2–3 mg/kg i.v.) was administered during reperfusion. RESULTS—Insulin or TDZD-8 dramatically reduced infarct volume and levels of S100B protein, a marker of cerebral injury. Both drugs induced phosphorylation of the Ser9 residue, thereby inactivating GSK-3? in the rat hippocampus. Insulin, but not TDZD-8, lowered blood glucose. The hippocampi of the drug-treated animals displayed reduced oxidative stress at 1 h of reperfusion as shown by the decreased generation of reactive oxygen species and lipid peroxidation. I/R-induced activation of nuclear factor-?B was attenuated by both drug treatments. At 24 h of reperfusion, TDZD-8 and insulin significantly reduced plasma levels of tumor necrosis factor-?; neutrophil infiltration, measured as myeloperoxidase activity and intercellular-adhesion-molecule-1 expression; and cyclooxygenase-2 and inducible-NO-synthase expression. CONCLUSIONS—Acute administration of insulin or TDZD-8 reduced cerebral I/R injury in diabetic rats. We propose that the inhibitory effect on the activity of GSK-3? contributes to the protective effect of insulin independently of any effects on blood glucose.

Collino, Massimo; Aragno, Manuela; Castiglia, Sara; Tomasinelli, Chiara; Thiemermann, Christoph; Boccuzzi, Giuseppe; Fantozzi, Roberto

2009-01-01

120

IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat  

PubMed Central

Recent studies suggest an inflammatory process, characterized by local cytokine/chemokine production and immune cell infiltration, regulates islet dysfunction and insulin resistance in type 2 diabetes. However, the factor initiating this inflammatory response is not known. Here, we characterized tissue inflammation in the type 2 diabetic GK rat with a focus on the pancreatic islet and investigated a role for IL-1. GK rat islets, previously characterized by increased macrophage infiltration, displayed increased expression of several inflammatory markers including IL-1?. In the periphery, increased expression of IL-1? was observed primarily in the liver. Specific blockade of IL-1 activity by the IL-1 receptor antagonist (IL-1Ra) reduced the release of inflammatory cytokines/chemokines from GK islets in vitro and from mouse islets exposed to metabolic stress. Islets from mice deficient in IL-1? or MyD88 challenged with glucose and palmitate in vitro also produced significantly less IL-6 and chemokines. In vivo, treatment of GK rats with IL-1Ra decreased hyperglycemia, reduced the proinsulin/insulin ratio, and improved insulin sensitivity. In addition, islet-derived proinflammatory cytokines/chemokines (IL-1?, IL-6, TNF?, KC, MCP-1, and MIP-1?) and islet CD68+, MHC II+, and CD53+ immune cell infiltration were reduced by IL-1Ra treatment. Treated GK rats also exhibited fewer markers of inflammation in the liver. We conclude that elevated islet IL-1? activity in the GK rat promotes cytokine and chemokine expression, leading to the recruitment of innate immune cells. Rather than being directly cytotoxic, IL-1? may drive tissue inflammation that impacts on both ? cell functional mass and insulin sensitivity in type 2 diabetes.

Ehses, J. A.; Lacraz, G.; Giroix, M.-H.; Schmidlin, F.; Coulaud, J.; Kassis, N.; Irminger, J.-C.; Kergoat, M.; Portha, B.; Homo-Delarche, F.; Donath, M. Y.

2009-01-01

121

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

PubMed Central

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.

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

122

Probiotic Pre-treatment Reduces Gliclazide Permeation (ex vivo) in Healthy Rats but Increases It in Diabetic Rats to the Level Seen in Untreated Healthy Rats  

PubMed Central

Aim To investigate the influence of probiotic pre-treatment on the permeation of the antidiabetic drug gliclazide in healthy and diabetic rats. Methods Wistar rats (age 2–3 months, weight 350 ± 50 g) were randomly allocated into one of 4 groups (N = 16 each group): healthy control, healthy probiotic, diabetic control, and diabetic probiotic. Probiotics (75 mg/kg, equal quantities of Lactobacillus acidophilus, Bifidobacterium lactis, and Lactobacillus rhamnosus) were administered twice a day for three days to the appropriate groups after diabetes had been induced with alloxan i.v. 30 mg/kg. Rats were sacrificed, ileal tissues mounted in Ussing chambers and gliclazide (200 µg/mL) was administered for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. Results Treatment of healthy rats with probiotics reduced Jss(MtoS) of gliclazide from 1.2 ± 0.3 to 0.3 ± 0.1 µg/min/cm2 (P < 0.01) and increased Jss(StoM)from 0.6 ± 0.1 to 1.4 ± 0.3 (P < 0.01) resulting in net secretion while, in diabetic tissues, treatment with probiotics increased both Jss(MtoS) and Jss(StoM)fluxes of gliclazide to the comparable levels of healthy tissues resulting in net absorption. Discussion In healthy rats, the reduction in Jss(MtoS) after probiotics administration could be explained by the production of bacterial metabolites that upregulate the mucosal efflux drug transporters Mrp2 that control gliclazide transport. In diabetic rats, the restored fluxes of gliclazide after probiotic treatment, suggests the normalization of the functionality of the drug transporters resulting in a net absorption. Conclusion Probiotics may alter gliclazide transport across rat ileal tissue studied ex vivo.

Al-Salami, Hani; Butt, Grant; Tucker, Ian; Skrbic, Ranko; Golocorbin-Kon, Svetlana; Mikov, Momir

2008-01-01

123

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

Microsoft Academic Search

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

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

2011-01-01

124

TNF? siRNA reduces brain TNF and EEG delta wave activity in rats  

Microsoft Academic Search

Tumor necrosis factor alpha (TNF?) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNF? were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNF? siRNA treatment specifically reduced TNF? mRNA by 45% in vitro without affecting interleukin-6

Ping Taishi; Lynn Churchill; Mingxiang Wang; Daniel Kay; Christopher J. Davis; Xin Guan; Alok De; Tadanobu Yasuda; Fan Liao; James M. Krueger

2007-01-01

125

Enalapril Prevents Imminent and Reduces Manifest Cerebral Edema in Stroke-Prone Hypertensive Rats  

Microsoft Academic Search

Background and Purpose—Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl intake, show severe hypertension, organ damage, and early death. Preventive treatment with an angiotensin-converting enzyme (ACE) inhibitor is known to reduce mortality. Previously we found that proteinuria always precedes cerebral edema in SHRSP. Hence, in this study ACE inhibition was started later, ie, directly after manifestation of either proteinuria

Erwin L. A. Blezer; Klaas Nicolay; P. R. Dop Bar; Roel Goldschmeding; Gerard H. Jansen; Hein A. Koomans; Jaap A. Joles

126

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

Microsoft Academic Search

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

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

2003-01-01

127

Reduced bone perfusion in osteoporosis: likely causes in an ovariectomy rat model.  

PubMed

Purpose: To investigate the cause of reduced vertebral perfusion in a rat ovariectomy model. Materials and Methods: Experimental protocol was approved by the local Animal Experiment Ethics Committee. Twenty-two Sprague-Dawley rats were studied. Computed tomographic bone densitometry and magnetic resonance perfusion imaging were performed at baseline and 2, 4, and 8 weeks after ovariectomy (n = 11) or sham surgery (n = 11). Perfusion parameters analyzed were maximum enhancement (E(max)) and enhancement slope (E(slope)). After the animals were sacrificed, the aorta and femoral artery were analyzed for vessel reactivity, and the lumbar vertebrae were analyzed for marrow content. Results: In control rats, bone mineral density (BMD), E(max), and E(slope) remained constant. In ovariectomy rats, a comparable reduction in BMD and the perfusion parameters at two weeks post-ovariectomy (BMD, 9.3%; E(max), 11.6%; E(slope), 9%) was seen 2 weeks after ovariectomy, and further reductions were seen 4 weeks (BMD, 17.5%; E(max), 15.6%; E(slope), 33%) and 8 weeks (BMD, 18.8%; E(max), 14.2%; E(slope), 33%) after ovariectomy. Endothelial dysfunction was observed in both the aorta and femoral artery of the ovariectomy group but not of the control group. Increased marrow fat area was seen in the ovariectomy group (52.9% vs 21.6%; P < .01) owing to an increase in fat cell number. Decreased erythropoetic marrow area (32.5% vs 48.6%; P < .05) was also observed in the ovariectomy group. Conclusion: Reduced bone perfusion occurs in synchrony with reduced BMD. The most likely causes of reduced bone perfusion are a reduction in the amount of erythropoetic marrow and endothelial dysfunction after ovariectomy. (c) RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090608/-/DC1. PMID:20177089

Griffith, James F; Wang, Yi-Xiang J; Zhou, Hua; Kwong, Wing Hang; Wong, Wing Tak; Sun, Yan-Lin; Huang, Yu; Yeung, David K W; Qin, Ling; Ahuja, Anil T

2010-03-01

128

Blockade of 5HT 7 receptors reduces tactile allodynia in the rat  

Microsoft Academic Search

This study assessed the role of systemic and spinal 5-HT7 receptors on rats submitted to spinal nerve injury. In addition, the 5-HT7 receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5\\/L6 spinal nerve ligation. Systemic (0.01–10mg\\/kg) or spinal (0.3–30?g) administration of the selective 5-HT7 receptor antagonist SB-269970 but not vehicle reduced

Evelyn Amaya-Castellanos; Jorge B. Pineda-Farias; Gabriela Castañeda-Corral; Guadalupe C. Vidal-Cantú; Janet Murbartián; Héctor I. Rocha-González; Vinicio Granados-Soto

2011-01-01

129

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

Microsoft Academic Search

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

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

2008-01-01

130

Interaction of tonic neck and vestibular reflexes in the forelimb of the decerebrate cat  

Microsoft Academic Search

Summary  Tonic neck reflexes, studied with EMG recording, have similar dynamics in forelimb extensor muscles of acutely labyrinthectomized cats, and in cats with intact labyrinths. The reflex occurs more frequently in the latter and its gain is higher. In intact preparations we evoked vestibular and tonic neck reflexes separately or in combination, at frequencies of 0.05–0.5 Hz. As expected from earlier

K. Ezure; V. J. Wilson

1984-01-01

131

Cineradiographic study of forelimb movements during quadrupedal walking in the brown lemur (Eulemur fulvus, Primates: Lemuridae).  

PubMed

Movements of forelimb joints and segments during walking in the brown lemur (Eulemur fulvus) were analyzed using cineradiography (150 frames/sec). Metric gait parameters, forelimb kinematics, and intralimb coordination are described. Calculation of contribution of segment displacements to stance propulsion shows that scapular retroversion in a fulcrum near the vertebral border causes more than 60% of propulsion. The contribution by the shoulder joint is 30%, elbow joint 5%, and wrist joint 1%. Correlation analysis was applied to reveal the interdependency between metric and kinematic parameters. Only the effective angular movement of the elbow joint during stance is speed-dependent. Movements of all other forelimb joints and segments are independent of speed and influence, mainly, linear gait parameters (stride length, stance length). Perhaps the most important result is the hitherto unknown and unexpected degree of scapular mobility. Scapular movements consist of ante-/retroversion, adduction/abduction, and scapular rotation about the longitudinal axis. Inside rotation of the scapula (60 degrees -70 degrees ), together with flexion in the shoulder joint, mediates abduction of the humerus, which is not achieved in the shoulder joint, and is therefore strikingly different from humeral abduction in man. Movements of the shoulder joint are restricted to flexion and extension. At touch down, the shoulder joint of the brown lemur is more extended compared to that of other small mammals. The relatively long humerus and forearm, characteristic for primates, are thus effectively converted into stride length. Observed asymmetries in metric and kinematic behavior of the left and right forelimb are caused by an unequal lateral bending of the spinal column. PMID:10640950

Schmidt, M; Fischer, M S

2000-02-01

132

Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury  

PubMed Central

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.

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

2013-01-01

133

The prevalence and risk factors associated with forelimb skin abrasions and sole bruising in preweaning piglets  

Microsoft Academic Search

The presence of skin abrasions and sole bruising in 264 preweaning piglets (1–30 days old) from 13 breeding units in south west England was investigated in 1995. The mean prevalence of forelimb skin abrasions among the pigs on the study farms was 36% (range 0–59%) and sole bruising was 50% (range 0–95%). Skin abrasions were located on three aspects on

N. Mouttotou; F. M. Hatchell; L. E. Green

1999-01-01

134

Alginate enhances excretion and reduces absorption of strontium and cesium in rats.  

PubMed

Alginate (ALA), which is an intercellular polysaccharide associated with brown algae, is used as a food additive, a health food and a medicine. Here, we first examined the adsorption of strontium (Sr) and cesium (Cs) by ALA in vitro, and then evaluated the effects of ALA on absorption and excretion of Sr and Cs in rats, in order to evaluate its potential usefulness for minimizing radiation damage from materials released after a nuclear accident. Both Sr and Cs were concentration-dependently adsorbed by sodium alginate (ALA-Na) in vitro. In rats given diet containing either ALA-Na or calcium alginate (ALA-Ca) for two weeks, the plasma concentration of Sr gradually decreased compared with the controls (normal diet); however, in the case of Cs, the plasma concentration was decreased only in the ALA-Ca group, but not the ALA-Na group. Moreover, we examined the effect of preadministration of diet containing either ALA-Na or ALA-Ca on absorption of Sr and Cs administered orally as the chloride salts to rats. Absorption of both Sr and Cs was reduced in the ALA-Ca group, while absorption of only Sr was reduced in the ALA-Na group. Safety assessments indicated that ALA-Ca is safer than ALA-Na. These results indicate that ALA-Ca reduces absorption and promotes excretion of both Sr and Cs, while ALA-Na does so only for Sr. PMID:23318531

Idota, Yoko; Harada, Hitomi; Tomono, Takumi; Morimoto, Kaori; Kobayashi, Shoko; Kakinuma, Chihaya; Miyajima, Chihiro; Kasahara, Fumiyoshi; Ogihara, Takuo

2013-01-01

135

Disruption of footshock-induced theta rhythms by stimulating median raphe nucleus reduces anxiety in rats.  

PubMed

Theta rhythms generated in the hippocampus are controlled by the pacemaker in the medial septum-diagonal band of Broca (MS-DBB). The median raphe nucleus (MRN) transmits serotonergic signals to the MS-DBB, which suppresses the septo-hippocampus-produced theta waves, whereas GABAergic interneurons in the MRN facilitate the generation of theta oscillations. Animal studies have indicated that fear increases theta oscillations. Moreover, anxiolytics reduce reticular formation-elicited theta rhythms and theta blockade decreases anxiety. In this study, we hypothesized that the MRN mediates anxiety reduction caused by the theta blockade. Our results demonstrated that inescapable-footshock stimulation significantly increased the power of low-frequency theta oscillations (4-7 Hz) in rats. Both the electrical stimulation of MRN and administration of bicuculline into the MRN successfully desynchronized footshock-induced theta oscillations. Compared to the naïve rats, inescapable-footshock stimulation diminished the entry percentage and time spent in the open arms of the elevated plus maze (EPM), behavioral indicators of anxiety. Rats treated with either MRN stimulation or bicuculline administration to desynchronize theta oscillations reduced anxiety caused by the inescapable-footshock stimulation. Our results demonstrated that the electrical stimulation of MRN or blockade of the GABAergic pathways in the MRN interferes with theta oscillations and reduces anxiety, implicating the role of MRN. PMID:23542088

Hsiao, Yi-Tse; Yi, Pei-Lu; Cheng, Chiung-Hsiang; Chang, Fang-Chia

2013-06-15

136

Low-Anxiety Rat Phenotypes Can Be Further Reduced through Genetic Intervention  

PubMed Central

Background A previous study using an intercross between the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) identified a locus on chromosome 4, named Anxrr16, influencing an experimental index of anxiety and showing a transgressive effect, with alleles from the LEW strain (more anxious) decreasing rather than increasing anxiety. Objective To confirm the location and isolate the effect of a rat genome region named Anxrr16 through a planned genomic recombination strategy, where the target locus in SHR rats was replaced with LEW genetic material. Methods A new congenic strain, named SHR.LEW-Anxrr16 (SLA16), was developed from a cross between LEW (donor) and SHR (receptor) rats and then evaluated in several anxiety-related tests. The activity and attention levels of the new strain were also evaluated, since hyperactivity was observed during its construction and because SHR is a model of attention deficit hyperactivity disorder. Results Significant effects of Anxrr16 were found for open field central locomotion, as well as for other indices of anxiety from the light/dark box, triple test and T-maze. In all cases, the low-anxiety levels of SHR rats were further reduced by the insertion of LEW alleles. Differences in locomotor activity were found only in unfamiliar (hence stressful) environments and no genetic effects were observed in indices of attention. Conclusion The SLA16 strain can help in the identification of the molecular pathways involved in experimental anxiety and it demonstrates how apparently extreme phenotypes sometimes hide major opposite-acting genes.

Granzotto, Natalli; Ramos, Andre

2013-01-01

137

Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb.  

PubMed

To date, only the five most posterior groups of Hox genes, Hox9-Hox13, have demonstrated loss-of-function roles in limb patterning. Individual paralog groups control proximodistal patterning of the limb skeletal elements. Hox9 genes also initiate the onset of Hand2 expression in the posterior forelimb compartment, and collectively, the posterior HoxA/D genes maintain posterior Sonic Hedgehog (Shh) expression. Here we show that an anterior Hox paralog group, Hox5, is required for forelimb anterior patterning. Deletion of all three Hox5 genes (Hoxa5, Hoxb5, and Hoxc5) leads to anterior forelimb defects resulting from derepression of Shh expression. The phenotype requires the loss of all three Hox5 genes, demonstrating the high level of redundancy in this Hox paralogous group. Further analyses reveal that Hox5 interacts with promyelocytic leukemia zinc finger biochemically and genetically to restrict Shh expression. These findings, along with previous reports showing that point mutations in the Shh limb enhancer lead to similar anterior limb defects, highlight the importance of Shh repression for proper patterning of the vertebrate limb. PMID:24218595

Xu, Ben; Hrycaj, Steven M; McIntyre, Daniel C; Baker, Nicholas C; Takeuchi, Jun K; Jeannotte, Lucie; Gaber, Zachary B; Novitch, Bennett G; Wellik, Deneen M

2013-11-26

138

Elbow joint adductor moment arm as an indicator of forelimb posture in extinct quadrupedal tetrapods.  

PubMed

Forelimb posture has been a controversial aspect of reconstructing locomotor behaviour in extinct quadrupedal tetrapods. This is partly owing to the qualitative and subjective nature of typical methods, which focus on bony articulations that are often ambiguous and unvalidated postural indicators. Here we outline a new, quantitatively based forelimb posture index that is applicable to a majority of extant tetrapods. By determining the degree of elbow joint adduction/abduction mobility in several tetrapods, the carpal flexor muscles were determined to also play a role as elbow adductors. Such adduction may play a major role during the stance phase in sprawling postures. This role is different from those of upright/sagittal and sloth-like creeping postures, which, respectively, depend more on elbow extensors and flexors. Our measurements of elbow muscle moment arms in 318 extant tetrapod skeletons (Lissamphibia, Synapsida and Reptilia: 33 major clades and 263 genera) revealed that sprawling, sagittal and creeping tetrapods, respectively, emphasize elbow adductor, extensor and flexor muscles. Furthermore, scansorial and non-scansorial taxa, respectively, emphasize flexors and extensors. Thus, forelimb postures of extinct tetrapods can be qualitatively classified based on our quantitative index. Using this method, we find that Triceratops (Ceratopsidae), Anhanguera (Pterosauria) and desmostylian mammals are categorized as upright/sagittally locomoting taxa. PMID:22357261

Fujiwara, Shin-ichi; Hutchinson, John R

2012-07-01

139

The phylogeny of the red panda (Ailurus fulgens): evidence from the forelimb.  

PubMed

Within the order Carnivora, the phylogeny of the red panda (Ailurus fulgens) is contentious, with morphological and molecular studies supporting a wide range of possible relationships, including close ties to procyonids, ursids, mustelids and mephitids. This study provides additional morphological data, including muscle maps, for the forelimb of Ailurus, based on the dissection of four cadavers from the National Zoological Park, Washington, DC, USA. The red panda forelimb is characterized by a number of primitive features, including the lack of m. rhomboideus profundus, a humeral insertion for m. cleidobrachialis, the presence of mm. brachioradialis, articularis humeri and coracobrachialis, a single muscle belly for m. extensor digitorum lateralis with tendons to digits III-V, four mm. lumbricales, and the presence of mm. flexor digitorum brevis manus, adductores digiti I, II and V, and abductor digiti I and V. Red pandas resemble Ailuropoda, mustelids and some procyonids in possessing a soft tissue origin of m. flexor digitorum superficialis. In addition, red pandas are similar to ursids and procyonids in having a variable presence of m. biceps brachii caput breve. Furthermore, Ailurus and some ursids lack m. rhomboideus capitis. The forelimb muscle maps from this study represent a valuable resource for analyzing the functional anatomy of fossil ailurids and some notes on the Miocene ailurid, Simocyon batalleri, are presented. PMID:19930516

Fisher, Rebecca E; Adrian, Brent; Barton, Michael; Holmgren, Jennifer; Tang, Samuel Y

2009-12-01

140

Forelimb anatomy of New World monkeys: myology and the interpretation of primitive anthropoid models.  

PubMed

The forelimbs of 12 genera of New World monkeys, two genera of Old World monkeys, and a gibbon were dissected. Of the 54 muscles examined, 19 exhibited significant intergeneric variation. We present arguments for which morphologies are primitive and which are derived within platyrrhines and within anthropoids. We conclude that the forelimbs of Cebus apella and Callicebus moloch represent good models of the ancestral anthropoid morphology. Thus among living anthropoids they are most appropriate for comparisons with early fossil anthropoids. They are also useful for determining whether myological anomalies of human aneuploids are atavistic. Wagner tree analyses were conducted to assess the value of these myological characters in phylogenetic studies of platyrrhines. In most respects the Wagner trees were consonant with phylogenies previously proposed, although some hypothesized trees are less parsimonious than others in explaining our data. There is an unexpected number of derived features shared by Aotus and the Atelines. There are marked dissimilarities in forelimb musculature between Aotus and Callicebus. PMID:3936364

Dunlap, S S; Thorington, R W; Aziz, M A

1985-12-01

141

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

PubMed

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

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

2012-09-10

142

Reduced expression of Kir6.2/SUR2A subunits explains KATP deficiency in K+-depleted rats.  

PubMed

We investigated on the mechanism responsible for the reduced ATP-sensitive K(+)(K(ATP)) channel activity recorded from skeletal muscle of K(+)-depleted rats. Patch-clamp and gene expression measurements of K(ATP) channel subunits were performed. A down-regulation of the K(ATP) channel subunits Kir6.2(-70%) and SUR2A(-46%) in skeletal muscles of K(+)-depleted rats but no changes in the expression of Kir6.1, SUR1 and SUR2B subunits were observed. A reduced K(ATP) channel currents of -69.5% in K(+)-depleted rats was observed. The Kir6.2/SUR2A-B agonist cromakalim showed similar potency in activating the K(ATP) channels of normokalaemic and K(+)-depleted rats but reduced efficacy in K(+)-depleted rats. The Kir6.2/SUR1-2B agonist diazoxide activated K(ATP) channels in normokalaemic and K(+)-depleted rats with equal potency and efficacy. The down-regulation of the Kir6.2 explains the reduced K(ATP) channel activity in K(+)-depleted rats. The lower expression of SUR2A explains the reduced efficacy of cromakalim; preserved SUR1 expression accounts for the efficacy of diazoxide. Kir6.2/SUR2A deficiency is associated with impaired muscle function in K(+)-depleted rats and in hypoPP. PMID:17825556

Tricarico, Domenico; Mele, Antonietta; Liss, Birgit; Ashcroft, Frances M; Lundquist, Andrew L; Desai, Reshma R; George, Alfred L; Conte Camerino, Diana

2008-01-01

143

Imaging optical reflectance in rodent barrel and forelimb sensory cortex.  

PubMed

Novel neuroimaging techniques are extending the scope for studying dynamic brain function. We have developed a system which enables the repeatable imaging of rapid function in rodent primary somatosensory cortex (S-I), based on activity-related changes in its optical reflectance (intrinsic signals). The S-I cortices of anesthetized male Sprague-Dawley rats were exposed. Images were acquired with a slow-scan, cooled, charge-coupled device camera (CCD) through filters at 550, 610, and 850 nm before, during, and after contralateral stimulation (vibrissal deflection or forepaw stimulation). Images were divided by prestimulus controls and then averaged across 9-27 trials to produce maps of stimulus-related reflectance change. Optical activity had magnitude 10(-3) of baseline reflectance and consistently comprised two distinct spatiotemporal components over cortex, depending on paradigm. The diffuse signal at 610 nm begins 0.5-1 s after stimulus onset and has a duration of 4-5 s. The second signal is macrovenous and is delayed by 1 s. Similar response patterns were observed at 550 and 850 nm. Evoked potentials, recorded at sites inside and outside the zone of optical activity, confirmed the functional nature of these signals. Using a CCD we have imaged functional reflectance changes over rodent S-I which commence, peak, and extinguish over a time scale of seconds. This optical activity is consistent with the etiologies of microvascular recruitment and chromophore redox change. PMID:9343569

Narayan, S M; Santori, E M; Blood, A J; Burton, J S; Toga, A W

1994-06-01

144

Sleeve Gastrectomy in Rats Improves Post-Prandial Lipid Clearance by Reducing Intestinal Triglyceride Secretion  

PubMed Central

Background & Aims Post-prandial hyperlipidemia is a risk factor for atherosclerotic heart disease and is associated with the consumption of high-fat diets and obesity. Bariatric surgeries result in superior and more durable weight loss than dieting. These surgeries are also associated with multiple metabolic improvements, including reduced plasma lipid levels. We investigated whether the beneficial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight-independent. Methods VSG was performed on Long-Evans rats with diet-induced obesity and pair-fed and ad libitum-fed rats that received sham operations (controls). We measured fasting and post-prandial levels of plasma lipid. To determine hepatic and intestinal triglyceride secretion, we injected the lipase inhibitor poloxamer 407 alone, or before oral lipid gavage. 13C-Triolein was used to estimate post-prandial uptake of lipid in the intestine. Results Rats that received VSG and high-fat diets (HFDs) had markedly lower fasting levels of plasma triglyceride, cholesterol, and phospholipid than obese and lean (pair-fed) controls that were fed HFD. Rats that received VSG had a marked, weight-independent reduction in secretion of intestinal triglycerides. VSG did not alter total intestinal triglyceride levels or size of the cholesterol storage pool, nor did it affect the expression of genes in the intestine that control triglyceride metabolism and synthesis . VSG did not affect fasting secretion of triglyceride, liver weight, hepatic lipid storage, or transcription of genes that regulate hepatic lipid processing. Conclusions VSG reduced post-prandial levels of plasma lipid, independently of body weight. This resulted from reduced intestinal secretion of triglycerides following ingestion of a lipid meal and indicates that VSG has important effects on metabolism.

Stefater, MA; Sandoval, DA; Chambers, AP; Wilson-Perez, HE; Hofmann, SM; Jandacek, R; Tso, P; Woods, SC; Seeley, RJ

2011-01-01

145

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

Microsoft Academic Search

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

Louise H. Greenberg; Benjamin Weiss

1978-01-01

146

Ingestion of chilli pepper (Capsicum annuum) reduces salicylate bioavailability after oral asprin administration in the rat.  

PubMed

The bioavailabilities of aspirin (acetylsalicylic acid) and of salicylic acid were studied in male Wistar rats after acute and chronic administration of a Capsicum annuum extract, containing 100 mg of capsaicin per gram. With a single administration of 100 mg/kg of the extract, aspirin blood levels remained unchanged, but salicylic acid bioavailability was reduced in 44% compared with control animals. With a single administration of 300 mg/kg of the extract, aspirin blood levels were undetectable while salicylic acid bioavailability was reduced in 59%. Chronic administration once daily for 4 weeks of 100 and 300 mg/kg of the extract resulted in undetectable aspirin blood levels, while salicylic acid bioavailability was reduced in 63 and 76%, respectively, compared with controls. Results show that Capsicum ingestion reduces oral drug bioavailability, likely as a result of the gastrointestinal effects of capsaicin. PMID:10537230

Cruz, L; Castañeda-Hernández, G; Navarrete, A

1999-06-01

147

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

PubMed

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

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

2010-04-01

148

[Dietary SkQ1 supplement reduces myocardial ischemia- reperfusion injury in rats in vivo].  

PubMed

To examine whether nutritional supplementation with SkQ1 can reduce myocardial ischemia-reperfusion injury in vivo, Wistar rats were fed a regular diet supplemented with different doses of SkQ1 for two or three weeks. Control groups of rats were fed the same diet supplemented with NaBr. Anaesthetized rats were subjected to 40-min regional myocardial ischemia and 1-h reperfusion. Myocardial infarct size was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining method. SkQ1-fed rats (125 nmol/kg/day for two weeks and 250 nmol/kg/day for two and three weeks) revealed significantly smaller myocardial infarction and less lactate dehydrogenase (LDH) and creatine kinase-MB fraction (CK-MB) activity elevations in plasma at the end of reperfusion compared with the controls. This effect was combined with improvement of energy state of the area at risk at the end of reperfusion, namely, augmentation of adenine nucleotide content, two-fold increase in phosphocreatine, reduction of lactate accumulation and decrease of lactate/pyruvate ratio in myocardial tissue. Therefore, nutritional supplementation with SkQ1 renders the hearts resistant to ischemia-reperfusion injury affecting oxidative metabolism of postischemic cardiomyocytes. PMID:20001981

Pisarenko, O I; Serebriakova, L I; Tskitishvili, O V; Studneva, I M

2009-01-01

149

Reduced hemodynamic load aids low-dose resveratrol in reversing cardiovascular defects in hypertensive rats.  

PubMed

Cardiac hypertrophy and associated myocardial remodeling is one of the main complications of hypertension resulting in the development of heart failure. It is of great significance to explore novel treatments to reverse cardiac hypertrophy in hypertensives with or without affecting blood pressure. In the present study, we investigated whether low-dose resveratrol alone or in a combination with a blood pressure-lowering agent can reverse hypertension-induced cardiovascular dysfunction. Twenty-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were treated with resveratrol (2.5 mg?kg?¹ per day) and/or hydralazine (25 mg?kg?¹ per day) for 8 weeks. Blood pressure, cardiac structure and function, and electrocardiogram measurements were examined. Pressure myography of resistance arteries, histological examinations of heart tissues, oxidative stress and inflammatory measurements were also preformed to assess the efficacy of the treatment. Although resveratrol treatment alone was ineffective in reducing systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling, it significantly prevented the systolic impairment and reduced myocardial fibrosis, and reduced oxidative stress and inflammation in hypertensive rats. Furthermore, a combination of resveratrol with hydralazine treatment significantly reduced blood pressure, improved systolic and diastolic function, decreased fibrosis and improved vascular geometry. In summary, low-dose resveratrol itself was unable to reduce systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling. However, resveratrol alone alleviated cardiac fibrosis and some of the functional abnormalities in SHRs. And a combination of resveratrol with hydralazine was more effective than resveratrol or hydralazine alone in improving overall cardiovascular parameters. PMID:23784505

Thandapilly, Sijo Joseph; Louis, Xavier Lieben; Behbahani, John; Movahed, Ali; Yu, Liping; Fandrich, Robert; Zhang, Shetuan; Kardami, Elissavet; Anderson, Hope D; Netticadan, Thomas

2013-10-01

150

Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats  

PubMed Central

Background and purpose Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head. Methods We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining. Results The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads. Interpretation Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.

2012-01-01

151

Propolis reduces oxidative stress in l-NAME-induced hypertension rats.  

PubMed

The inhibition in the synthesis or bioavailability of nitric oxide (NO) has an important role in progress of hypertension. The blocking of nitric oxide synthase activity may cause vasoconstriction with the formation of reactive oxygen species (ROS). Propolis is a resinous substance collected by honey bees from various plants. Propolis has biological and pharmacological properties. The aim of this study was to examine the effect of propolis on catalase (CAT) activity, malondialdehyde (MDA) and NO levels in the testis tissues of hypertensive rats by N?-nitro-l-arginine methyl ester (l-NAME). Rats have received nitric oxide synthase inhibitor (l-NAME, 40 mg kg(-1) , intraperitoneally) for 15 days to produce hypertension and propolis (200 mg kg(-1) , by gavage) during the last 5 days. MDA level in l-NAME-treated group significantly increased compared with control group (P < 0.01). MDA level of l-NAME + propolis-treated rats significantly reduced (P < 0.01) compared with l-NAME-treated group. CAT activity and NO level significantly reduced (P < 0.01) in l-NAME group compared with control group. There were no statistically significant increases in the CAT activity and NO level of the l-NAME + propolis group compared with the l-NAME-treated group (P > 0.01). These results suggest that propolis changes CAT activity, NO and MDA levels in testis of l-NAME-treated animals, and so it may modulate the antioxidant system. PMID:23788129

Selamoglu Talas, Zeliha

2014-03-01

152

Cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in conscious rats  

PubMed Central

The response to myocardial ischemia is complex and involves the cardio-cardiac sympathetic reflex. Specifically, cardiac spinal (sympathetic) afferents are excited by ischemic metabolites and elicit an excitatory sympathetic reflex, which plays a major role in the genesis of ventricular arrhythmias. For example, brief myocardial ischemia leads to ATP release, which activates cardiac spinal afferents through stimulation of P2 receptors. Clinical work with patients and preclinical work with animals document that disruption of this reflex protects against ischemia-induced ventricular arrhythmias. However, the role of afferent signals in the initiation of sustained ventricular tachycardia has not been investigated. Therefore, we tested the hypothesis that cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in adult (12–15 wk of age), conscious, male Sprague-Dawley rats. To test this hypothesis, the susceptibility to ventricular tachyarrhythmias produced by occlusion of the left main coronary artery was determined in two groups of conscious rats: 1) deafferentation (bilateral excision of the T1-T5 dorsal root ganglia) and 2) control (sham deafferentation). The ventricular arrhythmia threshold (VAT) was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Results document a significantly higher VAT in the deafferentation group (7.0 ± 0.7 min) relative to control (4.3 ± 0.3 min) rats. The decreased susceptibility to tachyarrhythmias with deafferentation was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST segment elevation) during ischemia.

Lujan, Heidi L.; Krishnan, Sandhya

2011-01-01

153

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

PubMed

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

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

2014-03-15

154

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats  

PubMed Central

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.

Odena, Gemma; Miquel, Mireia; Serafin, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartoli, Ramon

2012-01-01

155

Gestational or acute restraint in adulthood reduces levels of 5?-reduced testosterone metabolites in the hippocampus and produces behavioral inhibition of adult male rats  

PubMed Central

Stressors, during early life or adulthood, can alter steroid-sensitive behaviors, such as exploration, anxiety, and/or cognitive processes. We investigated if exposure to acute stressors in adulthood may alter behavioral and neuroendocrine responses of male rats that were exposed to gestational stress or not. We hypothesized that rats exposed to gestational and acute stress may show behavioral inhibition, increased corticosterone, and altered androgen levels in the hippocampus. Subjects were adult, male offspring of rat dams that were restrained daily on gestational days 14–20, or did not experience this manipulation. Immediately before testing, rats were restraint stressed for 20 min or not. During week 1, rats were tested in a battery of tasks, including the open field, elevated plus maze, social interaction, tailflick, pawlick, and defensive burying tasks. During week 2, rats were trained and tested 24 h later in the inhibitory avoidance task. Plasma corticosterone and androgen levels, and hippocampal androgen levels, were measured in all subjects. Gestational and acute restraint stress increased plasma levels of corticosterone, and reduced levels of testosterone's 5?-reduced metabolites, dihydrotestosterone (DHT) and 3?-androstanediol (3?-diol), but not the aromatized metabolite, estradiol (E2), in plasma or the hippocampus. Gestational and acute restraint stress reduced central entries made in the open field, and latencies to enter the shock-associated side of the inhibitory avoidance chamber during testing. Gestational stress reduced time spent interacting with a conspecific. These data suggest that gestational and acute restraint stress can have actions to produce behavioral inhibition coincident with increased corticosterone and decreased 5?-reduced androgens of adult male rats. Thus, gestational stress altered neural circuits involved in the neuroendocrine response to acute stress in early adulthood.

Walf, Alicia A.; Frye, Cheryl A.

2012-01-01

156

Impaired dilation of skeletal muscle microvessels to reduced oxygen tension in diabetic obese Zucker rats.  

PubMed

This study determined alterations to hypoxic dilation of isolated skeletal muscle resistance arteries (gracilis arteries; viewed via television microscopy) from obese Zucker rats (OZR) compared with lean Zucker rats (LZR). Hypoxic dilation was reduced in OZR compared with LZR. Endothelium removal and cyclooxygenase inhibition (indomethacin) severely reduced this response in both groups, although nitric oxide synthase inhibition (N(omega)-nitro-L-arginine methyl ester) reduced dilation in LZR only. Treatment of vessels with a PGH(2)-thromboxane A(2) receptor antagonist had no effect on hypoxic dilation in either group. Arterial dilation to arachidonic acid, iloprost, acetylcholine, and sodium nitroprusside was reduced in OZR versus LZR, although dilation to forskolin and aprikalim was unaltered. Treatment of arteries from OZR with oxidative radical scavengers increased dilation to hypoxia and agonists, with no effect on responses in LZR. The restored hypoxic dilation in OZR was abolished by indomethacin. These results suggest that hypoxic dilation of skeletal muscle microvessels from LZR represents the summated effects of prostanoid and nitric oxide release, whereas the impaired response of vessels in OZR may reflect scavenging of PGI(2) by superoxide anion. PMID:11557545

Frisbee, J C

2001-10-01

157

Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide  

PubMed Central

Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24?h after the insult. However, both differences disappeared between 24 and 72?h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria.

2012-01-01

158

Viral bronchiolitis in young rats causes small airway lesions that correlate with reduced lung function.  

PubMed

Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity. PMID:23763491

Sorkness, Ronald L; Szakaly, Renee J; Rosenthal, Louis A; Sullivan, Ruth; Gern, James E; Lemanske, Robert F; Sun, Xin

2013-11-01

159

Rosiglitazone Reduces Blood Pressure in Female Dahl Salt-sensitive Rats  

PubMed Central

Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome proliferator activated receptor-gamma (PPAR?) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPAR? agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NOx; index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NOx in both groups. High salt diet increased NOx in all groups but ROSI only increased NOx in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPAR-gamma activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.

Sartori-Valinotti, Julio C.; Venegas-Pont, Marcia R.; LaMarca, Babbette B.; Romero, Damian G.; Yanes, Licy L.; Racusen, Lorraine C.; Jones, Allison V.; Ryan, Michael J.; Reckelhoff, Jane F.

2009-01-01

160

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

PubMed

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

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

2014-03-15

161

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

PubMed Central

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 ratsor 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.

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

2013-01-01

162

Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.  

PubMed

Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders. PMID:21712072

Sigwalt, A R; Budde, H; Helmich, I; Glaser, V; Ghisoni, K; Lanza, S; Cadore, E L; Lhullier, F L R; de Bem, A F; Hohl, A; de Matos, F J; de Oliveira, P A; Prediger, R D; Guglielmo, L G A; Latini, A

2011-09-29

163

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction  

PubMed Central

Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in e Marchigian Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced gray matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn gray matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction.

Gozzi, Alessandro; Agosta, Federica; Massi, Maurizio; Ciccocioppo, Roberto; Bifone, Angelo

2014-01-01

164

How forelimb and hindlimb function changes with incline and perch diameter in the green anole, Anolis carolinensis.  

PubMed

The range of inclines and perch diameters in arboreal habitats poses a number of functional challenges for locomotion. To effectively overcome these challenges, arboreal lizards execute complex locomotor behaviors involving both the forelimbs and the hindlimbs. However, few studies have examined the role of forelimbs in lizard locomotion. To characterize how the forelimbs and hindlimbs differentially respond to changes in substrate diameter and incline, we obtained three-dimensional high-speed video of green anoles (Anolis carolinensis) running on flat (9 cm wide) and narrow (1.3 cm) perches inclined at 0, 45 and 90 deg. Changes in perch diameter had a greater effect on kinematics than changes in incline, and proximal limb variables were primarily responsible for these kinematic changes. In addition, a number of joint angles exhibited greater excursions on the 45 deg incline compared with the other inclines. Anolis carolinensis adopted strategies to maintain stability similar to those of other arboreal vertebrates, increasing limb flexion, stride frequency and duty factor. However, the humerus and femur exhibited several opposite kinematic trends with changes in perch diameter. Further, the humerus exhibited a greater range of motion than the femur. A combination of anatomy and behavior resulted in differential kinematics between the forelimb and the hindlimb, and also a potential shift in the propulsive mechanism with changes in external demand. This suggests that a better understanding of single limb function comes from an assessment of both forelimbs and hindlimbs. Characterizing forelimb and hindlimb movements may reveal interesting functional differences between Anolis ecomorphs. Investigations into the physiological mechanisms underlying the functional differences between the forelimb and the hindlimb are needed to fully understand how arboreal animals move in complex habitats. PMID:22675190

Foster, Kathleen L; Higham, Timothy E

2012-07-01

165

Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.  

PubMed

The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity. PMID:22878390

Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

2012-01-01

166

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat  

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

167

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

SciTech Connect

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.

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

1988-08-01

168

Trigeminal integration of vestibular and forelimb nerve inputs.  

PubMed

Experiments were carried out on anaesthetized guinea pigs to evaluate whether vestibular and somatosensory informations converge upon the same trigeminal motoneurones and, if so, how they interact in the modulation of their activity. It was found that excitatory responses occurred in these motoneurones when an appropriate electrical stimulation was applied to the common radial nerve. The same was true if the electrical stimulus was applied to the vestibular ampullae. In another set of experiments the stimulation was applied both to the vestibular ampullae and to the common radial nerve at various time-intervals. The amplitude of the motoneuronal responses to common radial nerve stimulation was reduced when preceded by a vestibular stimulation. The same was true when the sequence of stimulations was reversed: in this case there was a decrease in amplitude of the testing response to vestibular stimulation. The degree of these reductions depended upon the time-interval elapsed between the afferent stimulations. The maximal degree of depression was observed at 4-6 ms time-interval for conditioning vestibular stimulation and at 10-12 ms time-interval for conditioning radial nerve stimulation. It appears, therefore, that somatosensory and vestibular signals may modulate the activity of trigeminal motor units innervating masticatory muscles, suggesting that extratrigeminal afferents may control the contraction of these muscles. PMID:9934434

Deriu, F; Podda, M V; Chessa, G; Tolu, E

1999-02-01

169

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

PubMed Central

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.

Bhattacharya, Koushik; Mukherjee, Soumya

2014-01-01

170

The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats.  

PubMed

The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI) rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05). Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats. PMID:24918539

Kim, Jae Goo; Lim, Dong Wook; Cho, Suengmok; Han, Daeseok; Kim, Yun Tai

2014-01-01

171

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum.  

PubMed

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague-Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis(®) homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study. PMID:21698419

Alirezaei, Masoud; Jelodar, Gholamali; Niknam, Parvin; Ghayemi, Zeynab; Nazifi, Saeed

2011-12-01

172

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

PubMed

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

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

2012-09-15

173

A1 Noradrenergic Neurons Lesions Reduce Natriuresis and Hypertensive Responses to Hypernatremia in Rats  

PubMed Central

Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280–340 g) received nanoinjections of antidopamine-?-hydroxylase-saporin (A1 lesion, 0.105 ng.nL?1) or free saporin (sham, 0.021 ng.nL?1) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg?1, b.wt., for longer than 1 min). In the sham-group (n?=?8), HS induced a sustained pressor response (?MAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-D?H-saporin-treated rats (n?=?11)were significantly smaller(?MAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-D?H-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

da Silva, Elaine Fernanda; Freiria-Oliveira, Andre Henrique; Custodio, Carlos Henrique Xavier; Ghedini, Paulo Cesar; Bataus, Luiz Artur Mendes; Colombari, Eduardo; de Castro, Carlos Henrique; Colugnati, Diego Basile; Rosa, Daniel Alves; Cravo, Sergio L. D.; Pedrino, Gustavo Rodrigues

2013-01-01

174

A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.  

PubMed

Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-?-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1)) or free saporin (sham, 0.021 ng.nL(-1)) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1), b.wt., for longer than 1 min). In the sham-group (n?=?8), HS induced a sustained pressor response (?MAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-D?H-saporin-treated rats (n?=?11)were significantly smaller(?MAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-D?H-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid. PMID:24039883

da Silva, Elaine Fernanda; Freiria-Oliveira, André Henrique; Custódio, Carlos Henrique Xavier; Ghedini, Paulo César; Bataus, Luiz Artur Mendes; Colombari, Eduardo; de Castro, Carlos Henrique; Colugnati, Diego Basile; Rosa, Daniel Alves; Cravo, Sergio L D; Pedrino, Gustavo Rodrigues

2013-01-01

175

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

PubMed Central

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.

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

176

The CCKB antagonist CI988 reduces food intake in fasted rats via a dopamine mediated pathway.  

PubMed

Studies have shown a reduction of food intake following peripheral and brain injection of CCK. However, it remains to be established whether endogenous central CCK is involved in the regulation of food intake. We investigated the role of central CCK in the regulation of food intake by pharmacological manipulation of the CCK(B) (CCK(2)) receptor system. Intracerebroventricularly (ICV) cannulated male Sprague Dawley rats were fasted for 24h and received an ICV injection of the CCK(B) receptor antagonist CI988 at a dose of 10 nmol or 49 nmol or vehicle. Another group received two consecutive ICV injections consisting of the corticotropin-releasing factor (CRF) receptor-1 (CRF(1)) antagonist, CP376395 (3 nmol) or the CRF(2) receptor antagonist, K41498 (2 nmol) alone, or followed by CI988 (49 nmol). Lastly, another group of rats received an intraperitoneal (IP) injection of the dopamine antagonist, flupentixol (~197 and ~493nmol/kg) alone, or followed by CI988 (49 nmol, ICV). Cumulative food intake was assessed for 11h. Vehicle injected rats showed a robust feeding response. CI988 at 49 nmol reduced food intake by 30% starting at 2h post injection. CP376395 and K41498 had no effect on food intake. Flupentixol injected IP at a dose of 197 and 493 nmol/kg alone did not modulate food intake whereas the higher dose blocked the CI988-induced reduction of feeding. During the dark phase, CI988 had no effect on food intake in unfasted rats. In summary, CCK(B) signaling is involved in the regulation of food intake after a fast likely by downstream dopamine signaling. PMID:23200724

Frommelt, Lisa; Lembke, Vanessa; Hofmann, Tobias; Goebel-Stengel, Miriam; Mönnikes, Hubert; Wiedenmann, Bertram; Klapp, Burghard F; Stengel, Andreas; Kobelt, Peter

2013-01-01

177

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal alpha-adrenoceptors  

PubMed Central

In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists to known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 minutes under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2 hours, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2 mg/kg, i.p. or 30 ?g, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1 mg/kg, i.p.) and failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine (10 ?g), an ?2-adrenergic antagonist, reduced the EA-induced analgesia in a dose-dependent manner, whereas terazosin (10 ?g), an ?1-adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal ?2-adrenoceptor mechanisms.

Koo, Sung Tae; Lim, Kyu Sang; Chung, Kyungsoon; Ju, Hyunsu; Chung, Jin Mo

2008-01-01

178

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

PubMed Central

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.

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

2014-01-01

179

Histological study of the innervation of the suspensory ligament of the forelimb of the horse.  

PubMed

The innervation pattern of the interosseus muscle of the forelimb was studied in two ponies and two horses. The nerves of the suspensory ligament were studied histologically after neurectomy of the ulnar and median nerve branches proximal to the carpal joint. The results demonstrated that the interosseus muscle is innervated by the deep branch of the lateral palmar nerve which emerges at the level of the midcarpal region and contains fibres from the ulnar and the median nerve. These findings provide evidence that an ulnar nerve block proximal to the accessory bone would fail to anaesthetise the entire suspensory ligament. PMID:9682420

Muylle, S; Desmet, P; Simoens, P; Lauwers, H; Vlaminck, L

1998-05-30

180

Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet response to thrombin stimulation.  

PubMed

Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidemia. The aim of our study was to characterize some properties of platelets and/or erythrocytes (cytosolic calcium handling, intracellular pH regulation and thrombin responsiveness) in a new model of genetic hypertension associated with hyperlipidemia-Prague hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal intracellular pHi values and similar buffering capacity as control rats but their pHi response to thrombin stimulation was substantially reduced. It can be concluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyceridemic rats. PMID:8761314

Zicha, J; Kunes, J; David-Dufilho, M; Pernollet, M G; Devynck, M A

1996-01-01

181

Inhibition of carrier-mediated uptake of epirubicin reduces cytotoxicity in primary culture of rat hepatocytes.  

PubMed

Epirubicin, an antineoplastic drug, is considered to be taken up by tumor cells via a common carrier by facilitated diffusion and is then pumped out in an energy-dependent manner because epirubicin is a substrate for P-glycoprotein (P-gp). However, this study investigated the details of the influx mechanism of epirubicin and demonstrated that epirubicin uptake was mediated by active carrier systems in addition to facilitated diffusion in the primary culture of rat hepatocytes. The uptake of epirubicin gradually increased in a saturated manner when the concentrations were between 1 x 10(-7) M and 1 x 10(-6) M. In contrast, the uptake increased progressively in a linear manner when the concentration was high (greater than 1 x 10(-6) M). The uptake of epirubicin at a clinical concentration (7.5 x 10(-7) M) was significantly reduced at 4 degrees C and significantly inhibited when pretreated with metabolic inhibitors (carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), rotenone and sodium azide) by nearly 25%. Furthermore, an organic anion transporter inhibitor, namely, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS); organic anion transport substrates, namely, para-aminohippurate (PAH), taurocholic acid and estradiol 17-beta-D-glucuronide; and organic cation transporter inhibitors, namely, verapamil and tetraethylammonium significantly reduced the uptake of epirubicin. Furthermore, pretreatment with verapamil and PAH significantly prevented epirubicin-induced reduction of proliferative activity in rat hepatocytes. These results indicated that the uptake of epirubicin was induced, at least in part, by the active transport protein in rat hepatocytes; the inhibition of the probable transport protein protected the intact normal cells from the injury induced by the cytotoxicity of epirubicin. PMID:17604344

Iwakiri, Tomomi; Okumura, Manabu; Hidaka, Muneaki; Kumagai, Yuki; Ichihara, Emi; Kawano, Yohei; Arimori, Kazuhiko

2008-04-01

182

Irradiation of rat brain reduces P-glycoprotein expression and function  

PubMed Central

The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats were irradiated with single doses of 2–25?Gy followed by 10?mg?kg?1 of the P-gp substrate cyclosporine A (CsA) intravenously (i.v.), with once 15?Gy followed by CsA (10, 15 or 20?mg?kg?1), or with fractionated irradiation (4 × 5?Gy) followed by CsA (10?mg?kg?1) 5 days later. Additionally, four groups of three rats received 25?Gy once and were killed 10, 15, 20 or 25 days later. The brains were removed and P-gp detected immunohistochemically. P-gp function was assessed by [11C]carvedilol uptake using quantitative autoradiography. Irradiation increased [11C]carvedilol uptake dose-dependently, to a maximum of 20% above non irradiated hemisphere. CsA increased [11C]carvedilol uptake dose-dependently in both hemispheres, but more (P<0.001) in the irradiated hemisphere. Fractionated irradiation resulted in a lost P-gp expression 10 days after start irradiation, which coincided with increased [11C]carvedilol uptake. P-gp expression decreased between day 15 and 20 after single dose irradiation, and increased again thereafter. Rat brain irradiation results in a temporary decreased P-gp function.

Bart, J; Nagengast, W B; Coppes, R P; Wegman, T D; van der Graaf, W T A; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N H

2007-01-01

183

Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress.  

PubMed

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17?-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner. PMID:20579403

Huang, Yan-Hong; Zhang, Qing-Hong

2010-11-01

184

Amlodipine Reduces Inflammation despite Promoting Albuminuria in the Streptozotocin-Induced Diabetic Rat.  

PubMed

Amlodipine reduces blood pressure; however, its effect in the diabetic kidney irrespective of its blood pressure-lowering effects is unclear. This study examined the effects of amlodipine (0, 5, 10 and 20 mg/kg; D(A0), D(A5), D(A10) and D(A20), respectively) for 12 weeks on renal functional and structural changes in the streptozotocin-induced diabetic rat, a nonhypertensive model of diabetes-associated hyperfiltration. Compared with nondiabetic rats, diabetes (D) was associated with increased urine albumin excretion (UAE, 12.6 ± 3.40 vs. 3.73 ± 1.14 mg/day), glomerular filtration rate (2.17 ± 0.09 vs. 1.64 ± 0.12 ml/min/g kidney weight), glomerulosclerosis (0.21 ± 0.03 vs. 0.05 ± 0.01 AU) and infiltration of inflammatory cells (18.5 ± 2.78 vs. 6.92 ± 0.70 cells/cm(2)), but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg). While D(A20) abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight) and inflammatory cell abundance (6.0 ± 0.79 cells/cm(2)), it exacerbated UAE (43.5 ± 8.49 mg/day) and increased MAP (132 ± 3.76 mm Hg), but had no effect on renal pathology. These data suggest that amlodipine reduces renal inflammation and abolished glomerular hyperfiltration, but increases blood pressure and exacerbates albuminuria in the rat model of normotensive diabetic kidney disease. We conclude that amlodipine may have limited renoprotective effects in the face of hyperfiltration and absence of elevated blood pressure. PMID:22811694

Flynn, Elizabeth R; Marbury, David C; Sawyer, R Taylor; Lee, Jonathan; Teutsch, Christine; Kauser, Katalin; Maric-Bilkan, Christine

2012-01-01

185

Reduced effect of taxol on plasma protein secretion by developing rat liver.  

PubMed

The effect of taxol, a potent stabilizer of microtubules, on plasma protein secretion by slices prepared from mature and developing rat liver was determined. After 4 hr of incubation, taxol (50 microM) inhibited albumin secretion by only 10% on gestation Day 19, by 16% 4 days after birth, but by 40% in the adult. Inhibition of glycoprotein secretion by taxol was similar to that of albumin secretion at all ages studied. Combined with information obtained from previous investigations, the present study indicates that agents that either inhibit microtubular assembly or that stabilize microtubules both have a reduced capacity to inhibit hepatic protein secretion during development. These findings suggest that a reduced requirement for microtubular participation in protein secretion is present in developing liver. PMID:2868546

Kaufman, S S; Tuma, D J; Vanderhoof, J A

1986-02-01

186

Dizocilpine reduces head diameter of dendritic spines in the hippocampus of adolescent rats.  

PubMed

Cognitive deficits are the core symptoms of schizophrenia. Spine deficits have been found in hippocampus of schizophrenia patients, and were associated with cognitive impairments. N-methyl-D-asparate receptors (NMDARs) had been known to play a critical role in synaptic pruning and stabilization during adolescence. In the present study, male adolescent rats were exposed to dizocilpine (MK-801) (0.2mg/kg i.p qd) or 0.9% saline for 14 days. Then spatial memory, spine morphological changes and RhoA, Rac1, Cdc42 mRNA levels in hippocampus were measured. As a result, MK-801 impaired spatial memory in the adolescent rats, as well as reduced the proportion of mushroom spines and increased the proportion of stubby spines in hippocampus. MK-801 also reduced the expression levels of Rac1 and Cdc42 mRNA and upregulated RhoA mRNA in hippocampus. These results imply that subchronic MK-801 administration during adolescence might disturb the expression of RhoA, Rac1 and Cdc42 mRNA, and then lead to the decay of the spines in hippocampus, which could be involved in cognitive impairments in schizophrenia. PMID:23747234

Han, Dai; Xu, Li; Xiao, Honglei; Prado Schmidt, Georgia C; Shi, Shenxun

2013-11-30

187

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

PubMed Central

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

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

2011-01-01

188

A model of preeclampsia in rats: the reduced uterine perfusion pressure (RUPP) model  

PubMed Central

Preeclampsia is defined as new-onset hypertension with proteinuria after 20 wk gestation and is hypothesized to be due to shallow trophoblast invasion in the spiral arteries thus resulting in progressive placental ischemia as the fetus grows. Many animal models have been developed that mimic changes in maternal circulation or immune function associated with preeclampsia. The model of reduced uterine perfusion pressure in pregnant rats closely mimics the hypertension, immune system abnormalities, systemic and renal vasoconstriction, and oxidative stress in the mother, and intrauterine growth restriction found in the offspring. The model has been successfully used in many species; however, rat and primate are the most consistent in comparison of characteristics with human preeclampsia. The model suffers, however, from lack of the ability to study the mechanisms responsible for abnormal placentation that ultimately leads to placental ischemia. Despite this limitation, the model is excellent for studying the consequences of reduced uterine blood flow as it mimics many of the salient features of preeclampsia during the last weeks of gestation in humans. This review discusses these features.

Li, Jing; LaMarca, Babbette

2012-01-01

189

Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism  

SciTech Connect

Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl/sub 2/, a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively.

Wilkes, B.M.

1987-04-01

190

Reduced effect of stimulation of AMPA receptors on cerebral O? consumption in a rat model of autism.  

PubMed

Previous work demonstrated that basal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activity did not contribute to the elevated regional cerebral O? consumption in the brains of Eker rat (an autism-tuberous sclerosis model). We tested the hypothesis that increased stimulation of AMPA receptors also would not augment cerebral O? consumption in the Eker rat. Three cortical sites were prepared for administration of saline, 10?? and 10?³ M AMPA in young (4 weeks) male control Long Evans and Eker rats (70-100 g). Cerebral blood flow (¹?C-iodoantipyrine) and O? consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. Receptor levels were studied through Western analysis of the GLuR1 subunit of the AMPA receptor. We found significantly increased cortical O? consumption (+33%) after 10?? M AMPA in control rats. The higher dose of AMPA did not further increase consumption. In the Eker rats, neither dose led to a significant increase in cortical O? consumption. Regional blood flow followed a similar pattern to oxygen consumption but cortical O? extraction did not differ. Cortical AMPA receptor protein levels were significantly reduced (-21%) in the Eker compared to control rats. Both O? consumption and blood flow were significantly elevated in the pons of the Eker rats compared to control. These data demonstrate a reduced importance of AMPA receptors in the control of cortical metabolism, related to reduced AMPA receptor protein, in the Eker rat. This suggests that increasing AMPA receptor activity may not be an effective treatment for children with autism spectrum disorders as they also have reduced AMPA receptor number. PMID:22722031

Weiss, Harvey R; Liu, Xia; Grewal, Parneet; Chi, Oak Z

2012-10-01

191

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis  

PubMed Central

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

192

Reduced dopamine synthesis and protein levels in the median eminence of blinded anosmic female rats: relation to the pineal.  

PubMed

Twenty 25 day old female Sprague-Dawley rats were enucleated (BL) and olfactory bulbectomized (ANOS) and one half of these were also pinealectomized (PINX). Ten female rats received no surgical manipulation (CONTROL). Thirty days later each rat received NSD-1015 30 minutes before killing. The median eminence, telencephalon and hypothalamus were collected. Tyrosine hydroxylase activity, determined by the accumulation of DOPA after NSD-1015, was significantly reduced in the median eminence of BL+ANOS (p less than 0.05). Dopamine and noradrenaline levels in this tissue were not different among the experimental groups. Protein levels in the median eminence was also significantly reduced in BL+ANOS and PINX rats. None of the above parameters were different in the hypothalamus among the 3 experimental groups. These data suggest that the activity of the dopaminergic tuberoinfundibular neurons is reduced in both BL+ANOS and PINX rats. The reduced protein may reflect a reduction in protein synthesis, a decrease in numbers of nerve terminals or a reduction of pituitary regulatory hormones in BL+ANOS and PINX rats. PMID:6125950

Morgan, W W; Reiter, R J

1982-01-01

193

Reduced antioxidative capacity in liver mitochondria from bile duct ligated rats  

Microsoft Academic Search

Lipid peroxidation and antioxidative mechanisms were investigated in liver mitochondria from bile duct ligated rats (BDL rats) and correlated with the activity of enzyme complexes of the electron transport chain. In comparison to pair-fed control rats, BDL rats had increased concentrations of thiobarbituric acid reacting substances (TBARS) per gram of liver and per milligram of mitochondrial protein 3, 7, 14,

Stephan Krähenbühl; Christine Talos; Bernhard H. Lauterburg; Jürg Reichen

1995-01-01

194

Functional anatomy of the gibbon forelimb: adaptations to a brachiating lifestyle  

PubMed Central

It has been shown that gibbons are able to brachiate with very low mechanical costs. The conversion of muscle activity into smooth, purposeful movement of the limb depends on the morphometry of muscles and their mechanical action on the skeleton. Despite the gibbon's reputation for excellence in brachiation, little information is available regarding either its gross musculoskeletal anatomy or its more detailed muscle–tendon architecture. We provide quantitative anatomical data on the muscle–tendon architecture (muscle mass, physiological cross-sectional area, fascicle length and tendon length) of the forelimb of four gibbon species, collected by detailed dissections of unfixed cadavers. Data are compared between different gibbon species and with similar published data of non-brachiating primates such as macaques, chimpanzees and humans. No quantitative differences are found between the studied gibbon species. Both their forelimb anatomy and muscle dimensions are comparable when normalized to the same body mass. Gibbons have shoulder flexors, extensors, rotator muscles and elbow flexors with a high power or work-generating capacity and their wrist flexors have a high force-generating capacity. Compared with other primates, the elbow flexors of gibbons are particularly powerful, suggesting that these muscles are particularly important for a brachiating lifestyle. Based on this anatomical study, the shoulder flexors, extensors, rotator muscles, elbow flexors and wrist flexors are expected to contribute the most to brachiation.

Michilsens, Fana; Vereecke, Evie E; D'Aout, Kristiaan; Aerts, Peter

2009-01-01

195

The prevalence and risk factors associated with forelimb skin abrasions and sole bruising in preweaning piglets.  

PubMed

The presence of skin abrasions and sole bruising in 264 preweaning piglets (1-30 days old) from 13 breeding units in south west England was investigated in 1995. The mean prevalence of forelimb skin abrasions among the pigs on the study farms was 36% (range 0-59%) and sole bruising was 50% (range 0-95%). Skin abrasions were located on three aspects on the front limbs: the carpus, the metacarpus and the digit. Lesions occurred early in a piglet's life; the modal ages for sole bruising was 4 days and for skin abrasions were 5 and 10 days. The presence of skin abrasions on the front limbs was significantly associated with the presence of sole bruising on the front feet. Logistic regression indicated that part-concrete, part-round-mesh (OR 56.4) and part-concrete, part-metal-rods floors (OR 15.9) and exposed aggregate (OR 4.6) were associated with an increased odds of sole bruising while the presence of sparse straw (OR 0.12) or deep straw (OR 0.12) in the pen was associated with lower odds of sole bruising. The same floor type (part-concrete, part-round-mesh) was associated with increased odds of forelimb skin abrasions (OR 2.2). A worn floor surface where the solid adjoined the perforated area (OR 4.6) and the presence of sparse shavings (OR 1.7) were also associated with an increased risk of skin abrasions. PMID:10327440

Mouttotou, N; Hatchell, F M; Green, L E

1999-04-27

196

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

PubMed Central

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.

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

2014-01-01

197

Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats.  

PubMed

We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treatment with STZ or the vehicle. The fundus images were captured with the digital fundus camera system for small animals we developed and diameters of retinal blood vessels contained in the digital images were measured. Epinephrine increased the diameters of retinal blood vessels, but the vasodilator responses were reduced in diabetic rats. Dopamine produced a biphasic retinal vascular response with an initial vasoconstriction followed by a vasodilation. The vasoconstrictor effects of dopamine on retinal arterioles were enhanced in diabetic rats, whereas the difference between the two groups was abolished by treatment with propranolol. The vasodilator effect of isoproterenol, but not of the activator of adenylyl cyclase colforsin, on retinal blood vessels was reduced in diabetic rats. No difference in vasoconstriction of retinal blood vessels to phenylephrine between non-diabetic and diabetic rats was observed. The vasodilator responses of retinal blood vessels to 1,1-dimethyl-4-phenylpiperazinium, a ganglionic nicotinic receptor agonist, were also attenuated in diabetic rats. These results suggest that diabetes mellitus alters the retinal vascular responses to circulating catecholamines and the impairment of vasodilator responses mediated by beta-adrenoceptors contributes to the alteration. PMID:18585480

Nakazawa, Taisuke; Sato, Ayumi; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

2008-01-01

198

Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats  

PubMed Central

Painful stimuli during neonatal stage may affect brain development and contribute to abnormal behaviors in adulthood. Very few specific therapies are available for this developmental disorder. A better understanding of the mechanisms and consequences of painful stimuli during the neonatal period is essential for the development of effective therapies. In this study, we examined brain reactions in a neonatal rat model of peripheral inflammatory pain. We focused on the inflammatory insult-induced brain responses and delayed changes in behavior and pain sensation. Postnatal day 3 pups received formalin injections into the paws once a day for 3 days. The insult induced dysregulation of several inflammatory factors in the brain and caused selective neuronal cell death in the cortex, hippocampus and hypothalamus. On postnatal day 21, rats that received the inflammatory nociceptive insult exhibited increased local cerebral blood flow in the somatosensory cortex, hyperalgesia, and decreased exploratory behaviors. Based on these observations, we tested recombinant human erythropoietin (rhEPO) as a potential treatment to prevent the inflammatory pain-induced changes. rhEPO treatment (5,000 U/kg/day, i.p.), coupled to formalin injections, ameliorated neuronal cell death and normalized the inflammatory response. Rats that received formalin plus rhEPO exhibited normal levels of cerebral blood flow, pain sensitivity and exploratory behavior. Treatment with rhEPO also restored normal brain and body weights that were reduced in the formalin group. These data suggest that severe inflammatory pain has adverse effects on brain development and rhEPO may be a possible therapy for the prevention and treatment of this developmental disorder.

2011-01-01

199

Topiramate reduces non-convulsive seizures after focal brain ischemia in the rat.  

PubMed

Acute "silent" seizures after brain injury are associated with a worsening of patient outcome and are often refractory to anti-epileptic drug (AED) therapy. In the present study we evaluated topiramate (TPM, 1-30 mg/kg, i.v.) in a rodent model of spontaneous non-convulsive seizure (NCS) activity induced by focal cerebral ischemia. For seizure detection, electroencephalographic (EEG) activity was continuously recorded for 24h in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAo). Infarct volume, neurological deficit, and NCS were evaluated by an experimenter blinded to the treatment group. All vehicle treated rats (7/7) exhibited NCS following MCAo. TPM treatment, delivered at 20 min post-occlusion and prior to onset of NCS activity, dose-dependently reduced the incidence of NCS (ED(50)=21.1mg/kg). The highest dose of TPM tested (30 mg/kg) exhibited maximal reductions of 76% in the number of NCS/rat (vehicle=22.1+/-5.3, TPM=4.4+/-3.2, P<0.05), 80% in the total time of NCS (vehicle=1259+/-337 s, TPM=253+/-220 s, P<0.05), 20% in core brain infarction (vehicle=45+/-1%, TPM=36+/-4%, percent of ipsilateral volume corrected for swelling, P<0.05), and 38% in neurological deficit score (vehicle=7.4+/-1.2, TPM=4.6+/-1.5, P<0.05). Despite efficacy as a pre-seizure treatment, TPM was not effective when delivered immediately following onset of the first NCS event (36+/-5 min post-MCAo). In conclusion, TPM exhibited significant efficacy for the prophylactic treatment of brain-injury induced NCS and represents a novel class of AED for treatment of this type of silent brain seizure. PMID:18063309

Williams, Anthony J; Tortella, Frank C; Gryder, Divina; Hartings, Jed A

2008-01-01

200

Preconditioning somatothermal stimulation on Qimen (LR14) reduces hepatic ischemia/reperfusion injury in rats  

PubMed Central

Background In human beings or animals, ischemia/reperfusion (I/R) injury of the liver may occur in many clinical conditions, such as circulating shock, liver transplantation and surgery and several other pathological conditions. I/R injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators. This study aimed at studying the effects of local somatothermal stimulation preconditioning on the right Qimen (LR14) on hepatic I/R injury in rats. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups. The rats were preconditioned with thermal tolerance study, which included one dose of local somatothermal stimulation (LSTS) on right Qimen (LR14) at an interval of 12 h, followed by hepatic ischemia for 60 min and then reperfusion for 60 min. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been used to assess the liver functions, and liver tissues were taken for the measurements such as malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxidase dismutase (SOD), and myeloperoxidase (MPO). Results The results show that the plasma ALT and AST activities were higher in the I/R group than in the control group. In addition, the plasma ALT and AST activities decreased in the groups that received LSTS. The hepatic SOD levels reduced significantly by I/R injury. Moreover, the hepatic MPO activity significantly increased by I/R injury while it decreased in the groups given LSTS. Conclusions Our findings show that LSTS provides a protective effects on the liver from the I/R injury. Therefore, LSTS might offer an easy and inexpensive intervention for patients who have suffered from I/R of the liver especially in the process of hepatotomy and hepatic transplantation.

2014-01-01

201

Emulsified Isoflurane Preconditioning Reduces Lung Injury Induced By Hepatic Ischemia/Reperfusion in Rats  

PubMed Central

Objective: To investigate whether emulsified isoflurane preconditioning could reduce lung injury induced by hepatic I/R in rats and its mechanism. Materials and methods: 32 pentobarbital-anesthetized Sprague-Dawley rats were equally randomized into four groups: laparotomy group (Sham group), hepatic I/R and normal saline infusion group (I/R+S group), I/R and lipid vehicle infusion (I/R+V group), or I/R and 8% emulsified isoflurane infusion (I/R+E group) at the rate of 8 ml·kg-1·h-1 for 30 min. Blood supply of the hepatic artery and portal vein to the left and the median liver lobes was occluded for 90 min after 30-min washout time. Reperfusion was allowed to proceed for 4 h before sacrifice of the animals. Lung injury was observed histologically. Neutrophil infiltration and TNF-? concentration in serum and lung were measured. Changes of wet-to-dry weight ratios in lung tissue, ICAM-1 expression and NF-?B activity in lung after hepatic I/R were determined. Results: Compared with I/R+S or I/R+V group, emulsified isoflurane preconditioning reduced hepatic I/R-induced lung histologic injury and inhibited the increase of myeloperoxidase (MPO) activity in the lung tissue markedly (5.5±1.37 and 5.22±1.33 vs 3.81±1.62 U/g, P<0.05). In addition, both serum and lung tissue TNF-? levels were reduced in I/R+E group (104.58±31.40 and 94.60±22.23 vs 72.44±17.28 pg/ml, P<0.05; 393.51±88.22 and 405.46±102.87 vs 292.62±74.56 pg/ml, P<0.01). Emulsified isoflurane preconditioning also inhibited the increase of ICAM-1 expression (0.79±0.17 and 0.84±0.24 vs 0.62±0.21, P<0.05) and NF-?B translocation (4.93±0.48 and 4.76±0.57 vs 4.01±0.86, P<0.05) in the lung tissue markedly. Conclusions: Emulsified isoflurane preconditioning markedly attenuated hepatic I/R-induced lung injury in rats, which may be hopefully applied to the clinical treatment of organ injury caused by hepatic surgery, transplantation or hemorrhagic shock.

Lv, Xin; Wang, Zhen-meng; Huang, Sheng-dong; Song, Shao-hua; Wu, Fei-xiang; Yu, Wei-feng

2011-01-01

202

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis  

PubMed Central

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Zhao, Xin; Deng, Bo; Xu, Xue-Yan; Yang, Shi-Jun; Zhang, Tao; Song, Yi-Jun; Liu, Xiao-Ting; Wang, Yue-Qi; Cai, Da-Yong

2013-01-01

203

Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes  

PubMed Central

Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating ? cell duress. To identify genes/mechanisms involved with diabeto-genesis at the ? cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of ? cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility.

Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Ake; Hessner, Martin J.

2014-01-01

204

Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes.  

PubMed

Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating ? cell duress. To identify genes/mechanisms involved with diabetogenesis at the ? cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of ? cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

Bogdani, Marika; Henschel, Angela M; Kansra, Sanjay; Fuller, Jessica M; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Ake; Hessner, Martin J

2013-02-01

205

Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats  

PubMed Central

Objective: The aim of the present study was to investigate the renal protective effect of Adenanthera pavonina (A. pavonina) seed aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The renal protective effect of A. pavonina seed aqueous extract (APSAE) was studied in STZ-induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day) was given daily to diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin, creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c), and urine parameters such as urine protein and albumin were examined. Kidney histopathology was also done. Results: After 13 weeks of treatment, in STZ-induced diabetic rats, severe hyperglycemia was developed, with marked increase in proteinuria and albuminuria. However, APSAE treatment significantly reduced proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats. Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

Pandhare, Ramdas; Sangameswaran, Balakrishnan

2012-01-01

206

Reduced conduction reserve of the propagating cardiac impulse in the diabetic rat heart: a model study.  

PubMed

Conduction velocity is dependent on two main factors: intercellular electrical coupling and cellular electrical excitability. There is significant redundancy, 'conduction reserve', in these parameters such that significant reduction in the conduction velocity of the action potential requires either a severe change in one of these parameters or a combined change in both parameters. Studies in diabetic rat hearts have shown a significant reduction in the conduction reserve and it was hypothesized that this is mainly due to the lateralization of the gap junction protein connexin 43 (Cx43). To gain a better understanding of the effect of reduced intercellular coupling, a rat ventricle myocyte model was used to simulate propagation along a strand of cells. Simulations were performed to assess the effect of reduction of intercellular conductance on the conduction velocity. As the conductance of the gap junction decreased a significant reduction in the conduction velocity was observed. The relationship between conduction velocity and intercellular coupling became steeper with decreasing coupling, such that conduction velocity became increasingly sensitive to further uncoupling. This is consistent with experimental results, in which application of the gap junction uncoupler heptanol caused a larger conduction slowing in diabetic hearts than in controls. PMID:19164067

Ghaly, H; Boyle, P; Vigmond, E; Nygren, A

2008-01-01

207

Fructose-rich diet leads to reduced aerobic capacity and to liver injury in rats  

PubMed Central

The main purpose of this research was to investigate the alterations in the aerobic capacity and appearance of metabolic alterations in Wistar rats fed on fructose-rich diet. We separated twenty-eight rats into two groups according to diet: a control group (C) (balanced diet) and a fructose-rich diet group (F). The animals were fed these diets for 60 d (d 120 to 180). We performed insulin, glucose as well as a minimum lactate test, at d 120 and 180. At the end of the experiment, sixteen animals were euthanized, and the following main variables were analysed: aerobic capacity, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, serum and liver triglyceride concentrations, serum and liver thiobarbituric acid reactive substance (TBARS) concentrations, serum and liver catalase and superoxide dismutase (SOD) activity and haematoxylin-eosin histology (HE) in hepatocytes. The remaining twelve animals were submitted to an analysis of their hepatic lipogenic rate. The animals fed a fructose-rich diet exhibited a reduction in aerobic capacity, glucose tolerance and insulin sensitivity and increased concentrations of triglycerides and TBARS in the liver. Catalase and SOD activities were reduced in the livers of the fructose-fed animals. In addition, the serum AST/ALT ratio was higher than that of the C group, which indicates hepatic damage, and the damage was confirmed by histology. In conclusion, the fructose-rich diet caused significant liver damage and a reduction in insulin sensitivity in the animals, which could lead to deleterious metabolic effects.

2012-01-01

208

Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain  

PubMed Central

Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy (HIE). Methods This investigation employed primary cortical neuron cultures derived from neonatal rats subjected to oxygen and glucose deprivation (OGD) and a well-established neonatal rat hypoxia-ischemia model. Results HI caused brain tissue loss and impaired sensorimotor function and spatial memory while SP significantly reduced brain damage and improved neurological performance. These neuroprotective effects of SP are likely the result of improved cerebral metabolism as demonstrated by maintaining ATP levels and preventing an increase in intracellular reactive oxygen species (ROS) levels. SP treatment also decreased levels of Bax, a death signal for immature neurons, blocked caspases-3 activation, and activated a key survival signaling kinase, Akt, both in vitro and in vivo. Conclusion SP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.

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

2013-01-01

209

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

PubMed

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

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

2006-01-01

210

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

PubMed Central

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.

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

2014-01-01

211

Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans  

PubMed Central

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. 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 FB1 (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 FB1 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, FB1 control, FB1 + 2% NS or absolute control group. FB1 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?1) or placebo (1.5 g day?1) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB1 biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analyzed (n = 186) had detectable levels of FB1. Median urinary FB1 levels were significantly (p < 0.05) decreased by > 90% in the high dose NS group (3 g day?1) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB1 (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 FB1. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB1 is suspected to be a dietary risk factor for HCC and esophageal cancer in humans.

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

212

Electromagnetic pulse reduces free radical generation in rat liver mitochondria in vitro.  

PubMed

Non-ionizing radiation electromagnetic pulse (EMP) is generally recorded to induce the generation of free radicals in vivo. Though mitochondria are the primary site to produce free radicals, a rare report is designed to directly investigate the EMP effects on free radical generation at mitochondrial level. Thus the present work was designed to study how EMP induces free radical generation in rat liver mitochondria in vitro using electron paramagnetic resonance technique. Surprisingly, our data suggest that EMP prevents free radical generation by activating antioxidant enzyme activity and reducing oxygen consumption and therefore free radical generation. Electron spin resonance measurements clearly demonstrate that disordering of mitochondrial lipid fluidity and membrane proteins mobility are the underlying contributors to this decreased oxygen consumption. Therefore, our results suggest that EMP might hold the potentiality to be developed as a non-invasive means to benefit certain diseases. PMID:23330577

Wang, C; Zhou, H; Peng, R; Wang, L; Su, Z; Chen, P; Wang, S; Wang, S; Liu, Y; Cong, J; Wu, K; Hu, X; Fan, E

2013-04-01

213

Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats.  

PubMed

We investigated the effects of silymarin and naringenin in counteracting arsenic-induced hepatic oxidative stress post exposure. Male wistar rats were chronically exposed to sodium arsenite for eight months followed by oral treatment with silymarin and naringenin (50 mg/kg each) for 15 consecutive days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic GSH levels, SOD and catalase activities and an increase in GST and TBARS levels after arsenic administration. Silymarin or naringenin administration increased GSH levels and was beneficial in the recovery of altered SOD and catalase activity besides significantly reducing blood and tissue arsenic concentration. Our results point to the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to arsenic. These flavonoids can be incorporated into the diet or co-supplemented during chelation treatment, and thus may afford a protective effect against arsenite-induced cytotoxicity. PMID:20719385

Jain, Anshu; Yadav, Abhishek; Bozhkov, A I; Padalko, V I; Flora, S J S

2011-05-01

214

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

PubMed Central

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.

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

1995-01-01

215

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

PubMed Central

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 and sprouting, as shown by histological analysis, reduced mechanical allodynia, evaluated by Von Frey filaments, and inhibited dorsal root ganglia activation. These results were supported by the evidence that MCs in granuloma were mainly degranulated and closely localized near nerve fibres and PEA significantly reduced MC degranulation and nerves fibre formation. These findings are the first evidence that PEA, by the modulation of MC activation, controls pain perception in an animal model of chronic inflammation, suggesting its potential use for the treatment of all those painful conditions in which MC activation is an initial key step.

2011-01-01

216

Eucalyptol, an essential oil, reduces contractile activity in rat cardiac muscle.  

PubMed

Eucalyptol is an essential oil that relaxes bronchial and vascular smooth muscle although its direct actions on isolated myocardium have not been reported. We investigated a putative negative inotropic effect of the oil on left ventricular papillary muscles from male Wistar rats weighing 250 to 300 g, as well as its effects on isometric force, rate of force development, time parameters, post-rest potentiation, positive inotropic interventions produced by Ca2+ and isoproterenol, and on tetanic tension. The effects of 0.3 mM eucalyptol on myosin ATPase activity were also investigated. Eucalyptol (0.003 to 0.3 mM) reduced isometric tension, the rate of force development and time parameters. The oil reduced the force developed by steady-state contractions (50% at 0.3 mM) but did not alter sarcoplasmic reticulum function or post-rest contractions and produced a progressive increase in relative potentiation. Increased extracellular Ca2+ concentration (0.62 to 5 mM) and isoproterenol (20 nM) administration counteracted the negative inotropic effects of the oil. The activity of the contractile machinery evaluated by tetanic force development was reduced by 30 to 50% but myosin ATPase activity was not affected by eucalyptol (0.3 mM), supporting the idea of a reduction of sarcolemmal Ca2+ influx. The present results suggest that eucalyptol depresses force development, probably acting as a calcium channel blocker. PMID:15761626

Soares, M C M S; Damiani, C E N; Moreira, C M; Stefanon, I; Vassallo, D V

2005-03-01

217

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

PubMed Central

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.

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

1984-01-01

218

Ebselen Alters Mitochondrial Physiology and Reduces Viability of Rat Hippocampal Astrocytes  

PubMed Central

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca2+ concentration ([Ca2+]c), the mitochondrial free-Ca2+ concentration ([Ca2+]m), and mitochondrial membrane potential (?m) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca2+]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca2+]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ?m and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

Santofimia-Castano, Patricia; Salido, Gines M.

2013-01-01

219

Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.  

PubMed

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (?m) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ?m and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function. PMID:23496767

Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

2013-04-01

220

Pomegranate (Punica granatum) juice reduces oxidative injury and improves sperm concentration in a rat model of testicular torsion-detorsion  

PubMed Central

The present study aimed to evaluate the effect of pomegranate juice (PJ) on oxidative stress (OS) and sperm concentration in a rat model of testicular torsion-detorsion. A total of 21 Wistar albino rats were randomly divided into three groups, each consisting of seven rats, as follows: i) control group, which underwent sham surgery; ii) ischemia/reperfusion (I/R) group, designed to determine the effects of the testicular torsion-detorsion process on rats; and iii) PJ+I/R group, designed to evaluate the effect of PJ on the OS and sperm cell concentrations induced by the torsion-detorsion process. In the PJ+I/R group, the rats were given 0.4 ml/day PJ orally over a period of eight weeks prior to surgery. Ipsilateral orchiectomy was carried out and 5-cm3 blood samples were obtained from the inferior vena cava of all rats. Biochemical analyses were performed to calculate the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the testicular tissue and serum. The concentrations of spermatids, spermatocytes and spermatogonia in the seminiferous tubules were assessed using histopathological methods. Serum and tissue SOD and MDA levels were significantly higher in rats from the I/R group compared with the control group (P<0.001). PJ treatment significantly decreased the SOD and MDA levels in both the serum and testicular tissue of the rats (P<0.001). The spermatid, spermatocyte and spermatogonia concentrations were significantly reduced in the I/R group compared with the control group (P<0.001). PJ treatment significantly improved the concentrations of spermatids, spermatocytes and spermatogonia compared with those in the I/R group (P=0.008). The experimentally established testicular torsion-detorsion model led to OS in the rat testes. Daily consumption of PJ prior to surgery reduced OS parameters and improved sperm cell concentrations.

ATILGAN, DOGAN; PARLAKTAS, BEKIR; ULUOCAK, NIHAT; GENCTEN, YUSUF; ERDEMIR, FIKRET; OZYURT, HUSEYIN; ERKORKMAZ, UNAL; ASLAN, HUSEYIN

2014-01-01

221

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

PubMed Central

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?

2012-01-01

222

Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats.  

PubMed

Osteoinduction is the formation of ectopic bone that follows implantation of demineralized allogeneic bone matrix (DABM) and is believed to be secondary to the release of associated inductive factors from bone matrix. To clarify the role of vitamin D in osteoinduction, we implanted DABM from vitamin D-deficient rats (-D rats) into normal rats (+D rats). Because mitogens and osteocalcin might be involved in osteoinduction, these were measured. Mitogenic activity in extracts from mineralized allogeneic bone matrix (ABM) and DABM from both +D and -D rats was determined with an assay that utilizes monolayer cultures of embryonic chick calvarial cells. Osteocalcin in serum and DABM was measured by radioimmunoassay. DABM from -D rats did not promote osteoinduction as effectively as DABM from +D rats. Resorption of implant matrix from -D rats was diminished compared with resorption of matrix from +D rats (P less than 0.01), and the decrease was attributed to a corresponding decrease in the number of osteoclasts in the implants (P less than 0.02). Bone formation (P less than 0.01) and total implant mineralization (P less than 0.001) were significantly reduced in implants from -D rats, and the reductions corresponded with a decline in the number of osteoblasts (P less than 0.05). Mitogenic activity in DABM from +D rats was only slightly decreased as compared with activity in ABM, but DABM from -D rats contained significantly less activity (P less than 0.001). No mitogenic activity was identified in implants of DABM from either +D or -D rats 3 wk after implantation. Serum osteocalcin was significantly higher in -D as compared with +D animals. In contrast, the concentrations of osteocalcin in DABM from the two groups of animals were not significantly different from each other. These findings indicate that the diminished osteoinductive activity of DABM from -D rats results from deficiency of one or more mitogenic factors that are essential for inducing the proliferation and differentiation of bone cells at the implant site and that osteocalcin does not play a role in this regard. PMID:3260604

Turner, R T; Farley, J; Vandersteenhoven, J J; Epstein, S; Bell, N H; Baylink, D J

1988-07-01

223

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

PubMed

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

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

2014-08-01

224

Genetic regulation of canine skeletal traits: trade-offs between the hind limbs and forelimbs in the fox and dog  

Microsoft Academic Search

Synopsis Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs

Anastasia V. Kharlamova; Lyudmila N. Trut; David R. Carrier; Kevin Chase; Karl G. Lark

2007-01-01

225

Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats  

PubMed Central

AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury. METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 ?g/kg, i.p.), prior to ischemic injury and AGM treatment, and examined histologically and immunostained. Another set of experiments was run to study vascular permeability of the stomach using Evan’s blue dye. RESULTS: AGM markedly reduced Evan’s blue dye extravasation (3.58 ± 0.975 ?g/stomach vs 1.175 ± 0.374 ?g/stomach, P < 0.05), VEGF (36.87 ± 2.71 pg/100 mg protein vs 48.4 ± 6.53 pg/100 mg protein, P < 0.05) and MCP-1 tissue level (29.5 ± 7 pg/100 mg protein vs 41.17 ± 10.4 pg/100 mg protein, P < 0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals. The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen. CONCLUSION: AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K.

Masri, Abeer A Al; Eter, Eman El

2012-01-01

226

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

USGS Publications Warehouse

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.

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

2013-01-01

227

Genetic regulation of canine skeletal traits: trade-offs between the hind limbs and forelimbs in the fox and dog.  

PubMed

Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, approximately 30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2-2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in other tetrapod taxa. PMID:18458753

Kharlamova, Anastasia V; Trut, Lyudmila N; Carrier, David R; Chase, Kevin; Lark, Karl G

2007-09-01

228

Ionizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defects.  

PubMed

Several lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation. We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels. Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study. PMID:18722365

Derradji, Hanane; Bekaert, Sofie; De Meyer, Tim; Jacquet, Paul; Abou-El-Ardat, Khalil; Ghardi, Myriam; Arlette, Michaux; Baatout, Sarah

2008-10-15

229

Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids.  

PubMed

Glucocorticoids (GC)--corticosterone (CORT) in rodents and cortisol in primates--are stress-induced hormones secreted by adrenal glands that interact with the hypothalamic pituitary axis. High levels of cortisol in humans are observed in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), as well as in diabetes, post-traumatic stress syndrome, and major depression. Experimental models of diabetes in rats and mice have demonstrated that reduction of CORT reduces learning and memory deficits and attenuates loss of neuronal viability and plasticity. In contrast to the negative associations of elevated GC levels, CORT is moderately elevated in dietary restriction (DR) paradigms which are associated with many healthy anti-aging effects including neuroprotection. We demonstrate here in rats that ablating CORT by adrenalectomy (ADX) with replenishment to relatively low levels (30% below that of controls) prior to the onset of a DR regimen (ADX-DR) followed by central administration of the neurotoxin, kainic acid (KA), significantly attenuates learning deficits in a 14-unit T-maze task. The performance of the ADX-DR KA group did not differ from a control group (CON) that did not receive KA and was fed ad libitum (AL). By contrast, the sham-operated DR (SHAM-DR KA) group, SHAM-AL KA group, and ADX-AL KA group demonstrated poorer learning behavior in this task compared to the CON group. Stereological analysis revealed equivalent DR-induced neuroprotection in the SH-DR KA and ADX-DR KA groups, as measured by cell loss in the CA2/CA3 region of the hippocampus, while substantial cell loss was observed in SH-AL and ADX-AL rats. A separate set of experiments was conducted with similar dietary and surgical treatment conditions but without KA administration to examine markers of neurotrophic activity, brain-derived neurotrophic factor (BDNF), transcriptions factors (pCREB), and chaperone proteins (HSP-70). Under these conditions, we noted elevations in both BDNF and pCREB in ADX DR rats compared to the other groups; whereas, HSP-70, was equivalently elevated in ADX-DR and SH-DR groups and was higher than observed in both SH-AL and ADX-AL groups. These results support findings that DR protects hippocampal neurons against KA-induced cellular insult. However, this neuroprotective effect was further enhanced in rats with a lower-than control level of CORT resulting from ADX and maintained by exogenous CORT supplementation. Our results then suggest that DR-induced physiological elevation of GC may have negative functional consequences to DR-induced beneficial effects. These negative effects, however, can be compensated by other DR-produced cellular and molecular protective mechanisms. PMID:22226488

Qiu, Guang; Spangler, Edward L; Wan, Ruiqian; Miller, Marshall; Mattson, Mark P; So, Kwok-Fai; de Cabo, Rafael; Zou, Sige; Ingram, Donald K

2012-10-01

230

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

PubMed

The present study was aimed to observe the protective effect of exogenous hydrogen sulfide (H2S) 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(-1)·d(-1)), middle (10 ?mol·kg(-1)·d(-1)) or high (100 ?mol·kg(-1)·d(-1)) 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(-1)·d(-1) 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 H2S 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 H2S 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 H2S 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

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

2014-06-25

231

Reduced Inflammatory Phenotype in Microglia Derived from Neonatal Rat Spinal Cord versus Brain  

PubMed Central

Microglia are the primary immune cells of the central nervous system (CNS). Membrane bound sensors on their processes monitor the extracellular environment and respond to perturbations of the CNS such as injury or infection. Once activated, microglia play a crucial role in determining neuronal survival. Recent studies suggest that microglial functional response properties vary across different regions of the CNS. However, the activation profiles of microglia derived from the spinal cord have not been evaluated against brain microglia in vitro. Here, we studied the morphological properties and secretion of inflammatory and trophic effectors by microglia derived from the brain or spinal cord of neonatal rats under basal culture conditions and after activation with lipopolysaccharide (LPS). Our results demonstrate that spinal microglia assume a less inflammatory phenotype after LPS activation, with reduced release of the inflammatory effectors tumor necrosis factor alpha, interleukin-1 beta, and nitric oxide, a less amoeboid morphology, and reduced phagocytosis relative to brain-derived microglia. Phenotypic differences between brain and spinal microglia are an important consideration when evaluating anti-inflammatory or immunomodulatory therapies for brain versus spinal injury.

Baskar Jesudasan, Sam Joshva; Todd, Kathryn G.; Winship, Ian R.

2014-01-01

232

Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats  

PubMed Central

Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates cell death by interrupting classic pathways of apoptosis. Intracerebral hemorrhage (ICH) is a devastating acute neurological disorder, without effective treatment, in which a significant loss of neuronal cells is thought to occur by apoptosis. In this study, we evaluated whether TUDCA can reduce brain injury and improve neurological function after ICH in rats. Administration of TUDCA before or up to 6 h after stereotaxic collagenase injection into the striatum reduced lesion volumes at 2 days by as much as 50%. Apoptosis was ?50% decreased in the area immediately surrounding the hematoma and was associated with a similar inhibition of caspase activity. These changes were also associated with improved neurobehavioral deficits as assessed by rotational asymmetry, limb placement, and stepping ability. Furthermore, TUDCA treatment modulated expression of certain Bcl-2 family members, as well as NF-?B activity. In addition to its protective action at the mitochondrial membrane, TUDCA also activated the Akt-1/protein kinase B? survival pathway and induced Bad phosphorylation at Ser-136. In conclusion, reduction of brain injury underlies the wide-range neuroprotective effects of TUDCA after ICH. Thus, given its clinical safety, TUDCA may provide a potentially useful treatment in patients with hemorrhagic stroke and perhaps other acute brain injuries associated with cell death by apoptosis.

Rodrigues, Cecilia M. P.; Sola, Susana; Nan, Zhenhong; Castro, Rui E.; Ribeiro, Paulo S.; Low, Walter C.; Steer, Clifford J.

2003-01-01

233

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

PubMed

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

Wang, Yun; Zhang, Zhong-Ze; Wu, Yun; Zhan, Jia; He, Xiang-Hu; Wang, Yan-Lin

2013-01-01

234

Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion.  

PubMed

Lipids may serve as coupling factors in K(ATP)-independent glucose sensing in beta-cells. We have previously demonstrated that beta-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether beta-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in K(ATP)-independent glucose sensing has been perturbed. Thus, beta-cell lipase activity is involved in GSIS, emphasizing the important role of beta-cell lipid metabolism for insulin secretion. PMID:14693706

Mulder, Hindrik; Yang, Shumin; Winzell, Maria Sörhede; Holm, Cecilia; Ahrén, Bo

2004-01-01

235

The addition of whole soy flour to cafeteria diet reduces metabolic risk markers in wistar rats  

PubMed Central

Background Soybean is termed a functional food because it contains bioactive compounds. However, its effects are not well known under unbalanced diet conditions. This work is aimed at evaluating the effect of adding whole soy flour to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity markers in rats. Methods In this study, 30 male adult Wistar rats were used, distributed among three groups (n?=?10): AIN-93 M diet, cafeteria diet (CAF) and cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were measured: food intake; weight gain; serum concentrations of triglycerides, total cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS); humidity and lipid fecal content; weight and fat of the liver. The villous height, the crypt depth and the thickness of the duodenal and ileal circular and longitudinal muscle layers of the animals were also measured. Results There was a significant reduction in the food intake in the CAF group. The CAFS showed lower serum concentrations of triglycerides and serum TBARS and a lower percentage of hepatic fat, with a corresponding increase in thickness of the intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c and villous height. The addition of soy did not promote any change in these parameters. Conclusions The inclusion of whole soy flour in a high-fat diet may be helpful in reducing some markers of metabolic risk; however, more studies are required to clarify its effects on unbalanced diets.

2013-01-01

236

Reduced ghrelin production induced anorexia after rat gastric ischemia and reperfusion.  

PubMed

The gastrointestinal (GI) tract is one of the most susceptible organs to ischemia. We previously reported altered gastric motility after gastric ischemia and reperfusion (I/R). However, there have also been few reports of alterations in the eating behavior after gastric I/R. Ghrelin is a GI peptide that stimulates food intake and GI motility. Although ghrelin itself has been demonstrated to attenuate the mucosal injuries induced by gastric I/R, the endogenous ghrelin dynamics after I/R has not yet been elucidated. The present study was designed to investigate the relationship between food intake and the ghrelin dynamics after gastric I/R. Wistar rats were exposed to 80-min gastric ischemia, followed by 12-h or 48-h reperfusion. The food intake, plasma ghrelin levels, gastric preproghrelin mRNA expression levels, and the histological localization of ghrelin-immunoreactive cells were evaluated. The effect of exogenous ghrelin on the food intake after I/R was also examined. Food intake, the plasma ghrelin levels, the count of ghrelin-immunoreactive cells corrected by the percentage areas of the remaining mucosa, and the expression levels of preproghrelin mRNA in the stomach were significantly reduced at 12 h and 48 h after I/R compared with the levels in the sham-operated rats. Intraperitoneal administration of ghrelin significantly reversed the decrease of food intake after I/R. These data show that gastric I/R evoked anorexia with decreased plasma ghrelin levels and ghrelin production, which appears to be attributable to the I/R-induced gastric mucosal injuries. The decrease in the plasma ghrelin levels may have been responsible for the decreased food intake after gastric I/R. PMID:22114115

Mogami, Sachiko; Suzuki, Hidekazu; Fukuhara, Seiichiro; Matsuzaki, Juntaro; Kangawa, Kenji; Hibi, Toshifumi

2012-02-01

237

Rosuvastatin reduces neointima formation in a rat model of balloon injury  

PubMed Central

Background Processes of restenosis, following arterial injury, are complex involving different cell types producing various cytokines and enzymes. Among those enzymes, smooth muscle cell-derived matrix metalloproteinases (MMPs) are thought to take part in cell migration, degrading of extracellular matrix, and neointima formation. MMP-9, also known as gelatinase B, is expressed immediately after vascular injury and its expression and activity can be inhibited by statins. Using an established in vivo model of vascular injury, we investigated the effect of the HMG-CoA reductase inhibitor rosuvastatin on MMP-9 expression and neointima formation. Materials and methods 14-week old male Sprague Dawley rats underwent balloon injury of the common carotid artery. Half of the animals received rosuvastatin (20 mg/kg body weight/day) via oral gavage, beginning 3 days prior to injury. Gelatinase activity and neointima formation were analyzed 3 days and 14 days after balloon injury, respectively. 14 days after vascular injury, proliferative activity was assessed by staining for Ki67. Results After 14 days, animals in the rosuvastatin group showed a decrease in total neointima formation (0.194 ± 0.01 mm2 versus 0.124 ± 0.02 mm2, p < 0.05) as well as a reduced intima/media ratio (1.26 ± 0.1 versus 0.75 ± 0.09, p < 0.05). Balloon injury resulted in increased activity of MMP-9 3 days after intervention for both rosuvastatin treated animals and controls with no significant difference observed between the groups. There was a trend towards a reduction in the number of Ki67-positive cells 14 days after injury. Conclusions Rosuvastatin attenuates neointima formation without affecting early MMP-9 activity in a rat model of vascular injury.

2010-01-01

238

Blockade of central orexin 2 receptors reduces arterial pressure in spontaneously hypertensive rats.  

PubMed

Orexins can raise arterial pressure and sympathetic activity and are involved in tonic and phasic control of cardiovascular homeostasis. We hypothesized that elevated central orexinergic activity contributes to the maintenance of hypertension in spontaneously hypertensive rats (SHRs). We examined this hypothesis by suppressing central orexinergic activity in SHRs and Wistar-Kyoto rats (WKYs) with specific antagonists or antibodies against orexin 1 (OX1R) and 2 receptors (OX2R). Intracerebroventricular administration of an OX1R antagonist, SB-334867 (30 and 100 nmol), induced no significant change in mean arterial pressure (MAP) and heart rate (HR) in SHRs and WKYs except that at 100 nmol it reduced HR in WKYs. In contrast, an OX2R antagonist, TCS-OX2-29 (3-30 nmol) induced long-lasting reductions of MAP and HR in SHRs (21 ± 3 mmHg and 22 ± 2 beats min(-1) at 30 nmol), but not in WKYs. Intracerebroventricular anti-OX2R IgG, but not anti-OX1R IgG or non-immune goat IgG, significantly lowered MAP and HR in SHRs. None of the three IgGs affected MAP or HR in WKYs. The OX2R protein level in the rostral ventrolateral medulla (RVLM) was lower in SHRs than in WKYs, whereas no differences were found between SHRs and WKYs in the paraventricular hypothalamic nucleus, dorsomedial-perifornical hypothalamic area or caudal nucleus tractus solitarii. The OX1R protein levels in these four regions did not differ between SHRs and WKYs. Injection of TCS-OX2-29 (50 pmol) into the RVLM produced a larger reduction of MAP in SHRs than in WKYs. We conclude that elevated OX2R-mediated activity in the brain, especially in the RVLM, may contribute to hypertension in SHRs. PMID:23525245

Lee, Yen-Hsien; Dai, Yu-Wen E; Huang, Shang-Cheng; Li, Tzu-Ling; Hwang, Ling-Ling

2013-07-01

239

Bortezomib Reduces Neointimal Hyperplasia in a Rat Carotid Artery Injury Model  

PubMed Central

Background and Objectives The ubiquitin-proteasome system is the major intracellular protein degradation pathway in the eukaryotic cells. Bortezomib inhibits 26S proteasome-induced I-?B? degradation and suppresses nuclear factor-kappa B (NF-?B) activation. We examined the effect of bortezomib on neointima formation after of a rat carotid artery balloon injury. Materials and Methods After carotid artery balloon denudation, bortezomib was immediately administered by tail vein injection (systemic treatment) and by using an F-127 pluronic gel (perivascular treatment). Two weeks after the injury, we compared the degree of neointima formation in the carotid artery and the tissue expression patterns of NF-?B and I-?B?. Results The systemic treatment group exhibited a 29% reduction in neointima volume at two weeks after the balloon injury. On the western blot analysis, the bortezomib group exhibited an increased I-?B? expression, which suggested the inhibition of I-?B? degradation. On immunofluorescence analysis, the nuclear import of NF-?B was clearly decreased in the systemic bortezomib group. The perivascular bortezomib treatment group exhibited a significant reduction in the neointimal area (0.21±0.06 mm2 vs. 0.06±0.01 mm2, p<0.05), the neointima/media area ratio (1.43±0.72 vs. 0.47±0.16, p<0.05) and the % area stenosis (45.5±0.72% vs. 14.5±0.05%, p<0.05) compared with the control group. In situ vascular smooth muscle cell proliferation at 2 days after the injury was significantly inhibited (24.7±10.9% vs. 10.7±4.7%, p<0.05). Conclusion Bortezomib suppressed NF-?B activation through the inhibition of I-?B? degradation, and significantly reduced neointima formation in a rat carotid artery injury model. These data suggested that bortezomib represented a new potent therapeutic agent for the prevention of restenosis.

Kim, Song Yi; Choi, Joon Hyeok; Joo, Seung Jae; Kim, Dong Woon; Cho, Myeong Chan

2013-01-01

240

Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats.  

PubMed

Several studies have demonstrated that treatment with antioxidants improves hypertension in spontaneously hypertensive rats (SHR). Because our laboratory has shown that renal infiltration of immune cells plays a role in the development of hypertension (Rodriguez-Iturbe B, Quiroz Y, Nava M, Bonet L, Chavez M, Herrera-Acosta J, Johnson RJ, and Pons HA. Am J Physiol Renal Physiol 282: F191-F201, 2002), we did the present studies to define whether the antihypertensive effect of antioxidants was associated with an improvement in renal inflammation. Melatonin was administered as an antioxidant. For 6 wk, melatonin was added to the drinking water (10 mg/100 ml) given to a group of SHR (SHR-Mel; n = 10), and we compared them with groups of untreated SHR (n = 10) and Wistar-Kyoto (WKY) control rats (n = 10). Hypertension became increasingly severe in the SHR group [195 +/- 14.3 (SD) mmHg at the end of the experiment] and improved in the SHR-Mel group (149 +/- 20.4 mmHg, P < 0.001) in association with a 40-60% reduction in the renal infiltration of lymphocytes, macrophages, and angiotensin II-positive cells. Intracellular superoxide and renal malondialdehyde content were reduced by melatonin treatment as was the immunohistological expression of the 65-kDA DNA-binding subunit of NF-kappaB. We conclude that melatonin treatment ameliorates hypertension in SHR in association with a reduction in interstitial renal inflammation. Decreased activation of NF-kappaB, likely resulting from a reduction in local oxidative stress, may play a role in the suppression of renal immune infiltration and, thereby, in the antihypertensive effects of melatonin. PMID:12441307

Nava, Mayerly; Quiroz, Yasmir; Vaziri, Nosratola; Rodriguez-Iturbe, Bernardo

2003-03-01

241

Reduced Ribosomal Protein S6 Phosphorylation following Progressive Resistance Exercise in Growing Adolescent Rats  

PubMed Central

The purpose of the present study was to investigate moderate intensity progressive resistance exercise (PRE) in growing adolescent rats and its effect on muscle hypertrophy (defined as an increase in fiber cross-sectional area). We hypothesized that in adolescent animals moderate intensity PRE would increase: 1) fiber cross-sectional area (CSA); 2) myosin heavy chain (MyHC) content; and 3) expression and phosphorylation of cell signaling molecules involved in translational regulation, compared to age-matched sedentary controls (SED). In the PRE group, three-week old male rats were trained to climb a vertical ladder as a mode of PRE training such that by 10 weeks, all animals in the PRE group had progressed to carry an additional 80% of body weight per climb. In agreement with our hypotheses, we observed that 10 weeks of moderate PRE in adolescent animals was sufficient to increase CSA of muscle fibers and increase MyHC content. Average muscle fiber CSA increased by greater than 10% and total MyHC content increased by 35% (p<0.05) in the PRE group compared to SED animals. Concurrently, we investigated sustained changes in the expression and phosphorylation of key signaling molecules that are previously identified regulators of hypertrophy in adult animal models. Contrary to our hypotheses, expression and phosphorylation of the translational regulators mTOR and Akt were not increased in the PRE group. In addition, we observed that the ratio of phosphorylated-to-unphosphorylated ribosomal protein S6 (rpS6) was reduced over six-fold in PRE animals (p<0.05) and total rpS6 protein levels were unchanged between PRE and sedentary animals (p>0.05). We conclude that moderate intensity PRE is sufficient to induce muscle hypertrophy in adolescent animals while the signaling mechanisms associated with muscle hypertrophy may differ between growing adolescents and adults.

Hellyer, Nathan J.; Nokleby, Jessica J.; Thicke, Bethany M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

2011-01-01

242

Reduced ribosomal protein s6 phosphorylation after progressive resistance exercise in growing adolescent rats.  

PubMed

The purpose of this study was to investigate moderate intensity progressive resistance exercise (PRE) in growing adolescent rats and its effect on muscle hypertrophy (defined as an increase in fiber cross-sectional area [CSA]). We hypothesized that in adolescent animals moderate intensity PRE would increase (a) fiber CSA; (b) myosin heavy chain (MyHC) content; and (c) expression and phosphorylation of cell signaling molecules involved in translational regulation, compared with that in age-matched sedentary (SED) controls. In the PRE group, 3-week-old male rats were trained to climb a vertical ladder as a mode of PRE training such that by 10 weeks all animals in the PRE group had progressed to carry an additional 80% of their body weight per climb. In agreement with our hypotheses, we observed that 10 weeks of moderate PRE in adolescent animals was sufficient to increase the CSA of muscle fibers and increase MyHC content. The average muscle fiber CSA increased by >10%, and the total MyHC content increased by 35% (p < 0.05) in the PRE group compared with that in the SED animals. Concurrently, we investigated sustained changes in the expression and phosphorylation of key signaling molecules that are previously identified regulators of hypertrophy in adult animal models. Contrary to our hypotheses, expression and phosphorylation of the translational regulators mammalian target of rapamycin and Akt were not increased in the PRE group. In addition, we observed that the ratio of phosphorylated-to-unphosphorylated ribosomal protein S6 (rpS6) was reduced over sixfold in PRE animals (p < 0.05) and that total rpS6 protein levels were unchanged between PRE and SED animals (p > 0.05). We conclude that moderate intensity PRE is sufficient to induce muscle hypertrophy in adolescent animals, whereas the signaling mechanisms associated with muscle hypertrophy may differ between growing adolescents and adults. PMID:22614147

Hellyer, Nathan J; Nokleby, Jessica J; Thicke, Bethany M; Zhan, Wen-Zhi; Sieck, Gary C; Mantilla, Carlos B

2012-06-01

243

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

PubMed

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

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

244

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

PubMed Central

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.

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

2007-01-01

245

Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves  

PubMed Central

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% NaHCO3 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.

Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo

2010-01-01

246

Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves.  

PubMed

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

Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo

2010-10-01

247

Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points.  

PubMed

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30-400 Hz), amplitude (30-200 ?A), and duration (0.5-2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80-140 Hz, 80-140 ?A, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 ?A, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement. PMID:23741044

Van Acker, Gustaf M; Amundsen, Sommer L; Messamore, William G; Zhang, Hongyu Y; Luchies, Carl W; Kovac, Anthony; Cheney, Paul D

2013-09-01

248

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys  

PubMed Central

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.

Umeda, Tatsuya; Seki, Kazuhiko; Sato, Masa-aki; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

2012-01-01

249

Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats  

PubMed Central

The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The “proarrhythmic” effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T1-T4), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias.

Lujan, Heidi L.; Palani, Gurunanthan; Zhang, Lijie

2010-01-01

250

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).  

PubMed

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate. PMID:8913326

Kanda, T; Kurokawa, M; Tamura, S; Nakamura, J; Ishii, A; Kuwana, Y; Serikawa, T; Yamada, J; Ishihara, K; Sasa, M

1996-01-01

251

Evidence that Memantine Reduces Chronic Tinnitus Caused by Acoustic Trauma in Rats  

PubMed Central

Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Increasing evidence suggests that tinnitus is caused by neuronal hyperactivity in auditory brain regions, either due to a decrease in synaptic inhibition or an increase in synaptic excitation. One drug investigated for the treatment of tinnitus has been the uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, although the evidence relating to it has been unconvincing to date. We re-investigated the effects of memantine on the behavioral manifestations of tinnitus induced by acoustic trauma (a 16-kHz, 110-dB pure tone presented unilaterally for 1?h) in rats. We used a conditioned lick suppression model in which lick suppression was associated with the perception of high frequency sound resembling tinnitus and a suppression ratio (SR) was calculated by comparing the number of licks in the 15-s period preceding the stimulus presentation (A) and the 15-s period during the stimulus presentation (B), i.e., SR?=?B/(A?+?B). Acoustic trauma resulted in a significant increase in the auditory brainstem-evoked response (ABR) threshold in the affected ear (P???0.0001) and a decrease in the SR compared to sham controls in response to 32?kHz tones in five out of eight acoustic trauma-exposed animals. A 5-mg/kg dose of memantine significantly reduced the proportion of these animals which exhibited tinnitus-like behavior (2/5 compared to 5/5; P???0.006), suggesting that the drug reduced tinnitus. These results suggest that memantine may reduce tinnitus caused by acoustic trauma.

Zheng, Yiwen; McNamara, Emily; Stiles, Lucy; Darlington, Cynthia L.; Smith, Paul F.

2012-01-01

252

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

Microsoft Academic Search

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

Scott E Krahl; Shayani S Senanayake; Adrian Handforth

2003-01-01

253

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...

254

Metformin and atorvastatin reduce adhesion formation in a rat uterine horn model.  

PubMed

The aim of the present study was to determine whether atorvastatin and metformin are effective in preventing adhesions in a rat uterine horn model. A total of 40 non-pregnant, female Wistar albino rats, weighing 180-210 g, were used as a model for post-operative adhesion formation. The rats were randomized into four groups after seven standard lesions were inflicted in each uterine horn and lower abdominal sidewall using bipolar cauterization. The rats were given atorvastatin 2.5 mg/kg/day, p.o. (10 rats), atorvastatin 30 mg/kg/day, p.o. (10 rats), metformin 50 mg/kg/day, p.o. (10 rats) and no treatment was applied in the control group (10 rats). The animals were killed 2 weeks later and adhesions were scored both clinically and pathologically by authors blinded to groups. One rat in the control group died before the end of the 2 week period. Total clinical adhesion scores regarding extent, severity and degree of adhesions and histopathological findings including inflammation and fibrosis were significantly lower in the metformin (P < 0.001 and P < 0.01, respectively) and atorvastatin 30 mg/kg/day (P < 0.001 and P < 0.01, respectively) groups when compared with control group. Metformin and atorvastatin are both effective for prevention of adhesion formation in a rat uterine horn model. PMID:19298747

Yilmaz, Bulent; Aksakal, Orhan; Gungor, Tayfun; Sirvan, Levent; Sut, Necdet; Kelekci, Sefa; Soysal, Sunullah; Mollamahmutoglu, Leyla

2009-03-01

255

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

PubMed Central

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.

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

2014-01-01

256

The alpha1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration.  

PubMed

Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin, an alpha1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus, prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data suggest that the alpha1 adrenergic system may contribute to mechanisms that promote dependence in rats with extended access. PMID:18703080

Greenwell, Thomas N; Walker, Brendan M; Cottone, Pietro; Zorrilla, Eric P; Koob, George F

2009-01-01

257

Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats  

PubMed Central

Background Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke. Methods Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1?, TNF-?, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra. Results 24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1? (79%; p < 0.001), TNF-? (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls. Conclusions Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.

2011-01-01

258

Intrastriatal injection of hypoxanthine reduces striatal serotonin content and impairs spatial memory performance in rats  

Microsoft Academic Search

The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine, a metabolite accumulated\\u000a in Lesch-Nyhan disease, on rats’ performance in the Morris water maze tasks, along with the monoamine content in striatum\\u000a of rats. Male adult Wistar rats were divided in two groups: (1) saline-injected and (2) hypoxanthine-injected group. Seven\\u000a days after solutions infusion, animals

Caren Serra Bavaresco; Fabria Chiarani; Eduardo Duringon; Marcelo Machado Ferro; Cláudio Da Cunha; Carlos Alexandre Netto; Angela Terezinha de Souza Wyse

2007-01-01

259

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

Microsoft Academic Search

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

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

2010-01-01

260

Intravenous cocaine self-administration in rats is reduced by dietary l -tryptophan  

Microsoft Academic Search

Rats were trained to self-administer intravenously-delivered cocaine. Four lever-press responses resulted in a cocaine infusion (0.2 mg\\/kg) during daily 24-h sessions. The rats were also trained to obtain water from tongue-operated solenoid-driven drinking spouts. Ground food and water from a standard drinking bottle were also available. When cocaine injections reached stable levels,l-tryptophan was mixed with the rats' food for 5

Marilyn E. Carroll; Sylvie T. Lac; Marisel Asencio; Rebecca Kragh

1990-01-01

261

Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats  

Microsoft Academic Search

Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl4-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg\\/kg\\/d), or placebo for 2 weeks. Healthy rats, as controls, were treated

Vicente Lorenzo-Zúñiga; Ramón Bartol??; Ramón Planas; Alan F. Hofmann; Belén Viñado; Lee R. Hagey; José M Hernández; Josep Mañé; Marco A. Alvarez; Vicente Ausina; Miquel Angel Gassull

2003-01-01

262

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

PubMed

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

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

2012-05-01

263

Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress  

PubMed Central

Background This study examined the effects of Palm vitamin E (PVE) and ?-tocopherol (?-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO?+?XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Methods Sixty male Sprague–Dawley rats (200-250?g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or ?-TF at 60?mg/kg body weight. After the treatment period of 28?days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO?+?XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and ?-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and ?-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or ?-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

2012-01-01

264

Hippocampal Neuroligin-2 Overexpression Leads to Reduced Aggression and Inhibited Novelty Reactivity in Rats  

PubMed Central

Disturbances of the excitation/inhibition (E/I) balance in the brain were recently suggested as potential factors underlying disorders like autism and schizophrenia resulting in associated behavioral alterations including changes in social and emotional behavior as well as abnormal aggression. Neuronal cell adhesion molecules (nCAMs) and mutations in these genes were found to be strongly implicated in the pathophysiology of these disorders. Neuroligin2 (nlgn2) is a postsynaptic cell adhesion molecule, which is predominantly expressed at inhibitory synapses and required for synapse specification and stabilization. Changes in the expression of nlgn2 were shown to result in alterations of social behavior as well as altered inhibitory synaptic transmission, hence modifying the E/I balance. In our study, we focused on the role of nlgn2 in the dorsal hippocampus in the regulation of emotional and social behaviors. To this purpose, we injected an AAV construct overexpressing nlgn2 in the hippocampus of rats and investigated the effects on behavior and on markers for the E/I ratio. We could show an increase in GAD65, a GABA-synthesizing protein in neuronal terminals, and furthermore, reduced exploration of novel stimuli and less offensive behavior. Our data suggest nlgn2 in the hippocampus to be strongly implicated in maintaining the E/I balance in the brain and thereby modulating social and emotional behavior.

Kohl, Christine; Riccio, Orbicia; Grosse, Jocelyn; Zanoletti, Olivia; Fournier, Celine

2013-01-01

265

Oral administration of Eucalyptus globulus extract reduces the alloxan-induced oxidative stress in rats.  

PubMed

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the putative protective effect of Eucalyptus globulus, a medicinal plant, was investigated in alloxan-diabetic rats. E. globulus extract was given in drinking water for 15 days at a daily dose equivalent to 130 mg dry leaves/kg of body weight. Lipids peroxidation level and activities of catalase, superoxide-dismutase and glutathione peroxidase were then measured in liver and kidney. Under our experimental conditions, eucalyptus extract was found to significantly reduce the blood glucose level in diabetic animals but failed to restore the liver glycogen level, whereas insulin lowered blood glucose and restored liver glycogen to high concentration. Our results suggest that the antihyperglycemic action of eucalyptus extract is not exerted via the stimulation of insulin secretion but rather unveil a proper effect of the extract involving the enhancement of peripheral glucose uptake. In addition, eucalyptus extract appears to exert an antioxidative activity demonstrated (1) by the increase of catalase, superoxide-dismutase and gluthatione-peroxidase activities in liver and kidney, and (2) a lowering of lipids peroxidation level in these organs. In conclusion, the present study indicates that extract of E. globulus, administered per os, could be used with some profit in diabetic patients. PMID:19540215

Ahlem, Soussi; Khaled, Hamden; Wafa, Marouane; Sofiane, Bezzine; Mohamed, Damak; Jean-Claude, Murat; Abdelfattah, El Feki

2009-09-14

266

Reduced anticipatory dopamine responses to food in rats exposed to high fat during early development.  

PubMed

We have previously demonstrated that exposure to high fat (HF) during early development alters the presynaptic regulation of mesolimbic dopamine (DA), and increases incentive motivation for HF food rewards. The goal of the present experiments was to examine the long-term consequences of early exposure to HF on anticipatory and consumatory nucleus accumbens (NAc) DA responses to HF food rewards. Mothers were maintained on a HF (30% fat) or control diet (CD; 5% fat) from gestation day 13 to postnatal day 22 when offspring from both diet groups were weaned and maintained on the CD until adulthood. In vivo NAc DA responses to food anticipation and consumption were measured in a Pavlovian conditioning paradigm using voltammetry in freely moving rats. HF-exposed offspring displayed reduced NAc DA responses to a tone previously paired with the delivery of HF food rewards. In an unconditioned protocol, consumatory NAc DA responses could be isolated, and were similar in HF and control offspring. These data demonstrate that exposure to HF through maternal diet during early development might program behavioral and functional responses associated with mesolimbic DA neurotransmission, thus leading to an increased HF feeding and obesity. PMID:22964789

Naef, L; Moquin, L; Gratton, A; Walker, C-D

2013-06-01

267

Exogenous cholecystokinin-8 reduces vagal efferent nerve activity in rats through CCK(A) receptors.  

PubMed

It has been proposed that the vagus nerve plays a role in mediating cholecystokinin-8 (CCK-8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague-Dawley rats was recorded. Intravenous infusion of CCK-8 (0.1-1 nmol) suppressed the efferent activity. The effect of CCK-8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy. Intravenous infusion of CCK(A) receptor antagonist L-364,718 (1-100x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8, but the CCK(B) receptor antagonist L-365,260 (1-100x10(-6) g) did not in the conditions of either partial or total vagotomy. Intracisternal infusion of L-364,718 (1x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8 i.v. Infusion of exogenous CCK-8 did not affect the activity of supradiaphragmatic vagal afferents. The results suggest that the effect of systemically administered CCK-8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCK(A) receptors. PMID:10780970

Bucinskaite, V; Kurosawa, M; Lundeberg, T

2000-04-01

268

French maritime pine bark extract Pycnogenol reduces thromboxane generation in blood from diabetic male rats.  

PubMed

The protective effect of Pycnogenol against cardiovascular diseases was clearly demonstrated. Nevertheless, little is known about its antithrombotic effect, especially in diabetes associated with enhanced thromboxane synthesis leading to severe vascular complications. Therefore, the main purpose of our study was to evaluate the effect of long-term Pycnogenol intake on synthesis of prothrombotic thromboxane A(2) (TXA(2)) in animal model of insulin-dependent diabetes. The levels of main plasma TXA(2) metabolite, thromboxane B(2) (TXB(2)), were assessed by enzyme-linked immunosorbent assay. Diabetes was induced in Wistar male rats by single injection of streptozotocin, resulting after 8 weeks in significant body weight reduction, increased plasma glucose concentrations, and decreased plasma C-peptide levels, compared to non-diabetic animals. There was no significant reduction of plasma glucose concentrations after Pycnogenol ingestion. It was found, however, that daily administration of either Pycnogenol (5mg/kg b.wt.) or acetylsalicylic acid (ASA, 10mg/kg b.wt.) significantly reduced plasma TXB(2) concentrations, and this inhibitory effect was higher in the latter case. Nonetheless, simultaneous administration of Pycnogenol and ASA did not improve effectiveness of ASA-mediated decrease in TXB(2) generation. The results of the present study suggest that Pycnogenol might have a beneficial antithrombotic effect when administered alone or as a supplementation of standard antiplatelet therapy in diabetic patients. PMID:17698319

Nocun, Marek; Ulicna, Olga; Muchova, Jana; Durackova, Zdenka; Watala, Cezary

2008-03-01

269

Hypertonic saline resuscitation reduces apoptosis of intestinal mucosa in a rat model of hemorrhagic shock  

Microsoft Academic Search

Objective  To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with\\u000a hemorrhagic shock.\\u000a \\u000a \\u000a \\u000a Methods  A model of rat with severe hemorrhagic shock was established in 21 Sprague-Dawley (SD) rats. The rats were randomly divided\\u000a into the sham group, normal saline resuscitation (NS) group, and hypertonic saline resuscitation (HTS) group, with 7 in each

Yuan-qiang Lu; Wei-dong Huang; Xiu-jun Cai; Lin-hui Gu; Han-zhou Mou

2008-01-01

270

Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells  

PubMed Central

Background/aims Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding, and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and resulting downstream toxic effects in cultured T51B rat liver epithelial cells. Methods T51B cells were loaded with ferric ammonium citrate (FAC) with or without the iron delivery agent 8-hydroxyquinoline. Cytotoxicity was measured by MTT assay. Iron uptake and iron bioavailability were documented by chemical assay, quench of calcein fluorescence, and ferritin induction. Reactive oxygen species (ROS) were measured by fluorescence assay using 2?,7?-dichlorodihydrofluorescein diacetate. Oxidative stress signaling to jnk, c-jun, and p38 was measured by western blot with phospho-specific antibodies. Results Curcumin bound iron, but did not block iron uptake or bioavailability in T51B cells given FAC. However, it reduced cytotoxicity, blocked generation of ROS, and eliminated signaling to cellular stress pathways caused by iron. Inhibition was observed over a wide range of FAC concentrations (50 – 500 ?M), with an apparent IC50 in all cases between 5 and 10 ?M curcumin. In contrast, desferoxamine blocked both iron uptake and toxic effects of iron at concentrations that depended on the FAC concentration. Effects of curcumin also differed from those of ?-tocopherol, which did not bind iron and was less effective at blocking iron-stimulated ROS generation. Conclusions Curcumin reduced iron-dependent oxidative stress and iron toxicity in T51B cells without blocking iron uptake.

Messner, Donald J.; Sivam, Gowsala; Kowdley, Kris V.

2008-01-01

271

Reducing effect of matrix metalloproteinase inhibitors on serum triacylglycerol in streptozotocin-induced diabetic rats and Zucker fa/fa rats.  

PubMed

In the course of the investigation of effects of newly synthesized matrix metalloproteinase inhibitors (MMPIs), FYK-1388, FYK-1352 and F61-1008, which have strong and broad matrix metalloproteinase (MMP) inhibitory activity, on wound healing in streptozotocin (STZ)-induced diabetic rats, strong reducing effects on serum triacylglycerol (TG) have been found. Namely, when examined using breaking wound strength as an index, MMPIs did not significantly facilitate wound healing in STZ-induced diabetic rats. Unexpectedly, however, the treatment of STZ-induced diabetic rats with MMPIs markedly lowered the serum level of TG without changing the blood glucose level. Among these compounds tested, FYK-1388 was the most effective, and the compound reduced serum concentrations of TG and cholesterol and levels of very low-density lipoprotein (VLDL)-TG and low density lipoprotein (LDL)-cholesterol in a dose-dependent manner. FYK-1388 did not affect serum levels of free fatty acids, high-density lipoprotein (HDL)-cholesterol, aspartate aminotransferase and alanine aminotransferase, mass of body fat, liver weights, and hepatic contents of TG and cholesterol. Moreover, treatment of Zucker fa/fa rats with FYK-1388 lowered serum levels of TG and cholesterol without changing blood levels of glucose and insulin. Since the structures of these MMPIs markedly differ from those of the hypotriglyceridemic drugs that are used clinically, it seems plausible that these MMPIs could be used as a new type of hypotriglyceridemic drug. PMID:17666804

Morikawa, Tadanori; Toyama, Tomoaki; Kudo, Naomi; Kawashima, Yoichi

2007-08-01

272

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats  

Microsoft Academic Search

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

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

2007-01-01

273

Fibrin glue reduces the severity of intra-abdominal adhesions in a rat model  

Microsoft Academic Search

Background: The purpose of this study was to determine whether fibrin glue inhibits intra-abdominal adhesions.Methods: Twenty rats underwent midline laparotomy. To maximize adhesions, bilateral peritoneal muscular defects were created and covered with polypropylene mesh sewn with a braided suture. The bowel was abraded with dry gauze. Rats were randomized to either fibrin glue (FG) sprayed over the mesh or to

Christian de Virgilio; Magdi Elbassir; Alvaro Hidalgo; Bethann Schaber; Samuel French; Sameer Amin; Bruce E. Stabile

1999-01-01

274

Repeated Restraint Stress Reduces Opioid Receptor Binding in Different Rat CNS Structures  

Microsoft Academic Search

Different effects of exposure to acute or to repeated stress have been observed upon the nociceptive response in rats. In the present study, we repeatedly submitted Wistar rats to restraint for 40 days, a treatment known to induce an increase in the nociceptive response in the tail-flick test. Afterwards, the effect of repeated restraint stress on the density of opioid

Giovana Dantas; Iraci Lucena Da Silva Torres; Leonardo Machado Crema; Diogo R. Lara; Carla Dalmaz

2005-01-01

275

Reduced contraction strength with increased intracellular [Ca2+] in left ventricular trabeculae from failing rat hearts  

PubMed Central

Intracellular calcium ([Ca2+]i) and isometric force were measured in left ventricular (LV) trabeculae from spontaneously hypertensive rats (SHR) with failing hearts and normotensive Wistar-Kyoto (WKY) controls. At a physiological stimulation frequency (5 Hz), and at 37 °C, the peak stress of SHR trabeculae was significantly (P ?; 0.05) reduced compared to WKY (8 ± 1 mN mm?2(n = 8)vs. 21 ± 5 mN mm?2(n = 8), respectively). No differences between strains in either the time-to-peak stress, or the time from peak to 50 % relaxation were detected. Measurements using fura-2 showed that in the SHR both the peak of the Ca2+ transient and the resting [Ca2+]i were increased compared to WKY (peak: 0.69 ± 0.08 vs. 0.51 ± 0.08 ?m (P ? 0.1) and resting: 0.19 ± 0.02 vs. 0.09 ± 0.02 ?m (P ? 0.05), SHR vs. WKY, respectively). The decay of the Ca2+ transient was prolonged in SHR, with time constants of: 0.063 ± 0.002 vs. 0.052 ± 0.003 s (SHR vs. WKY, respectively). Similar results were obtained at 1 Hz stimulation, and for[Ca2+]o between 0.5 and 5 mm. The decay of the caffeine-evoked Ca2+ transient was slower in SHR (9.8 ± 0.7 s (n = 8)vs. 7.7 ± 0.2 s (n = 8) in WKY), but this difference was removed by use of the SL Ca2+-ATPase inhibitor carboxyeosin. Histological examination of transverse sections showed that the fractional content of perimysial collagen was increased in SHR compared to WKY (18.0 ± 4.6 % (n = 10)vs. 2.9 ± 0.9 % (n = 11) SHR vs. WKY, respectively). Our results show that differences in the amplitude and the time course of the Ca2+ transient between SHR and WKY do not explain the reduced contractile performance of SHR myocardium per se. Rather, we suggest that, in this animal model of heart failure, contractile function is compromised by increased collagen, and its three-dimensional organisation, and not by reduced availability of intracellular Ca2+.

Ward, Marie-Louise; Pope, Adele J; Loiselle, Denis S; Cannell, Mark B

2003-01-01

276

Attenuation of iminodipropionitrile induced behavioral syndrome by sodium salicylate in rats.  

PubMed

Iminodipropionitrile (IDPN) produces irreversible behavioral abnormalities characterized by excitation with choreiform and circling movements (ECC) syndrome in rodents. Concomitant exposure to drugs or environmental chemicals has been shown to alter IDPN-induced neurobehavioral toxicity. This investigation was undertaken to study the effect of sodium salicylate (SS) on IDPN-induced behavioral abnormalities in rats. The animals were exposed to IDPN (100 mg/kg ip) daily for 8 days. SS was administered daily 30 min before IDPN in the doses of 50, 100 and 200 mg/kg ip for 12 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex and contact inhibition of the righting reflex. Horizontal and vertical locomotor activities and forelimbs grip strength were also measured. After behavioral studies, the animals were sacrificed, and the cerebrum and temporal bones were collected for glutathione analysis and inner ear histopathology, respectively. The onset of ECC syndrome was observed on Day 9 in the IDPN-alone group with 100% incidence on Day 12. Cotreatment with salicylate dose-dependently delayed the onset time and significantly attenuated the incidence and severity of IDPN-induced neurobehavioral signs. IDPN alone significantly increased horizontal motor activity and reduced vertical motor activity and forelimbs grip strength; these effect were significantly reversed by salicylate treatment. Treatment with salicylate also attenuated IDPN-induced depletion of GSH in the cerebrum, suggesting its free radical scavenging property. PMID:12151040

Tariq, Mohammad; Khan, Haseeb Ahmad; Al Moutaery, Khalaf; Al Deeb, Saleh

2002-10-01

277

Hypothalamic kiss1 mRNA and kisspeptin immunoreactivity are reduced in a rat model of polycystic ovary syndrome (PCOS).  

PubMed

An intact hypothalamic kiss1/kisspeptin/kiss1r complex is a prerequisite for reproductive competence, and kisspeptin treatment could be a practical therapeutic approach to some problems of infertility. One such disorder is polycystic ovarian syndrome (PCOS), a common cause of infertility affecting more than 100 million women. A rodent model of PCOS is the prepubertal female rat treated for a prolonged period with dihydrotestosterone (DHT), which induces many of the metabolic characteristics of the syndrome. We hypothesized that hypothalamic kiss1 mRNA levels, and kisspeptin immunoreactivity (ir), would be abnormal in these rats. Prepubertal female rats were exposed to DHT for 60 days. Rats were killed in two groups: at 26 and 60 days of DHT exposure. Kiss1 mRNA was quantified in hypothalamus, pituitary, ovary and visceral adipose tissue. Separate groups of rats provided brain tissue for immunohistochemical analysis of kisspeptin-ir. At 26 days of DHT exposure, hypothalamic kiss1 mRNA was severely depleted. In contrast DHT had no effect on pituitary kiss1 expression but it significantly increased levels of kiss1 mRNA in fat (+9-fold; p<0.01) and in ovary (+3-fold; p<0.05). At 60days, kiss1 expression had reverted to normal in hypothalamus and ovary but remained elevated in fat (+4-fold; p<0.05). Immunohistochemical analysis revealed that after 26 days of exposure to DHT, kisspeptin-ir was almost completely absent in the arcuate nucleus and a large depletion in kisspeptin +ve fibers was also seen in the paraventricular nucleus, supraoptic nucleus and in the anteroventral periventricular area. At 60 days, despite restored normal levels of kiss1 mRNA, hypothalamic kisspeptin-ir remained depleted in the treated rats. In summary Kiss1 gene expression is differentially affected in various tissues by chronic exposure to dihydrotestosterone in a rat model of polycystic ovary syndrome. In hypothalamus, specifically, kiss1 mRNA, and levels of kisspeptin immunoreactivity, are significantly reduced. Since these rats exhibit many of the characteristics of polycystic ovary syndrome, we suggest that atypical kiss1 expression may contribute to the multiple tissue abnormalities observed in women with this disorder. However, and of some importance, our data do not appear to be consistent with the elevated levels of LH seen in women with PCOS; i.e. reduced levels of hypothalamic kiss1 mRNA and kisspeptin immunoreactivity observed in DHT-treated rats are unlikely to produce elevated LH secretion. PMID:22668987

Brown, Russell E; Wilkinson, Diane A; Imran, Syed A; Caraty, Alain; Wilkinson, Michael

2012-07-27

278

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

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

279

Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats  

PubMed Central

Background Animal studies show that diets containing resistant starch (RS) at levels not achievable in the human diet result in lower body weight and/or adiposity in rodents. We aimed to determine whether RS dose-dependently reduces adiposity in obesity-prone (OP) and obesity-resistant (OR) rats. Methods Male Sprague–Dawley rats (n=120) were fed a moderate-fat, high-energy diet for 4 wk. Rats that gained the most weight (40%) were classified as obesity-prone (OP) and obesity-resistant (OR) rats were the 40% that gained the least weight. OP and OR rats were randomly allocated to one of six groups (n=8 for each phenotype). One group was killed for baseline measurements, the other five groups were allocated to AIN-93 based diets that contained 0, 4, 8, 12 and 16% RS (as high amylose maize starch) for 4 wk. These diets were matched for total carbohydrate content. At 0, 4 and 7 wk from the start of the study insulin sensitivity was calculated by homeostasis model assessment of insulin resistance (HOMA-IR) and adiposity was determined by dual-energy X-ray absorptiometry (DXA). At 8 wk, rats were euthanized and fat pad weights, intestinal digesta short chain fatty acid (SCFA) pools and plasma gut hormone levels were determined. Results Obesity prone rats gained less weight with 4, 12 and 16% RS compared to 0% RS, but the effect in OR animals was significant only at 16% RS. Irrespective of phenotype, diets containing ?8% RS reduced adiposity compared to 0% RS. Energy intake decreased by 9.8 kJ/d for every 4% increase in RS. All diets containing RS increased total SCFA pools in the caecum and lowered plasma GIP concentrations compared to the 0% RS, whereas plasma GLP-1 and PYY were increased when the diet contained at least 8% RS. Insulin sensitivity was not affected by RS. Conclusion RS in amounts that could be potentially consumed by humans were effective in reducing adiposity and weight gain in OP and OR rats, due in part to a reduction in energy intake, and changes in gut hormones and large bowel carbohydrate fermentation.

2012-01-01

280

Treatment with an Antibody to VLA-1 Integrin Reduces Glomerular and Tubulointerstitial Scarring in a Rat Model of Crescentic Glomerulonephritis  

PubMed Central

The ?1?1 integrin (VLA-1) is a major collagen/laminin receptor that regulates fibroblast proliferation and mesangial cell migration and cell contraction. We have examined the effect of an antibody to VLA-1 in crescentic glomerulonephritis. Nephrotoxic nephritis was induced in Wistar-Kyoto rats and rats were given monoclonal antibody to VLA-1 (Ha31/8), 2.5 mg/kg, on alternate days. Antibodies were given from day ?1 to day 10 or from day 14 to day 28. Treatment from day ?1 to day 10, during the early inflammatory phase of nephrotoxic nephritis, had no effect on albuminuria or glomerular crescent formation. In the delayed treatment experiment, all rats developed florid crescentic glomerulonephritis, and control rats showed marked glomerular and tubulointerstitial scarring at day 32. VLA-1 expression, by immunohistochemistry, was increased in glomeruli and around tubules. Proteinuria did not differ between groups. In anti-VLA-1-treated rats, serum creatinine was significantly lower at day 32 (P = 0.002) and renal survival was significantly better (P = 0.045). Both glomerular and interstitial scarring were significantly less at day 32 in rats given anti-VLA-1 (P = 0.002). Deposition of ED(A) fibronectin, a marker of new matrix synthesis, and of type IV collagen, were reduced in glomeruli and interstitium in anti-VLA-1-treated animals (P = 0.0006). Expression of ?-smooth muscle actin, a marker of myofibroblasts, showed no significant difference. Expression of matrix metalloproteinase-9 was increased in the glomeruli of rats treated with anti-VLA-1. We conclude that VLA-1 mediates both glomerular and interstitial fibrosis in crescentic glomerulonephritis and that neutralization of VLA-1, which enhanced expression of matrix metalloproteinase-9, is a possible therapeutic strategy in progressive renal scarring.

Cook, H. Terence; Khan, Sarah B.; Allen, Andrew; Bhangal, Gurjeet; Smith, Jennifer; Lobb, Roy R.; Pusey, Charles D.

2002-01-01

281

(-) Epicatechin prevents alterations in lysosomal glycohydrolases, cathepsins and reduces myocardial infarct size in isoproterenol-induced myocardial infarcted rats.  

PubMed

The preventive effects of (-) epicatechin on oxidative stress, cardiac mitochondrial damage, altered membrane bound adenosine triphosphatases and minerals were reported previously in isoproterenol-induced myocardial infarction model. Leakage of lysosomal glycohydrolases and cathepsins play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the preventive effects of (-) epicatechin on alterations in lysosomal glycohydrolases, cathepsins and myocardial infarct size in isoproterenol-induced myocardial infarcted rats. Male albino Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for a period of 21 days. After the pretreatment period, isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats at an interval of 24h for two days to induce myocardial infarction. The levels of serum cardiac troponin-I and the activities of serum and heart lysosomal enzymes (?-glucuronidase, ?-N-acetyl glucosaminidase, ?-galactosidase, cathepsin-B and cathepsin-D) were increased significantly (P<0.05) and the activities of ?-glucuronidase and cathepsin-D in the heart lysosomal fractions were significantly (P<0.05) decreased in isoproterenol-induced myocardial infarcted rats. The in vitro study revealed the potent antioxidant action of (-) epicatechin. Pretreatment with (-) epicatechin daily for a period of 21 days prevented the leakage of cardiac marker, lysosomal glycohydrolases, cathepsins, and reduced infarct size, thereby protecting the lysosomal membranes in isoproterenol-induced myocardial infarcted rats, by virtue of its membrane stabilizing property. PMID:23454557

Prince, Ponnian Stanely Mainzen

2013-04-15

282

l-Cysteine reduces oral ethanol self-administration and reinstatement of ethanol-drinking behavior in rats.  

PubMed

Our previous findings have shown that l-cysteine, a non essential amino acid, prevented ethanol (EtOH) induced conditioned place preference. The aim of the present study was to examine the effect of l-cysteine on the acquisition and maintenance of oral EtOH self-administration and on the reinstatement of EtOH-drinking behavior in Wistar rats. Rats were pretreated intraperitoneally with saline or l-cysteine (20 and 40 mg/kg) 30 min before each acquisition trial, in an operant nose-poking paradigm where they were given the opportunity to orally self-administer tap water or EtOH (5-10% v/v). Further, to evaluate if l-cysteine reduces the acquired oral EtOH self-administration, we carried out an independent experiment in which rats were trained to self-administer EtOH (10%); after all groups of rats developed similarly stable oral EtOH self-administration, the effect of l-cysteine (0, 40, 60, 80 and 100mg/kg) was tested. An additional group of rats was pretreated with saline or l-cysteine (80 mg/kg) and tested on reinstatement after EtOH extinction and, at the end of last reinstatement session, were utilized to measure blood and brain EtOH levels. The animals that had access to EtOH solution discriminated between the active and inactive nose-pokes and showed rates of active nose-pokes significantly higher than the tap water group. Furthermore, rats self-administering EtOH (10%) also demonstrated extinction behavior and gradually reinstated active nose-poke responding when EtOH was reintroduced. l-cysteine reduced both the acquisition and maintenance of oral EtOH self-administration. The reduced reinstatement of EtOH-drinking behavior was paralleled by a significant reduction of EtOH intake and correlated with blood and brain EtOH levels. The efficacy of l-cysteine on the various phases of alcohol drinking in rats, could represent an interesting pharmacological approach and could open a new line of research for the development of therapies to reduce EtOH intake in alcoholic patients. PMID:19879891

Peana, Alessandra T; Muggironi, Giulia; Calvisi, Giovanna; Enrico, Paolo; Mereu, Maddalena; Nieddu, Maria; Boatto, Gianpiero; Diana, Marco

2010-01-01

283

Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rats.  

PubMed

Rats predisposed to develop diet-induced obesity (DIO) preferentially activate their sympathetic nervous system during intracarotid glucose infusion [B.E. Levin, Intracarotid glucose-induced norepinephrine response and the development of diet-induced obesity, Int. J. Obesity 16 (1992) 451-457.] but their brains are generally less responsive to glucose than diet-resistant rats (DR) [B.E. Levin, K.L. Brown, A.A. Dunn-Meynell, Differential effects of diet and obesity on high and low affinity sulfonylurea binding sites in the rat brain, Brain Res. 739 (1996) 293-300.; B.E. Levin, B. Planas, Defective glucoregulation of brain alpha2-adrenoceptors in obesity-prone rats, Am. J. Physiol. 264 (1993) R305-R311.; B.E. Levin, A.C. Sullivan, Glucose-induced norepinephrine levels and obesity resistance, Am. J. Physiol. 253 (1987) R475-R481.; B.E. Levin, A.C. Sullivan, Glucose-induced sympathetic activation in obesity-prone and resistant rats, Int. J. Obesity 13 (1989) 235-246.]. Here, 1 h intracarotid glucose infusions (4 mg/kg/min) selectively increased Fos-like immunoreactivity (FLIR) in the hypothalamic paraventricular, ventromedial, dorsomedial and arcuate nuclei of inbred DR but not DIO rats. This suggests that enhanced glucose-induced sympathetic activation in DIO rats is related to a failure of glucose to produce neuronal activation in these areas. PMID:9767180

Levin, B E; Govek, E K; Dunn-Meynell, A A

1998-10-19

284

Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.  

PubMed

Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200?mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75?mg/kg and 150?mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25?±?0.24?mg/L h to 7.62?±?0.15?mg/L h and 4.97?±?0.21?mg/L h, and the C(max) value was decreased from 1.31?±?0.03?mg/L to 0.62?±?0.05?mg/L and 0.36?±?0.04?mg/L in rats pretreated with ursodeoxycholic acid at doses of 75?mg/kg and 150?mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. PMID:24135887

Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

2013-11-01

285

Activation of alpha(2)-adrenoceptors in the lateral hypothalamus reduces pilocarpine-induced salivation in rats.  

PubMed

Anti-hypertensive drugs that act on central alpha(2)-adrenoceptors and imidazoline receptors usually cause dry mouth in patients. A central area important for the control of salivary secretion and also for the effects of alpha(2)-adrenoceptor activation is the lateral hypothalamus (LH). Therefore, in the present study we investigated the effects of the injections of moxonidine (an alpha(2)-adrenoceptor and imidazoline agonist) alone or combined with RX 821002 (alpha(2)-adrenoceptor antagonist) into the LH on the salivation induced by intraperitoneal (i.p.) pilocarpine (cholinergic muscarinic agonist). Male Holtzman rats with stainless steel cannula implanted into the LH were used. Saliva was collected using pre-weighted small cotton balls inserted into the animal's mouth under ketamine anesthesia. Salivation induced by i.p. pilorcarpine (4micromol/kg of body weight) was reduced by the injection of moxonidine (10 and 20nmol/0.5microl) into the LH (222+/-46 and 183+/-19mg/7min, vs. vehicle: 480+/-30mg/7min). The inhibitory effect of moxonidine on pilocarpine-induced salivation was abolished by prior injections of RX 821002 (160 and 320nmol/0.5microl) into the LH (357+/-25 and 446+/-38mg/7min). Injections of the alpha(1)-adrenoceptor antagonist prazosin (320nmol/0.5microl) into the LH did not change the effects of moxonidine. The results show that activation of alpha(2)-adrenoceptors in the LH inhibits pilocarpine-induced salivation, suggesting that LH is one of the possible central sites involved in the anti-salivatory effects produced by the treatment with alpha(2)-adrenoceptor agonists. PMID:19041371

Takakura, Ana C; Moreira, Thiago S; Colombari, Débora S A; De Luca, Laurival A; Menani, José V

2009-02-01

286

Fenugreek seeds reduce aluminum toxicity associated with renal failure in rats.  

PubMed

Despite the reports on safety concerns regarding the relationship between aluminum salts and neurological and bone disease, many countries continue to use aluminum as phosphate binders among patients with renal failure. In search for a diet supplement that could reduce aluminum toxicity related to renal failure, we carried out this prospective animal study in which the fenugreek seeds were assessed for their effects on rats nephrotoxicity induced by aluminum chloride (AlCl3). Oral AlCl3 administration during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) led to plasma biochemical changes, an inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status (TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in addition to kidney atrophy and morphological alterations at the level of Bowman's capsule, the glomerulus and different sorts of tubules, reminiscent of some known kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in the diet) during the last 2 months showed its effectiveness in restoring normal plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the TAS, inhibiting LPO and alleviating histopathological changes in the injured kidneys. This study highlights the induced nephrotoxicicity, as well as the related toxicity in the brain and bone, by chronic oral ingestion of the aluminum salts. However, the maintenance of a diet supplemented with fenugreek seeds could offer protection for the kidney, bone and brain, at the same time. PMID:24353832

Belaïd-Nouira, Yosra; Bakhta, Hayfa; Haouas, Zohra; Flehi-Slim, Imen; Ben Cheikh, Hassen

2013-12-01

287

Removal of half the sympathetic innervation does not reduce vasoconstrictor responses in rat tail artery  

PubMed Central

Following reinnervation of denervated rat tail arteries, nerve-evoked contractions are at least as large as those evoked in normally innervated arteries despite a much lower nerve terminal density. Here nerve-evoked contractions have been investigated after transection of half the sympathetic innervation of normal tail arteries. After 1 week, the noradrenergic plexus 50–70 mm along the tail was about half as dense as control. Excitatory junction potentials recorded in smooth muscle cells of arterial segments isolated in vitro were half their normal amplitude. Surprisingly, nerve-evoked contractions of isometrically mounted segments were not reduced in amplitude, as was also the case after only 3 days. After 1 week, enhancement of nerve-evoked contractions by blocking either neuronal re-uptake of noradrenaline with desmethylimipramine or prejunctional ?2-adrenoceptors with idazoxan was similar to control, suggesting that these mechanisms are matched to the number of innervating axons. The relative contribution of postjunctional ?2-adrenoceptors to contractions evoked by long trains of stimuli was enhanced but that of ?1-adrenoceptors was unchanged. Transiently, sensitivity to the ?1-adrenoceptor agonist phenylephrine was slightly increased. After 7 weeks, amplitudes of nerve-evoked contractions remained similar to control, and sensitivity to phenylephrine had recovered but that to the ?2-adrenoceptor agonist clonidine was slightly raised. The normal amplitude of nerve-evoked contractions after partial denervation is only partly explained by the greater contribution of ?2-adrenoceptors. While the post-receptor mechanisms activated by nerve-released transmitter may be modified to amplify the contractions after partial denervation, our findings suggest that these mechanisms are normally saturated, at least in this artery.

Tripovic, Diana; McLachlan, Elspeth M; Brock, James A

2013-01-01

288

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

PubMed

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 (3mg/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 (20mg/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. PMID:16307977

Pinho, Ricardo A; Silveira, Paulo C L; Silva, Luciano A; Luiz Streck, Emílio; Dal-Pizzol, Felipe; F Moreira, José C

2005-11-01

289

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

PubMed

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 immuno-cyto-chemistry. 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

Qi, Chen; Xu, Mingxin; Gan, Jing; Yang, Xinxin; Wu, Na; Song, Lu; Yuan, Weien; Liu, Zhenguo

2014-08-01

290

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

PubMed Central

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.

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

2014-01-01

291

Getting a grip on the evolution of grasping in musteloid carnivorans: a three-dimensional analysis of forelimb shape.  

PubMed

The ability to grasp and manipulate is often considered a hallmark of hominins and associated with the evolution of their bipedal locomotion and tool use. Yet, many other mammals use their forelimbs to grasp and manipulate objects. Previous investigations have suggested that grasping may be derived from digging behaviour, arboreal locomotion or hunting behaviour. Here, we test the arboreal origin of grasping and investigate whether an arboreal lifestyle could confer a greater grasping ability in musteloid carnivorans. Moreover, we investigate the morphological adaptations related to grasping and the differences between arboreal species with different grasping abilities. We predict that if grasping is derived from an arboreal lifestyle, then the anatomical specializations of the forelimb for arboreality must be similar to those involved in grasping. We further predict that arboreal species with a well-developed manipulation ability will have articulations that facilitate radio-ulnar rotation. We use ancestral character state reconstructions of lifestyle and grasping ability to understand the evolution of both traits. Finally, we use a surface sliding semi-landmark approach capable of quantifying the articulations in their full complexity. Our results largely confirm our predictions, demonstrating that musteloids with greater grasping skills differ markedly from others in the shape of their forelimb bones. These analyses further suggest that the evolution of an arboreal lifestyle likely preceded the development of enhanced grasping ability. PMID:23662594

Fabre, A-C; Cornette, R; Slater, G; Argot, C; Peigné, S; Goswami, A; Pouydebat, E

2013-07-01

292

Cloricromene, a coumarine derivative, reduced the development of periodontitis in rats  

Microsoft Academic Search

Recent studies have demonstrated that cloricromene, a coumarin derivative, exerts protective effects in models of inflammation\\u000a and shock. Tumour necrosis factor plays a pivotal role in the induction of genes involved in physiological processes, as well\\u000a as in the response to inflammation. We investigated the effect of cloricromene in a rat model of periodontitis. Periodontitis\\u000a was induced in rats by

Carmelo Muià; Emanuela Mazzon; Daniele Zito; Daniele Maiere; Domenico Britti; Concetta Crisafulli; Giacomo Oteri; Giancarlo Cordasco; Salvatore Cuzzocrea

2006-01-01

293

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

Microsoft Academic Search

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

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

1992-01-01

294

M100240, a dual ACE\\/NEP inhibitor, reduces blood pressure in spontaneously hypertensive rats  

Microsoft Academic Search

Blockade of the renin-angiotensin-aldosterone system may be beneficial in the management of hypertension. Consequently, several dual ACE\\/NEP inhibitors, such as M100240, are in development for the treatment of this condition. The effects of M100240 on blood pressure and heart rate in spontaneously hypertensive rats were evaluated. The study group comprised 5 male rats (Okamoto strain, 14-15 weeks old). Each animal

Daniela Leitzbach; Andreas E. Busch; Wolfgang Linz

2002-01-01

295

Prebiotic and Synbiotic Fructooligosaccharide Administration Fails to Reduce the Severity of Experimental Colitis in Rats  

Microsoft Academic Search

Opposing effects of the prebiotic, fructooligosaccharide, have been reported in experimental colitis. We compared the effects\\u000a of the prebiotic, fructooligosaccharide, alone and in synbiotic combination with Lactobacillus fermentum BR11, on the development of dextran sulfate sodium-induced colitis in rats. Rats consumed an 18 percent casein-based diet\\u000a or diet supplemented with 6 percent fructooligosaccharide or maltodextrin for 14 days. The synbiotic group

Mark S. Geier; Ross N. Butler; Philip M. Giffard; Gordon S. Howarth

2007-01-01

296

? 1 -tetrahydrocannabinol but not cannabidiol reduces contact and aggressive behavior of rats tested in dyadic encounters  

Microsoft Academic Search

A low and a high dose of ?1-Tetrahydrocannabinol (?1-THC) and of cannabidiol (CBD) were IP injected in rats that had been isolated for 7 days. Forty-five minutes after injection, the rats were tested for social interactions with non-isolated, untreated test partners in dyadic encounters under standardized conditions. Different aspects of social behavior were analyzed. The high dose of ?1-THC (10

Jan M. van Ree; Raymond J. M. Niesink; Isaac Nir

1984-01-01

297

Neutrophil elastase inhibitor reduces neutrophil chemoattractant production after ischemia-reperfusion in rat liver  

Microsoft Academic Search

BACKGROUND & AIMS: Neutrophils are important in the development of tissue injury induced by ischemia-reperfusion. The ability of an inhibitor of neutrophil elastase (ONO-5046) to protect against ischemia- reperfusion injury in rat liver was investigated by measuring serum concentrations of cytokine-induced neutrophil chemoattractant.METHODS: Liver ischemia was induced in rats by occluding the portal vein for 30 minutes, and ONO-5046 or

Y Yamaguchi; E Akizuki; O Ichiguchi; F Matsumura; M Goto; N Miyanari; K Mori; S Yamada; M Ogawa

1997-01-01

298

Chronic oral administration of synthetic trypsin inhibitor camostate reduces amylase release from isolated rat pancreatic acini  

Microsoft Academic Search

Summary  In the present study, we examined stimulus-secretion coupling in pancreatic acini prepared from rats given synthetic protease\\u000a inhibitor camostate at a dose of 200 mg\\/kg body wt by an orogastric tube once a day for 10 d. Camostate treatment significantly\\u000a increased pancreatic weight, protein, DNA, and enzyme contents. In acini prepared from the camostate-treated rats, responsiveness\\u000a to both CCK-8 and

Makoto Otsuki; Masatoshi Fujii; Takahiko Nakamura; Satoshi Tani; Yoshinori Okabayashi

1995-01-01

299

Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures  

Microsoft Academic Search

A variety of neurotransmitter receptor changes occur after a course of electroconvulsive seizures (ECS) in rats, including an increased density of adenosine A1 sites. Adenosine antagonism has been related to the proconvulsant action of methylxanthines such as caffeine. We determined tonic-clonic seizure duration in rats given ECS with caffeine (0–175 mg\\/kg, IP) after a course of one or six daily

A. Francis; L. Fochtmann

1995-01-01

300

Stimulation of the occipital or retrosplenial cortex reduces incision pain in rats  

Microsoft Academic Search

The electrical stimulation of the occipital (OC) or retrosplenial (RSC) cortex produces antinociception in the rat tail-flick and formalin tests. This study examined the antinociceptive effects of stimulating the OC or RSC in a rat model of post-incision pain. The involvement of the anterior pretectal nucleus (APtN) as intermediary for the effect of OC or RSC stimulation was also evaluated

Ana Carolina Rossaneis; Gláucia Melo Reis; Wiliam A. Prado

2011-01-01

301

Dietary Conjugated Linoleic Acid Reduces Rat Adipose Tissue Cell Size Rather than Cell Number1  

Microsoft Academic Search

We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g\\/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine

Michael J. Azain; Dorothy B. Hausman; Matthew B. Sisk; William P. Flatt; Dennis E. Jewell

302

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum  

Microsoft Academic Search

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative\\u000a diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the\\u000a cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine,\\u000a and betaine plus ethanol) with different dietary regimens

Masoud Alirezaei; Gholamali Jelodar; Parvin Niknam; Zeynab Ghayemi; Saeed Nazifi

303

Reduced activity of hippocampal group-I metabotropic glutamate receptors in learning-prone rats  

Microsoft Academic Search

Following the hypothesis of the “signal-to-noise” ratio (Riedel, 1996) we examined whether changes in the activity of group-I metabotropic glutamate (mGlu) receptors in the hippocampus are associated with a condition that specifically enhances the learning capacity in rats. As a model, we used rats that had been nursed by mothers drinking a solution of corticosterone (13.5 mg of daily intake

C Cinque; A. R Zuena; P Casolini; R. T Ngomba; D Melchiorri; S Maccari; F Nicoletti; V Di Giorgi Gerevini; A Catalani

2003-01-01

304

Atorvastatin reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation  

Microsoft Academic Search

The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study\\u000a the biochemical and histopathological changes in experimental ischemia and ischemia\\/reperfusion (I\\/R) injury in rat ovaries.\\u000a The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group\\u000a II, a sham

Elif Cadirci; Akgun Oral; Fehmi Odabasoglu; Cenk Kilic; Kagan Coskun; Zekai Halici; Halis Suleyman; Osman Nuri Keles; Bunyami Unal

2010-01-01

305

Vitamin E attenuates cold-induced rat liver oxidative damage reducing H 2O 2 mitochondrial release  

Microsoft Academic Search

Vitamin E is a major chain-breaking antioxidant which is able to reduce liver oxidative damage without modifying aerobic capacity in T3-treated rats. We investigated whether vitamin E has similar effects in hyperthyroid state induced by cold exposure. Cold exposure increased aerobic capacity and O2 consumption in homogenates and mitochondria and tissue mitochondrial protein content. Vitamin E did not modify aerobic

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

2007-01-01

306

Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model  

Microsoft Academic Search

Background: Ischemia-reperfusion injury involves free radical generation and polymorphonuclear neutrophil chemotaxis. Trimetazidine is an anti-ischemic drug that restores the ability of the ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. We evaluated the effect of trimetazidine against ischemia-reperfusion injury after lung transplantation. Methods: Rat single lung transplantation was performed in 3 experimental groups (n =

Ilhan Inci; André Dutly; Valentin Rousson; Annette Boehler; Walter Weder

2001-01-01

307

Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury  

Microsoft Academic Search

Pharmacological modulation of heme oxygenase (HO) gene expression may have significant therapeutic potential in oxidant-induced\\u000a disorders, such as ischemia reperfusion (I\\/R) injury. Higenamine is known to reduce ischemic damages by unknown mechanism(s).\\u000a The protective effect of higenamine on myocardial I\\/R-induced injury was investigated. Ligation of rat left anterior descending\\u000a coronary artery for 30 min under anesthesia was done and followed by

Young Soo Lee; Young Jin Kang; Hye Jung Kim; Min Kyu Park; Han Geuk Seo; Jae Heun Lee; Hye Sook Yun-Choi; Ki Churl Chang

2006-01-01

308

Acetate supplementation reduces microglia activation and brain interleukin-1? levels in a rat model of Lyme neuroborreliosis  

PubMed Central

Background We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. Methods In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16). Acetate supplementation was induced using glyceryl triacetate (6g/kg) by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1?. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. Results We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1? by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. Conclusions These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.

2012-01-01

309

Lovastatin reduces glomerular macrophage influx and expression of monocyte chemoattractant protein-1 mRNA in nephrotic rats  

Microsoft Academic Search

Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and subsequent glomerular macrophage infiltration may play an important role in the development of glomerulosclerosis. Previous studies have shown that lovastatin ameliorates experimental renal disease and reduces MCP-1 expression in serum-stimulated, cultured mesangial cells. We investigated the effects of lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats with puromycin aminonucleoside (PA)

C Guijarro; Y Kim; ZA Massy; BL Kasiske; WF Keane; MP O'Donnell

1998-01-01

310

Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum.  

PubMed

The lateral septum (LS) is a brain nucleus implicated in the addictive process. This study investigated whether withdrawal from chronic amphetamine (AMPH) induces alterations in dopamine (DA) transmission within the LS. Male Sprague-Dawley rats were injected with AMPH (2.5 mg/kg i.p.) or saline during 14 days and thereafter subjected to 24 hr or 14 days of withdrawal. After these withdrawal periods, we measured DA extracellular levels by in vivo microdialysis, DA tissue levels, and tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT2) expression in the LS. Our results showed a significant decrease in K(+) -induced release of DA in the LS of AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. There were no significant differences in DA tissue content and TH expression. Interestingly, there was a decrease of LS VMAT2 expression in AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. This is the first neurochemical evidence showing that withdrawal from repeated AMPH administration decreases K(+) -induced DA release in the rat LS. Our results suggest that this decrease in DA releasability could be due to a decrease in DA vesicular uptake. The possibility that these neurochemical changes are associated with AMPH abstinence syndrome should be further explored. © 2014 Wiley Periodicals, Inc. PMID:24753218

Renard, Georgina M; Sotomayor-Zarate, Ramón; Blanco, Elías H; Gysling, Katia

2014-07-01

311

Functional adaptations in the forelimb muscles of non-human great apes.  

PubMed

The maximum capability of a muscle can be estimated from simple measurements of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area. While the hindlimb anatomy of the non-human apes has been studied in some detail, a comparative study of the forelimb architecture across a number of species has never been undertaken. Here we present data from chimpanzees, bonobos, gorillas and an orangutan to ascertain if, and where, there are functional differences relating to their different locomotor repertoires and habitat usage. We employed a combination of analyses including allometric scaling and ancovas to explore the data, as the sample size was relatively small and heterogeneous (specimens of different sizes, ages and sex). Overall, subject to possible unidentified, confounding factors such as age effects, it appears that the non-human great apes in this sample (the largest assembled to date) do not vary greatly across different muscle architecture parameters, even though they perform different locomotor behaviours at different frequencies. Therefore, it currently appears that the time spent performing a particular behaviour does not necessarily impose a dominating selective influence on the soft-tissue portion of the musculoskeletal system; rather, the overall consistency of muscle architectural properties both between and within the Asian and African apes strengthens the case for the hypothesis of a possible ancient shared evolutionary origin for orthogrady under compressive and/or suspensory loading in the great apes. PMID:22034995

Myatt, Julia P; Crompton, Robin H; Payne-Davis, Rachel C; Vereecke, Evie E; Isler, Karin; Savage, Russell; D'Août, Kristiaan; Günther, Michael M; Thorpe, Susannah K S

2012-01-01

312

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

PubMed Central

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.

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

2013-01-01

313

Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats.  

PubMed

The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16?EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015?EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. PMID:24967382

Rodes, Laetitia; Saha, Shyamali; Tomaro-Duchesneau, Catherine; Prakash, Satya

2014-01-01

314

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

SciTech Connect

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.

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

315

Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats  

PubMed Central

The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16?EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015?EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases.

Saha, Shyamali; Prakash, Satya

2014-01-01

316

Combined effects of quercetin and atenolol in reducing isoproterenol-induced cardiotoxicity in rats: possible mediation through scavenging free radicals.  

PubMed

In this investigation, combined effects of quercetin and atenolol in the regulation of isoproterenol (ISO)-induced cardiotoxicity have been evaluated in rats. While ISO administration increased the levels of serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and glutamate pyruvate transaminase (SGPT) as well as cardiac malondialdehyde (MDA); it reduced the activities of superoxide dismutase, catalase, glutathione peroxidase and the level of reduced glutathione. ISO-induced rats also exhibited ST-segment elevation and tachycardia. Oral administration of atenolol (6 mg/kg) and quercetin (5 mg/kg), along with ISO (5 mg/kg, subcutaneously) every day for 10 days markedly reduced the serum CK-MB, LDH and SGPT levels. Concomitantly the test drugs improved the status of antioxidative enzymes, decreased the cardiac MDA and nearly normalized the electrocardiogram. Electron paramagnetic resonance study also revealed a decrease in 5,5'-dimethyl-1-pyroline-N-oxide-hydroxyl radicals signal intensity when atenolol and quercetin were administered together to ISO-treated rats. In conclusion, the combined treatment of atenolol and quercetin appears to produce a better cardioprotective effect in ISO-induced animals as compared to their individual treatments, and possibly the beneficial actions are associated with the free radical scavenging action of quercetin. PMID:22391854

Panda, Sunanda; Kar, Anand; Banerjee, Tushar; Sharma, Neha

2012-09-01

317

Analysis and Design of Reduced-Size Marchand Rat-Race Hybrid for Millimeter-Wave Compact Balanced Mixers in 130-nm CMOS Process  

Microsoft Academic Search

The analysis and design flow for reduced-size Marchand rat-race hybrids are presented in this paper. A simplified single-to-differential mode is used to analyze the Marchand balun, and the methodology to reduce the size of Marchand balun is developed. The 60-GHz CMOS singly balanced gate mixer and diode mixer using the reduced-size Marchand rat-race hybrid are implemented to verify the design

Chun-Hsien Lien; Chi-Hsueh Wang; Chin-Shen Lin; Pei-Si Wu; Kun-You Lin; Huei Wang

2009-01-01

318

Spinal subarachnoid adrenal medullary transplants reduce hind paw swelling and peripheral nerve transport following formalin injection in rats  

PubMed Central

Previous studies have demonstrated that adrenal medullary chromaffin cells transplanted into the spinal subarachnoid space significantly reduced pain-related behavior following hind paw plantar formalin injection in rats. The data suggests a centrally mediated antinociceptive mechanism. The spinal transplants may have effects on sciatic nerve function as well. To address this, the current study examined the effects of spinal adrenal transplants on hind paw edema and the anterograde transport of substance P (SP) that occur following formalin injection. Robust formalin-evoked edema, as well as hind paw flinching, was observed in striated muscle control-transplanted rats, which were not observed in adrenal-transplanted rats. To visualize transport of SP, the sciatic nerve was ligated ipsilateral to formalin injection and the nerve was processed 48 h later for immunocytochemistry. A significant formalin-induced accumulation of SP immunoreactivity (IR) was observed proximal to the ligation in control-transplanted rats. In contrast, there was significantly less SP IR observed from nerve of adrenal-transplanted rats, suggesting a diminution of anterograde axoplasmic transport by adrenal transplants. The change in SP IR may have been due to an alteration of transport due to formalin injection, thus, transport was visualized by the accumulation of growth-associated protein 43 (GAP43) at the ligation site. Formalin injection did not significantly increase proximal accumulation of GAP43 IR, indicating that formalin does not increase anterograde transport. Surprisingly, however, adrenal transplants significantly diminished GAP43 IR accumulation compared to control-transplanted rats. These data demonstrate that spinal adrenal transplants can attenuate the formalin-evoked response by modulating primary afferent responses.

Herzberg, Uri; Hama, Aldric; Sagen, Jacqueline

2009-01-01

319

Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene reduces acute hypoxic pulmonary vasoconstriction in rats.  

PubMed Central

Nitric oxide (NO), a vasodilator involved in the regulation of pulmonary vascular tone, is synthesized by a family of enzymes, nitric oxide synthases (NOS). To investigate whether adenoviral-mediated overexpression of constitutive endothelial NOS (ceNOS) would attenuate hypoxic pulmonary vasoconstriction, we aerosolized 3 X 10(9) plaque forming units of a recombinant adenovirus containing the ceNOS gene (AdCMVceNOS) into rat lungs. Four days after infection, transgene expression was confirmed using immunoblot techniques. Diffuse ceNOS immunostaining was detected in alveoli and medium-sized and small pulmonary vessels of AdCMVceNOS-transduced lungs. AdCMVceNOS-transduction was associated with an 86% increase in [3H]arginine to [3H]citrulline conversion and a rise in pulmonary cGMP levels from 7 +/- 1 to 59 +/- 9 pmol/mg protein in lungs from AdCMVceNOS versus control rats, (P < 0.05). During acute hypoxia (FIO2 = 0.10) for 25 min, mean pulmonary artery pressure (PAP) increased significantly from 17 +/- 1 to 27 +/- 1 mmHg in rats aerosolized with saline (n = 4) and from 18 +/- 1 to 28 +/- 1 mmHg in rats given an adenoviral vector expressing a nuclear-targeted beta-galactosidase gene (AdCMV beta gal, n = 8). In contrast, in AdCMVceNOS-transduced rats (n = 8) the hypoxia-induced increase in PAP was significantly attenuated (18 +/- 1 to 23 +/- 2 mmHg). Systemic blood pressure was not affected by aerosol gene transfer. Thus, adenoviral-mediated ceNOS gene transfer to rat lungs increases ceNOS expression and activity, and reduces acute hypoxic pulmonary vasoconstriction. Aerosolized recombinant adenovirus overexpressing vasodilatory proteins can act as a selective pulmonary vasodilator and may hold promise as a future therapeutic strategy for pulmonary hypertension.

Janssens, S P; Bloch, K D; Nong, Z; Gerard, R D; Zoldhelyi, P; Collen, D

1996-01-01

320

Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.  

PubMed

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4 weeks later when the tumor represented 1-2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia. PMID:21334429

Pourtau, Line; Leemburg, Susan; Roux, Pascale; Leste-Lasserre, Thierry; Costaglioli, Patricia; Garbay, Bertrand; Drutel, Guillaume; Konsman, Jan Pieter

2011-05-01

321

Vitamin E Gamma-tocopherol Reduces Airway Neutrophil Recruitment after Inhaled Endotoxin Challenge in Rats and in Healthy Volunteers  

PubMed Central

Rationale Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (gamma tocopherol, ?T) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether ?T supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. Methods F344/N rats were randomized to oral gavage with ?T versus placebo, followed by intranasal LPS (20 ug) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo controlled crossover study where they consumed either a ?T-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 hours after inhaled LPS. The effect of ?T compared to placebo on airway neutrophils post-LPS was compared using a repeated measures analysis of variance. Results In rats, oral ?T supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, ?T treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Conclusion Oral supplementation with ?T reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that ?T is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations.

Hernandez, Michelle L; Wagner, James G.; Kala, Aline; Mills, Katherine; Wells, Heather B; Alexis, Neil E; Lay, John C; Jiang, Qing; Zhang, Hongtao; Zhou, Haibo; Peden, David B

2013-01-01

322

Inactivation of neuronal function in the amygdaloid region reduces tail artery blood flow alerting responses in conscious rats.  

PubMed

Few studies have investigated whether neuronal function in the amygdaloid complex is necessary for the occurrence of the cardiovascular response to natural (unconditioned) environmental threats. In the present investigation in conscious unrestrained Sprague-Dawley rats we inactivated neuronal function in the amygdaloid complex acutely (bilateral muscimol injections) or chronically (unilateral or bilateral ibotenic acid injections) and measured the effect on sudden falls in tail artery blood flow elicited by non-noxious salient stimuli (sympathetic cutaneous vasomotor alerting responses, SCVARs). After acute bilateral injection of vehicle (200nl Ringer's solution) the SCVAR index was 81 ± 2%, indicating that tail blood flow was reduced by 81% in response to the salient stimuli. After acute bilateral injection of muscimol (1 nmol in 200 nl of Ringer's solution) into the amygdaloid complex the SCVAR index was 49 ± 5%, indicating that tail blood flow was reduced by 49% in response to the salient stimuli (p<0.01 versus vehicle, n=7 rats for vehicle and 6 for muscimol). One week after unilateral ibotenic acid lesions, the SCVAR index was 68 ± 3%, significantly less than 90 ± 1%, the corresponding value after unilateral injection of vehicle (p<0.01, n=6 rats in each group). After bilateral ibotenic acid lesions the SCVAR index was 52 ± 4%, significantly less than 93 ± 1%, the corresponding value after bilateral injection of vehicle (p<0.001, n=6 rats in each group). Ibotenic acid caused extensive neuronal destruction of the whole amygdaloid complex, as well as lateral temporal lobe structures including the piriform cortex. Our results demonstrate that the amygdaloid complex plays an important role in mediating the tail artery vasoconstriction that occurs in rats in response to the animal's perception of a salient stimulus, redirecting blood to areas of the body with more immediate metabolic requirements. PMID:23069750

Mohammed, M; Kulasekara, K; De Menezes, R C; Ootsuka, Y; Blessing, W W

2013-01-01

323

Glucose treatment reduces memory deficits in young adult rats fed high-fat diets.  

PubMed

Feeding rats high-fat diets for 3 months produces a widespread cognitive deficit that affects performance on a wide range of learning and memory tasks. The present study tested the hypothesis that this effect is related to a fat-induced impairment in glucose metabolism. Following 3 months of dietary intervention (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow), male Long-Evans rats were tested on a variable interval delayed alternation (VIDA) task that measures learning and memory functions that differentially involve specific brain regions. Relative to rats fed chow, rats consuming the high-fat diets were impaired on all aspects of VIDA performance. Following baseline testing, rats were maintained on their respective diets and the effect of glucose administration (100 mg/kg BW; i.p.) was examined. For the next 6 days, animals alternately received injections of saline or glucose 30 min prior to VIDA testing. Glucose treatment improved performance, with the effect being most pronounced at the longer intertrial intervals where task performance is sensitive to hippocampal impairment. Importantly, the beneficial effect of glucose were confined to those animals consuming the high-fat diets and were not observed in rats fed chow. These results demonstrate that glucose administration can overcome those deficits associated with hippocampal function in rats fed high-fat diets and are consistent with the hypothesis that high-fat diets, in part, mediate their effect through the development of insulin resistance and glucose intolerance. PMID:11222059

Greenwood, C E; Winocur, G

2001-03-01

324

Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart  

PubMed Central

Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. The effect of interferon-induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg?1, p.o.) and nifedipine (0.1 mg kg?1, i.v.) was studied in Sprague–Dawley rats. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation. Maximum binding of 3H-nitrendipine to cardiac cell membrane was significantly reduced from 63.2±2.5 fmol mg?1 protein in controls to 46.4±2.0 in acute inflammation and from 66.8±2.2 fmol mg?1 protein in controls to 42.2±2.0 in chronic inflammation. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml?1 of rat tissue necrosis factor-? did not influence the binding indices to the calcium channels. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels.

Sattari, Saeed; Dryden, William F; Eliot, Lise A; Jamali, Fakhreddin

2003-01-01

325

Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats.  

PubMed

To know whether isoflavones are responsible for the hypocholesterolemic effect of soy protein, the effect on plasma cholesterol of isoflavone-free soy protein prepared by column chromatography was examined in rats. Five-week-old male Sprague-Dawley rats were fed cholesterol-enriched AIN-93G diets containing either 20% casein (CAS), 20% soy protein isolate (SPI), 20% isoflavone-free SPI (IF-SPI), 19.7% IF-SPI + 0.3% isoflavone-rich fraction (isoflavone concentrate, IC), or 20% CAS + 0.3% IC for 2 weeks. Plasma total cholesterol concentrations of rats fed SPI and IF-SPI were comparable and were significantly lower than that of rats fed CAS. The addition of IC to the CAS and IF-SPI did not influence plasma cholesterol level. Fecal steroid excretion of the three SPI groups was higher than that of the two CAS groups, whereas the addition of IC showed no effect. Thus, a significant fraction of the cholesterol-lowering effect of SPI in rats can be attributed to the protein content, but the isoflavones and other minor constituents may also play a role. PMID:12236704

Fukui, Kensuke; Tachibana, Nobuhiko; Wanezaki, Satoshi; Tsuzaki, Shinichi; Takamatsu, Kiyoharu; Yamamoto, Takashi; Hashimoto, Yukio; Shimoda, Tadahisa

2002-09-25

326

Reduced Expression of Nogo-A Leads to Motivational Deficits in Rats  

PubMed Central

Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased pre-pulse inhibition, and behavioral inflexibility. In the current study, we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation, and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex (PFC), dorsal striatum (dSTR), and nucleus accumbens (NAcc). Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A deficient rats exhibited lower break points and tended to have lower “highest completed ratios.” Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the PFC we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dSTR and the NAcc. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

Enkel, Thomas; Berger, Stefan M.; Schonig, Kai; Tews, Bjorn; Bartsch, Dusan

2014-01-01

327

Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.  

PubMed

Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. PMID:24656388

Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

2014-05-01

328

Plasma insulin-like growth factor I levels in rats are reduced by dietary supplementation of flaxseed or its lignan secoisolariciresinol diglycoside  

Microsoft Academic Search

Flaxseed and its lignan secoisolariciresinol diglycoside (SDG) inhibit mammary tumor development in rats. Increased plasma insulin-like growth factor I (IGF-I) concentrations are associated with increased breast cancer risk. Therefore, the effect of flaxseed (5%) or SDG (1.5 mg\\/day) supplementation on plasma IGF-I levels was examined in rats treated with or without N-methyl-N-nitrosourea (MNU). In MNU-free rats, flaxseed and SDG reduced

Sharon E. Rickard; Yvonne V. Yuan; Lilian U. Thompson

2000-01-01

329

Roux-en-Y gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats.  

PubMed

Roux-en-Y gastric bypass (RYGB) surgery leads to bone loss in humans, which may be caused by vitamin D and calcium malabsorption and subsequent secondary hyperparathyroidism. However, because these conditions occur frequently in obese people, it is unclear whether they are the primary causes of bone loss after RYGB. To determine the contribution of calcium and vitamin D malabsorption to bone loss in a rat RYGB model, adult male Wistar rats were randomized for RYGB surgery, sham-operation-ad libitum fed, or sham-operation-body weight-matched. Bone mineral density, calcium and phosphorus balance, acid-base status, and markers of bone turnover were assessed at different time points for 14 wk after surgery. Bone mineral density decreased for several weeks after RYGB. Intestinal calcium absorption was reduced early after surgery, but plasma calcium and parathyroid hormone levels were normal. 25-hydroxyvitamin D levels decreased, while levels of active 1,25-dihydroxyvitamin D increased after surgery. RYGB rats displayed metabolic acidosis due to increased plasma lactate levels and increased urinary calcium loss throughout the study. These results suggest that initial calcium malabsorption may play a key role in bone loss early after RYGB in rats, but other factors, including chronic metabolic acidosis, contribute to insufficient bone restoration after normalization of intestinal calcium absorption. Secondary hyperparathyroidism is not involved in postoperative bone loss. Upregulated vitamin D activation may compensate for any vitamin D malabsorption. PMID:24026074

Abegg, Kathrin; Gehring, Nicole; Wagner, Carsten A; Liesegang, Annette; Schiesser, Marc; Bueter, Marco; Lutz, Thomas A

2013-11-01

330

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.  

PubMed

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

Iwasa, Motoh; Kobayashi, Yoshinao; Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C; Takei, Yoshiyuki

2013-01-01

331

Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats[S  

PubMed Central

Acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased ?-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect.

Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K.; Pacheco-Lopez, Gustavo; Turnbull, Andrew V.; Langhans, Wolfgang; Mansouri, Abdelhak

2013-01-01

332

"Green odor" inhalation reduces the skin-barrier disruption induced by chronic restraint stress in rats: physiological and histological examinations.  

PubMed

We investigated whether inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) prevents the skin-barrier disruption induced by chronic restraint stress in rats. To this end, transepidermal water loss (TEWL) was measured as an index of the disruption of skin-barrier function, whereas light- and electron-microscope examinations were performed to observe histological changes in the skin of the stressed animals. In addition, the effects on TEWL induced by chronic administration of a glucocorticoid, dexamethasone (DEX), were examined. Chronic restraint stress (8 h per day for 14 days) increased TEWL (vehicle + stress group). This effect (and the chronic stress-induced increase in adrenal weight) was prevented in rats that inhaled green odor at the beginning of each day's restraint (2 h each day for 14 days; green odor + stress group). Electron-microscope studies revealed that rats in the green odor + stress group possessed sufficient intercorneocyte lipids to create an effective skin barrier, although these had apparently been decreased in the vehicle + stress group. Daily administration of DEX for 14 days increased TEWL. The present results suggest that chronic stress-induced disruption of the skin barrier in rats can be reduced or prevented by green odor (possibly at least in part through an inhibitory effect on the stress-induced activation of the hypothalamo-pituitary-adrenocortical axis). PMID:17566071

Fukada, Mika; Kaidoh, Toshiyuki; Ito, Ai; Yano, Tomomi; Hayashibara, Chie; Watanabe, Tatsuo

2007-07-01

333

Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats  

PubMed Central

The small (SK3) and intermediate (IK1) conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague–Dawley rats (250–300 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group (P < 0.05). The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.

Zhu, Jin-Hai; Jia, Rui-Peng; Xu, Lu-Wei; Wu, Jian-Ping; Wang, Zi-Zheng; Wang, Shu-Kui; Bo, Cheng-Jia

2010-01-01

334

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

PubMed

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge. PMID:23904096

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

2013-11-01

335

Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats  

PubMed Central

Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing ethanol-induced hepatocyte hyperproliferation. For 1 month, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total calories) diet as follows: either ethanol alone (Alc group) or ethanol in combination with 0.1 mg/kg body wt of all-trans RA (Alc+RA group), 2 mg/kg body wt of VE (Alc+VE group), or both together (Alc+RA+VE group). Control rats were pair-fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol. The ethanol-fed groups had three-fold higher hepatic CYP2E1 levels, 50% lower hepatic RA levels, and significantly increased hepatocyte proliferation when compared with the controls. The ethanol-fed rats given VE had more than four-fold higher hepatic VE concentrations than did ethanol-fed rats without VE, but this did not prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or hepatocellular hyperproliferation. Further, VE supplementation could not prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in vitro. These results show that VE supplementation can neither inhibit ethanol-induced changes in RA catabolism nor prevent ethanol-induced hepatocyte hyperproliferation in the rat liver.

Chung, Jayong; Veeramachaneni, Sudipta; Liu, Chun; Mernitz, Heather; Russell, Robert M.; Wang, Xiang-Dong

2009-01-01

336

Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.  

PubMed

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications. PMID:24406684

Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

2014-02-15

337

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

PubMed Central

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

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

2010-01-01

338

Gastric Bypass Surgery Causes Body Weight Loss Without Reducing Food Intake in Rats  

Microsoft Academic Search

Background  It is a common dogma that gastric bypass (GB) induces early satiety and consequent reductions in food intake and nutrient\\u000a absorption. The aim of the present study was to analyze feeding behavioral and metabolic changes in rats after GB.\\u000a \\u000a \\u000a \\u000a Methods  Male Sprague–Dawley rats at the ages of 23 and 42 weeks were placed in metabolic cages connected with a comprehensive laboratory\\u000a animal

Marianne W. Furnes; Karin Tømmerås; Carl-Jørgen Arum; Chun-Mei Zhao; Duan Chen

2008-01-01

339

Hemoglobin-glutamer 200 reduces reperfusion injury of the cold preserved rat liver by induction of heme oxygenase-1.  

PubMed

Microcirculatory failure after cold liver preservation and reperfusion impairs tissue oxygenation and causes additional organ damage. Hemoglobin-glutamer (HbG) 200 is a hemoglobin-based oxygen carrying solution capable to improve organ oxygenation. The aim of this study was to evaluate its potential to decrease reperfusion injury after cold liver preservation. Therefore, Wistar rat livers were stored at 4 degrees C for 24 h and reperfused in the isolated perfused rat liver model with a sanguineous perfusate for 180 min. The perfusate consisted of rat blood and Krebs-Henseleit solution (Group A), supplemented by either HES 6% (Group B), or HbG (Groups C and D). In Group D heme oxygenase (HO) activity was blocked by intraperitoneal tin protoporphyrin-IX application before organ harvest. HbG supplementation increased the perfusate hemoglobin by 3,3 g/dL. After 180 min reperfusion perfusate alanine aminotransferase levels (72 +/- 27 micro/L) were significantly reduced in Group C, compared with Groups A and B (140 +/- 28 micro/L and 203 +/- 62 micro/L, respectively). These results correlated with a significant increase of HO-1 expression and activity during reperfusion. These effects could be abolished by tin protoporphyrin-IX application. HbG has been proven to be effective to reduce cold liver preservation-reperfusion injury. The positive effect on reperfusion injury depends on the induction of HO-1, which increases the bilirubin production, an important antioxidant acting as intracellular radical scavenger. PMID:18395753

Topp, Stefan A; Krieg, Andreas; Koch, Alexander; Tidden, Carina M; Ramp, Uwe; Hohlfeld, Thomas; Macher, Arne; Schulte am Esch, Jan; Eisenberger, Claus F; Stoecklein, Nikolas H; Knoefel, Wolfram T

2008-12-01

340

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

PubMed

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

Sachdeva, S; Flora, S J S

2014-04-01

341

Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model.  

PubMed

Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug's antagonistic affinity to histamine H? receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H? receptor agonist and H? receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of olanzapine with betahistine significantly prevented (-45%) weight gain and reduced feeding efficiency compared to sole olanzapine treatment. Betahistine treatment alone had no effect on weight gain and food intake. Olanzapine reduced locomotor activity, but not betahistine. These findings demonstrate that olanzapine-induced body weight gain can partially be reduced by co-treatment with betahistine. Betahistine has H? receptor antagonistic effects to increase histamine release, which may augment its direct agonistic effects on H? receptors. These findings have important implications for clinical trials using betahistine to control antipsychotic-induced obesity side effects. PMID:22695490

Deng, Chao; Lian, Jiamei; Pai, Nagesh; Huang, Xu-Feng

2012-09-01

342

Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis.  

PubMed

Teriflunomide is an orally available anti-inflammatory drug that prevents T and B cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It is currently being developed for the treatment of multiple sclerosis (MS). We report here for the first time the anti-inflammatory effects of teriflunomide in the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE). Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at 3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores. Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease onset significantly reduced maximal and cumulative disease scores as compared to vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10 mg/kg, reduced the cumulative scores for the remaining course of the disease. Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and axonal loss when dosed prophylactically or therapeutically. In electrophysiological somatosensory evoked potential studies, therapeutic administration of teriflunomide, at the onset of disease, prevented both a decrease in waveform amplitude and an increase in the latency to waveform initiation in EAE animals compared to vehicle. Therapeutic dosing with teriflunomide at disease remission prevented a decrease in evoked potential amplitude, prevented an increase in latency, and enhanced recovery time within the CNS. PMID:19169851

Merrill, Jean E; Hanak, Susan; Pu, Su-Fen; Liang, Jinjun; Dang, Chelsea; Iglesias-Bregna, Deborah; Harvey, Brian; Zhu, Bin; McMonagle-Strucko, Kathleen

2009-01-01

343

NOS inhibition increases bubble formation and reduces survival in sedentary but not exercised rats  

Microsoft Academic Search

Previously we have shown that chronic as well as a single bout of exercise 20 h prior to a simulated dive protects rats from severe decompression illness (DCI) and death. However, the mechanism behind this protection is still not known. The present study determines the effect of inhibiting nitric oxide synthase (NOS) on bubble formation in acutely exercised and sedentary

U. Wisloff; Russell S. Richardson; Alf O. Brubakk

2003-01-01

344

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

Microsoft Academic Search

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.

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

1995-01-01

345

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...

346

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

Microsoft Academic Search

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%

Barbara H. D Luccia; M. Elizabeth Kunkel

2002-01-01

347

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

SciTech Connect

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

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

1990-05-01

348

Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex  

Microsoft Academic Search

Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in western society. We investigated possible changes in glutamate receptor levels in neonatal animals following ethanol exposure using radioligand binding and western blot analysis. We used a vapor chamber to administer ethanol to neonatal Wistar rats 3 h a day from postnatal day (PND) 4–9. A separation control group

Frederick P Bellinger; Mark S Davidson; Kuldip S Bedi; Peter A Wilce

2002-01-01

349

Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain  

Microsoft Academic Search

Exposure to stressful events and elevated level of stress hormones are associated with impaired spatial memory and neuronal damage in the hippocampus. These neurons are considered to be maintained by neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) and trk family of neurotrophin receptors. Male Wistar rats (6 weeks old) were exposed to immobilization

Takashi Ueyama; Yoshinori Kawai; Kiyomitsu Nemoto; Masashi Sekimoto; Shigenobu Toné; Emiko Senba

1997-01-01

350

Paracetamol reduces neuropathic pain-like behaviour in rats by potentiating serotonergic neurotransmission  

Microsoft Academic Search

Serotonin (5-HT) reuptake inhibitors are frequently used to treat neuropathic pain in humans. Sciatic nerve ligation in rats represents a predictive model to study molecules with a therapeutic potential in human neuropathic pain syndromes. In addition, it has been reported that in this model peripheral neuropathy is associated to a reduction of central 5-HT release. To evaluate the activity of

Beatrice Garrone; Lorenzo Polenzani; Stefano De Santi; Walter Moreci; Angelo Guglielmotti

351

Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.  

PubMed

The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents. PMID:24882157

Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S

2014-08-01

352

Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats.  

PubMed

Exposure to paraquat leads to acute lung injury and oxidative stress is widely accepted as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of water with dissolved molecular hydrogen to a saturated level (hydrogen water) prevents oxidative stress-induced diseases. Here, we investigated whether consumption of saturated hydrogen saline protects rats against paraquat-induced acute lung injury. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group; hydrogen water-only group (HW group); paraquat-only group (PQ group); paraquat and hydrogen water group (PQ + HW group). The rats in control group and HW group drank pure water or hydrogen water; the rats in PQ group and PQ + HW group were intraperitonealy injected with paraquat (35?mg/kg) and then provided pure water or hydrogen water. Both biochemical and histological lung alterations were measured. The results showed that hydrogen water ameliorated these alterations, demonstrating that hydrogen water alleviated paraquat-induced acute lung injury possibly by inhibition of oxidative damage. PMID:21318114

Liu, Shulin; Liu, Kan; Sun, Qiang; Liu, Wenwu; Xu, Weigang; Denoble, Petar; Tao, Hengyi; Sun, Xuejun

2011-01-01

353

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats  

Microsoft Academic Search

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient)

Milos Cekic; Sarah M. Cutler; Jacob W. VanLandingham; Donald G. Stein

2011-01-01

354

Aniracetam restores motivation reduced by satiation in a choice reaction task in aged rats  

Microsoft Academic Search

This study aims to examine the effects of aniracetam on satiation-induced poor performance in a choice reaction task. Aged rats that mastered the task under food restriction stably maintained the task performance for a long period. Satiation by successive free feeding greatly diminished the performance. Satiation resulted in a decreased % correct, increased % omission and prolonged choice reaction time,

Kazuo Nakamura; Mitsue Kurasawa

2001-01-01

355

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats  

Microsoft Academic Search

Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic

Bjørn Liaset; Lise Madsen; Qin Hao; Gabriel Criales; Gunnar Mellgren; Hanns-Ulrich Marschall; Philip Hallenborg; Marit Espe; Livar Frøyland; Karsten Kristiansen

2009-01-01

356

Olfactory ensheathing cells can reduce the tissue loss but not the cavity formation in contused spinal cord of rats.  

PubMed

In recent years, olfactory ensheathing cells (OECs) have been used as a therapeutic strategy to repair the anatomical structure and promote the function recovery of injured spinal cord in both animal and human. In this study, OECs were transplanted into contused spinal cords of adult rats. After dorsal laminectomy at T10 vertebra, spinal cord was injured by a force of 10 g with NYU II impactor from 25 mm above the exposed cord. The contused spinal cord received injections of OECs in DMEM or DMEM alone at one week after injury. The migration and distribution of OECs in the contused spinal cord were observed by the light microscope. The intact tissue area, injured tissue area, cavity size, number of myelinated nerve fibers and neurons labeled by CB-HRP in T8 segment were measured and counted by the semi-quantitative techniques at 6 weeks after transplantation. Locomotor ability and conductive function of the spinal cord were evaluated by the BBB score and cortical somatosensory evoked potentials (CSEP) recording. OECs were found in both lesion site and tissue near the lesion. The intact tissue area was significantly larger in the OECs-transplanted rats than that in the DMEM-injected animals, whereas the injured tissue area was significantly smaller in the OECs-rats than that in the DMEM-rats. The number of myelinated nerve fibers in the lesion site and preserved neurons in T8 was significantly greater in the OECs-group than in the DMEM-group, but the cavity size detected was not significantly different between the two groups. The BBB score and CSEP recording showed a better performance of locomotor ability and conductive function in the OECs-transplanted rats than in the DMEM-injected animals. These results indicate that OECs can counteract secondary tissue degeneration after spinal cord injury. Although they cannot reduce the cavity formation, they can promote morphological preservation and functional improvement of the contused spinal cord. PMID:21306739

Li, Bing Cang; Li, Yue; Chen, Li Fa; Chang, Jie Yuan; Duan, Zhao Xiao

2011-04-15

357

Treatment with Lindera strychnifolia reduces blood pressure by decreasing sympathetic nerve activity in spontaneously hypertensive rats.  

PubMed

Lindera strychnifolia (Tendai-Uyaku), a medicinal plant, has long been used for the treatment of cardiac, renal and rheumatic diseases in Japan. We investigated the effect of Lindera strychnifolia on systolic blood pressure, cardiac function, and plasma noradrenaline levels in rats. Spontaneously hypertensive rats (SHR) were given free access to water or extract solution of Lindera strychnifolia, which was extracted with a ratio of 10 g Lindera strychnifolia roots/20 ml water. Systolic blood pressure was measured by using a tail-cuf sphygmomanometer twice a week from 10 to 30 weeks of age, and compared to the age-matched Wistar Kyoto rats (WKY) as a control group. At 30 weeks of age, heart function was measured by echocardiography and blood samples were taken for detection of plasma noradrenaline levels, and rats were then sacrificed. Systolic blood pressure gradually increased from 10 to 30 weeks of age in the SHR group, while it did not change in the WKY group. In the Lindera-treated SHR group, the increase in systolic blood pressure was significantly attenuated from 21 to 30 weeks of age. Echocardiography showed a significant increase in ejection fraction in the Lindera-treated SHR group (60.4 +/- 7.8%) as compared to the SHR group (39.7 +/- 23.4%). Plasma noradrenaline levels were significantly decreased in Lindera-treated SHR group compared to the SHR group. These results suggest that Lindera strychnifolia has an anti-hypertensive effect and improves cardiac function in spontaneous hypertensive rats. These effects may be related to the decrease in plasma noradrenaline levels by Lindera strychnifolia. PMID:20503472

Shimomura, Masayuki; Ushikoshi, Hiroaki; Hattori, Arihiro; Murata, Ichijiro; Ohno, Yasushi; Aoyama, Takuma; Kawasaki, Masanori; Nishigaki, Kazuhiko; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Minatoguchi, Shinya

2010-01-01

358

Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats  

PubMed Central

Background Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain. Methods The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction. Results In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor ? (TNF?), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNF? and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group. Conclusions In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

Kwon, So-Young; Yeom, Jae Hwa

2014-01-01

359

Injection of Oxotremorine in Nucleus Accumbens Shell Reduces Cocaine But Not Food Self-Administration in Rats  

PubMed Central

Mesencephalic dopamine neurons form synapses with acetylcholine (ACh)-containing interneurons in the nucleus accumbens (NAcc). Although their involvement in drug reward has not been systematically investigated, these large aspiny interneurons may serve an important integrative function. We previously found that repeated activation of nicotinic cholinergic receptors enhanced cocaine intake in rats but the role of muscarinic receptors in drug reward is less clear. Here we examined the impact of local changes in muscarinic receptor activation within the NAcc on cocaine and food self-administration in rats trained on a progressive ratio (PR) schedule of reinforcement. Animals were given a minimum of 9 continuous days of drug access before testing in order to establish a stable breaking point (BP) for intravenous cocaine infusions (0.75 mg/kg/infusion). Rats in the food group acquired stable responding on the PR schedule within 7 days. On the test day, rats were bilaterally infused in the NAcc with the muscarinic receptor agonist oxotremorine methiodide (OXO: 0.1, 0.3 or 1 nmol/side), OXO plus the M1 selective antagonist pirenzepine (PIRENZ; 0.3 nmol/side) or aCSF 15 min before cocaine or food access. OXO dose dependently reduced BP values for cocaine reinforcement (-17%, -44% [p<0.05] and -91% [p<0.0001] for 0.1, 0.3 and 1.0 nmol, respectively) and these reductions dissipated by the following session. Pretreatment with PIRENZ blocked the BP-reducing effect of 0.3 nmol OXO. Notably, OXO (0.1, 0.3 and 1.0 nmol/side) injection in the NAcc did not affect BP for food reward. The results suggest that muscarinic ACh receptors in the caudomedial NAcc may play a role in mediating the behavior reinforcing effects of cocaine. Section: Neuropharmacology, Neuropharmacology and other forms of Intracellular Communication

Mark, Gregory P.; Kinney, Anthony E.; Grubb, Michele C.; Zhu, Xiaoman; Finn, Deborah A.; Mader, Sarah L.; Berger, S. Paul; Bechtholt, Anita J.

2006-01-01

360

Olprinone reduces ischemia/reperfusion-induced acute renal injury in rats through enhancement of cAMP.  

PubMed

Activated leukocytes are implicated in development of ischemia/reperfusion (I/R)-induced organ injuries. Phosphodiesterase 3 inhibitors have anti-inflammatory effects by preventing cyclic adenosine monophosphate (cAMP) degradation. We examined the effects of olprinone, a specific phosphodiesterase 3 inhibitor, on I/R-induced acute renal injury model in rats. Forty-five minute renal I/R was induced in uni-nephrectomized rats. Rats were divided into a vehicle group, an olprinone group, and a dibutyril (DB) cAMP group. Olprinone (0.2 microg/kg/minute) infusion began 30 min after reperfusion and continued for 3 h. DBcAMP (5 mg/kg), a stable analog of cAMP, was intraperitoneally administered 5 min after reperfusion to clarify the effect of cAMP in our model. Olprinone reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the outer medulla. Hemodynamic status was not affected by olprinone. I/R-induced a decrease in renal tissue blood flow, an increase in renal vascular permeability, and an enhancement of leukocyte activation, reflected by renal tissue levels of myeloperoxidase activity, and the tissue levels of cytokine-induced neutrophil chemoattractant (an equivalent of human interleukin 8) and tumor necrosis factor-alpha were all significantly decreased by olprinone. Olprinone also increased the renal tissue and plasma levels of cAMP in rats subjected to renal I/R. DBcAMP showed similar effects. Our results indicated that olprinone reduced the I/R-induced acute renal injury, probably by inhibiting leukocyte activation. The effects of olprinone could be explained through its action on cAMP levels. PMID:16135969

Mizutani, Akio; Murakami, Kazunori; Okajima, Kenji; Kira, Shin-Ichiro; Mizutani, Sachiko; Kudo, Kyosuke; Takatani, Junji; Goto, Koji; Hattori, Seiji; Noguchi, Takayuki

2005-09-01

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