Sample records for rat forelimb reduces

  1. In vivo static creep loading of the rat forelimb reduces ulnar structural properties at time-zero and induces damage-dependent woven bone formation.

    PubMed

    Lynch, Jennifer A; Silva, Matthew J

    2008-05-01

    Periosteal woven bone forms in response to stress fractures and pathological overload. The mechanical factors that regulate woven bone formation are poorly understood. Fatigue loading of the rat ulna triggers a woven bone response in proportion to the level of applied fatigue displacement. However, because fatigue produces damage by application of cyclic loading it is unclear if the osteogenic response is due to bone damage (injury response) or dynamic strain (adaptive response). Creep loading, in contrast to fatigue, involves application of a static force. Our objectives were to use static creep loading of the rat forelimb to produce discrete levels of ulnar damage, and subsequently to determine the bone response over time. We hypothesized that 1) increases in applied displacement during loading correspond to ulnae with increased crack number, length and extent, as well as decreased mechanical properties; and 2) in vivo creep loading stimulates a damage-dependent dose-response in periosteal woven bone formation. Creep loading of the rat forelimb to progressive levels of sub-fracture displacement led to progressive bone damage (cracks) and loss of whole-bone mechanical properties (especially stiffness) at time-zero. For example, loading to 60% of fracture displacement caused a 60% loss of ulnar stiffness and a 25% loss of strength. Survival experiments showed that woven bone formed in a dose-dependent manner, with greater amounts of woven bone in ulnae that were loaded to higher displacements. Furthermore, after 14 days the mechanical properties of the loaded limb were equal or superior to control, indicating functional repair of the initial damage. We conclude that bone damage created without dynamic strain triggers a woven bone response, and thus infer that the woven bone response reported after fatigue loading and in stress fractures is in large part a response to bone damage. PMID:18295561

  2. In Vivo Static Creep Loading of the Rat Forelimb Reduces Ulnar Structural Properties at Time-Zero and Induces Damage-Dependent Woven Bone Formation

    PubMed Central

    Lynch, Jennifer A.; Silva, Matthew J.

    2008-01-01

    Periosteal woven bone forms in response to stress fractures and pathological overload. The mechanical factors that regulate woven bone formation are poorly understood. Fatigue loading of the rat ulna triggers a woven bone response in proportion to the level of applied fatigue displacement. However, because fatigue produces damage by application of cyclic loading it is unclear if the osteogenic response is due to bone damage (injury response) or dynamic strain (adaptive response). Creep loading, in contrast to fatigue, involves application of a static force. Our objectives were to use static creep loading of the rat forelimb to produce discrete levels of ulnar damage, and subsequently to determine the bone response over time. We hypothesized that 1) increases in applied displacement during loading correspond to ulnae with increased crack number, length and extent, as well as decreased mechanical properties; and 2) in vivo creep loading stimulates a damage-dependent dose-response in periosteal woven bone formation. Creep loading of the rat forelimb to progressive levels of sub-fracture displacement led to progressive bone damage (cracks) and loss of whole-bone mechanical properties (especially stiffness) at time-zero. For example, loading to 60% of fracture displacement caused a 60% loss of ulnar stiffness and a 25% loss of strength. Survival experiments showed that woven bone formed in a dose-dependent manner, with greater amounts of woven bone in ulnae that were loaded to higher displacements. Furthermore, after 14 days the mechanical properties of the loaded limb were equal or superior to control, indicating functional repair of the initial damage. We conclude that bone damage created without dynamic strain triggers a woven bone response, and thus infer that the woven bone response reported after fatigue loading and in stress fractures is in large part a response to bone damage. PMID:18295561

  3. Characteristics of H- and M-waves recorded from rat forelimbs.

    PubMed

    Hosoido, Taisei; Motoyama, Sachiko; Goto, Megumi; Mori, Futoshi; Tajima, Takamitsu; Hirata, Hajime; Wada, Naomi

    2009-02-01

    The Hoffman reflex (H-reflex) is a useful tool for studying the functional aspects of the spinal cord without anesthesia and/or damage to the body. H-reflex studies are performed mainly in the hindlimbs. The purpose of the present study was to evaluate the characteristics of the H-reflex in the forelimbs and hindlimbs in rats anesthetized with ketamine-HCl. H- and M-waves were recorded from the interosseous muscles after electrical stimulation of the n. lateral plantar of the hindlimb and n. medialis of the forelimb. Hmax/Mmax values were significantly smaller in the forelimbs than in the hindlimbs. Furthermore, paired-pulse attenuation tended to be stronger in the forelimbs than in the hindlimbs. These findings suggest that control by descending and/or propriospinal pathways is stronger in the forelimbs than in the hindlimbs in rats. PMID:19056465

  4. Cortical PKC inhibition promotes axonal regeneration of the corticospinal tract and forelimb functional recovery after cervical dorsal spinal hemisection in adult rats.

    PubMed

    Wang, Xiaofei; Hu, Jianguo; She, Yun; Smith, George M; Xu, Xiao-Ming

    2014-11-01

    Our previous study shows that conventional protein kinases C (cPKCs) are key signaling mediators that are activated by extracellular inhibitory molecules. Inhibition of cPKC by intrathecal infusion of a cPKC inhibitor, GÖ6976, into the site of dorsal hemisection (DH) induces regeneration of lesioned dorsal column sensory, but not corticospinal tract (CST), axons. Here, we investigated whether a direct cortical delivery of GÖ6976 into the soma of corticospinal neurons promotes regeneration of CST and the recovery of forelimb function in rats with cervical spinal cord injuries. We report that cortical delivery of GÖ6976 reduced injury-induced activation of conventional PKC? and PKC?1 in CST neurons, promoted regeneration of CST axons through and beyond a cervical DH at C4, formed new synapses on target neurons caudal to the injury, and enhanced forelimb functional recovery in adult rats. When combined with lenti-Chondroitinase ABC treatment, cortical administration of GÖ6976 promoted even greater CST axonal regeneration and recovery of forelimb function. Thus, this study has demonstrated a novel strategy that can promote anatomical regeneration of damaged CST axons and partial recovery of forelimb function. Importantly, such an effect is critically dependent on the efficient blockage of injury-induced PKC activation in the soma of layer V CST neurons. PMID:23810979

  5. 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

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

    2000-09-15

    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

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

    PubMed

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

    2015-02-01

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

  7. Measuring forelimb force control and movement in Fischer 344/Brown Norway rats: effects of age and lorazepam.

    PubMed

    Stanford, John A; Osterhaus, Gregory L; Vorontsova, Elena; Fowler, Stephen C

    2006-12-01

    The purpose of this study was to measure forelimb force control and movement kinetics in rats, as they are affected by normal aging and the benzodiazepine lorazepam. Young (6 months), middle-aged (18 months), and aged (24 months) rats were trained to emit discrete forelimb responses on an isometric force disk within a 20-25 g force band for water reinforcement. Dependent variables included number of responses, percentage of reinforced responses, peak response forces, and inter-response times. Inter-response times were divided into two categories: inter-response times <0.5 s (reflecting rapid, discrete forelimb responses) and inter-response times 4-8 s (reflecting movement sequences). Aged rats exhibited no apparent deficits in forelimb force control. Although older rats emitted fewer responses than younger rats, their response accuracy was greater. Peak forces did not differ among the groups. Both categories of inter-response times were slower in the aged group, reflecting slowed discrete movements and movement sequencing. Lorazepam increased the number of responses and peak forces, decreased response accuracy, and lengthened inter-response times within the 4-8 s range (but not the <0.5 s range) in all age groups. The results suggest that movement sequences may be more sensitive to the effects of acute benzodiazepines than rapid discrete movements. PMID:17110798

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

    Microsoft Academic Search

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

    2000-01-01

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

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

    PubMed

    Anderson, Kim D; Gunawan, Ardi; Steward, Oswald

    2007-08-01

    There is increasing interest in developing rodent models for cervical spinal cord injury (SCI) and techniques to assess forelimb motor function. Previously, we demonstrated that in rats, complete unilateral hemisection at cervical level five (C5) permanently eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion [Anderson, K.D., Gunawan, A., Steward, O., 2005. Quantitative behavioral analysis of forepaw function after cervical spinal cord injury in rats: Relationship to the corticospinal tract. Exp. Neurol. 194, 161-174]. Here, we analyzed the functional consequences of partial lesions that damaged tracts/cells located in the medial vs. lateral portion of the spinal cord. Female Sprague-Dawley rats were trained on the Grip Strength Meter (GSM) and the food pellet reaching task. Rats then received either a "medial lesion" that destroyed an approximately 0.5 mm wide zone from the midline laterally (which included the dorsal column) or "lateral lesion" that destroyed the lateral column at C5 and were tested for 8 weeks. Rats with histologically-verified medial lesions exhibited a complete loss of gripping ability for 7 weeks post-injury; only 1 of 4 animals exhibited any recovery of grip strength, and this occurred at 54 days. In contrast, rats with lateral lesions exhibited deficits, but the majority (7/10) recovered the ability to grip by 43 days post-injury. Interestingly, when tested on the food retrieval task, rats with medial lesions exhibited deficits that recovered; rats with lateral lesions exhibited more permanent deficits. These results suggest that different spinal circuits are involved in recovery of grip strength vs. recovery of skilled reaching. PMID:17603042

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

    PubMed

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

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

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

    PubMed Central

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

    2011-01-01

    Brain machine interfaces (BMIs) use signals from the brain to control a device such as a computer cursor. Various types of signals have been used as BMI inputs, from single-unit action potentials to scalp potentials. Recently, intermediate-level signals such as subdural field potentials have also shown promise. These different signal types are likely to provide different amounts of information, but we don't 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 (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 four targets in two dimensions. We decoded 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. PMID:21508491

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

    PubMed Central

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

    2014-01-01

    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. PMID:24847198

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

    PubMed Central

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

    2013-01-01

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

  15. An analysis of the representation of the forelimb in the ventrobasal thalamic complex of the albino rat.

    PubMed Central

    Angel, A; Clarke, K A

    1975-01-01

    1. Glass micro-electrodes have been used to record from a total of 998 units situated in the ventrobasal thalamic complex in the deeply anaesthetized albino rat. 2. Of these units 889 responded to electrical stimulation of the contralateral forelimb and fifty-one to the contralateral hind limb. The remaining units consisted of those with receptive fields on the trunk, head and those which responded to stimulation of more than one limb. Only the latter group of units showed any spontaneous activity in the absence of intentional stimulation. 2. Of the units which responded to electrical stimulation of the contralateral forelimb the receptive fields, modality and latencies of response were accurately determined for 505 units. The mean latency to supramaximal stimulation at the wrist was 4.49 (+/- 0.04 S.E. of mean) msec; and to mechanical stimulation (for 146 of these units) at the centre of the receptive field 6.58 (+/- 0.12) msec. The modalities were distributed as follows: light pressure, 391; heavy pressure, 47; hair movement, 40; claw sensitive, 15 and joint movement, 12 units. 4. The forelimb representation within the ventrobasal thalamic complex was somatotopically organized, the over-all appearance being that of an incompletely closed fist, palmar surface uppermost, thumb media, with the wrist caudal and the digital tips rostral and dorsal. 5. The central projection was distorted, some parts showing expanded representation, notably the tips of digits II and III and the medial wrist pad. Other parts were contracted, e.g. the wrist, forearm and shoulder. 6. Units with receptive fields consisting of the whole of a walking pad had shorter mean latencies, to tactile stimulation, than those whose field was a single spot on a pad. 7. Units were found to show an abolute unresponsive time to the second of a pair of identical supramaximal electrical stimuli of up to 50 msec, and a relative unresponsive time which could last up to 500 msec. The absolute unresponsive and relative unresponsive times to the second of a pair of tactile stimuli was shorter being 30 and 150 msec respectively. 8. The effect of decortication was to increase the excitability of thalamic units to peripheral stimulation both in the initial and later discharges. PMID:1177098

  16. Loss and Spontaneous Recovery of Forelimb Evoked Potentials in both the Adult Rat Cuneate Nucleus and Somatosensory Cortex following Contusive Cervical Spinal Cord Injury

    PubMed Central

    Onifer, Stephen M.; Nunn, Christine D.; Decker, Julie A.; Payne, Beth N.; Wagoner, Michelle R.; Puckett, Aaron H.; Massey, James M.; Armstrong, James; Kaddumi, Ezidin G.; Fentress, Kimberly G.; Wells, Michael J.; West, Robert M.; Calloway, Charles C.; Schnell, Jeffrey T.; Whitaker, Christopher M.; Burke, Darlene A.; Hubscher, Charles H.

    2007-01-01

    Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPS) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-C6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPS) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI. PMID:17678895

  17. Selective Forelimb Impairment in Rats Expressing a Pathological TDP-43 25?kDa C-terminal Fragment to Mimic Amyotrophic Lateral Sclerosis

    PubMed Central

    Dayton, Robert D; Gitcho, Michael A; Orchard, Elysse A; Wilson, Jon D; Wang, David B; Cain, Cooper D; Johnson, Jeffrey A; Zhang, Yong-Jie; Petrucelli, Leonard; Mathis, J Michael; Klein, Ronald L

    2013-01-01

    Pathological inclusions containing transactive response DNA-binding protein 43?kDa (TDP-43) are common in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). TDP-43 normally localizes predominantly to the nucleus, but during disease progression, it mislocalizes to the cytoplasm. We expressed TDP-43 in rats by an adeno-associated virus (AAV9) gene transfer method that transduces neurons throughout the central nervous system (CNS). To mimic the aberrant cytoplasmic TDP-43 found in disease, we expressed a form of TDP-43 with mutations in the nuclear localization signal sequence (TDP-NLS). The TDP-NLS was detected in both the cytoplasm and the nucleus of transduced neurons. Unlike wild-type TDP-43, expression of TDP-NLS did not induce mortality. However, the TDP-NLS induced disease-relevant motor impairments over 24 weeks. We compared the TDP-NLS to a 25?kDa C-terminal proaggregatory fragment of TDP-43 (TDP-25). The clinical phenotype of forelimb impairment was pronounced with the TDP-25 form, supporting a role of this C-terminal fragment in pathogenesis. The results advance previous rodent models by inducing cytoplasmic expression of TDP-43 in the spinal cord, and the non-lethal phenotype enabled long-term study. Approaching a more relevant disease state in an animal model that more closely mimics underlying mechanisms in human disease could unlock our ability to develop therapeutics. PMID:23689600

  18. Rat Pups Reduce Ultrasonic Vocalization After Exposure

    E-print Network

    Barr, Gordon A.

    Rat Pups Reduce Ultrasonic Vocalization After Exposure to an Adult Male Rat Christoph P to the male emitted significantly fewer ultrasonic vocalizations than controls, but did not differ. Keywords: rat; ultrasonic vocalization; immobility; infanticide; anxiety-like behavior Animals have

  19. Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb.

    PubMed

    Galtrey, Clare M; Fawcett, James W

    2007-03-01

    The majority of human peripheral nerve injuries occur in the upper limb but the majority of studies in the rat are performed in the hindlimb. The upper and lower limbs differ in dexterity and control by supraspinal systems, so an upper limb model is a better representation of the common form of human injury. The purpose of this study was to further develop a rat model involving lesions of the median and ulnar nerves. To produce different degrees of misdirection of axons following nerve repair, we studied nerve crush, cut and repair of the two nerves, and cut and repair with crossover. Assessment of functional recovery was performed using a battery of motor and sensory tests: the staircase test, which assesses skilled forepaw reaching; grip strength meter, which assesses grip strength; pawprint analysis, which assesses toe spread and print length; horizontal ladder, which assesses forepaw placement during skilled locomotion; modified Randall-Selitto device and electronic von Frey probes, which assess fine touch; and cold probes, which assess temperature sensation. All tests revealed deficits in forepaw function after nerve injury except the print length and modified Randall-Selitto device. The time course of functional recovery was observed over 15 weeks. The final degree of functional recovery achieved was related to the misdirection of axon regeneration. The tests that most clearly revealed the effects of axon misdirection on function were the skilled paw reaching and grip strength tests. The lesion model and functional tests that we have developed will be useful in testing therapeutic strategies for treating the consequences of inaccurate axon regeneration following peripheral nerve injury in humans. PMID:17374098

  20. Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.

    PubMed

    Khaing, Zin Z; Geissler, Sydney A; Jiang, Shan; Milman, Brian D; Aguilar, Sandra V; Schmidt, Christine E; Schallert, Timothy

    2012-02-10

    Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies. PMID:22022897

  1. Neuropeptide FF reduces food intake in rats

    Microsoft Academic Search

    Takashi Murase; Hiroshi Arima; Kunikazu Kondo; Yutaka Oiso

    1996-01-01

    The effect of neuropeptide FF (NPFF), a mammalian FMRFamide-like peptide with antiopioid activity, on food intake was investigated in food-deprived rat. The ICV administration of NPFF (5 or 10 ?g\\/rat) reduced food intake during the first 60 min after administration. ICV injection of naloxone (10 or 100 ?g\\/rat), an opioid antagonist, also decreased food intake. However, the combination of NPFF

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  3. Skilled forelimb movements in prey catching and in reaching by rats ( Rattus norvegicus) and opossums ( Monodelphis domestica): relations to anatomical differences in motor systems

    Microsoft Academic Search

    Tammy L. Ivanco; Sergio M. Pellis; Ian Q. Whishaw

    1996-01-01

    Traditional anatomical\\/behavioral classifications suggest that rats and opossums have simple motor systems and are impoverished with respect to their ability to make prehensile movements. Nevertheless, the motor system in rats and opossums represent extremes in relative size and complexity suggesting that a behavioral analysis of the movement competencies of these species will provide insights into the significance of such anatomical

  4. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    PubMed Central

    Cui, Guiyun; Yang, Xinxin; Wang, Xiaoying; Zhang, Zunsheng; Yue, Xuanye; Shi, Hongjuan; Shen, Xia

    2014-01-01

    Background Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID). The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum) and output (globus pallidus, substantia nigra) regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved. Methods A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally) and benserazide (12.5 mg/kg, intraperitoneally) for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg) on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg) on the expression of Arc and proenkephalin was also evaluated. Results Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg) reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg) significantly improved stepping of the lesioned forepaw. Real-time polymerase chain reaction showed that Arc and proenkephalin levels were reduced by chronic ranitidine (10 mg/kg) in dyskinetic rats. Conclusion These data indicate that ranitidine is a good adjunct for reducing LID in rats with dyskinesia. Inhibition of dopamine D1-mediated activation in the medium spiny neurons may account for the antidyskinetic effects of ranitidine in rats with dyskinesia. PMID:24379672

  5. Ivermectin reduces sexual behavior in female rats.

    PubMed

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

    2014-01-01

    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

  6. Forelimb biomechanics of nonavian theropod dinosaurs in predation

    Microsoft Academic Search

    Kenneth Carpenter

    2002-01-01

    Theoretical models of theropod forelimb biomechanics are often tainted with preconceived ideas. Actualistic modeling using\\u000a specimens and casts, coupled with CAT-scans and dissections of extant vertebrate forelimbs, demonstrates that forelimb motion\\u000a in theropods is considerably less than hypothetical models indicate. The forelimbs ofCoelophysis, cf.Coelurus, Allosaurus, Deinonychus, andTyrannosaurus were investigated. Motion at the shoulder, elbow, wrist, and digits were analyzed and

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  9. TRIMETHYLTIN REDUCES RECURRENT INHIBITION IN RATS

    EPA Science Inventory

    Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pul...

  10. Reduced neurons in the ileum of proctocolectomized rat models.

    PubMed

    Zhao, Chun-Mei; Myrvold, Helge E; Chen, Duan

    2014-11-29

    Ileal pouch-anal anastomosis (IPAA) is the operation of choice following proctocolectomy for patients who suffer from ulcerative colitis and familial adenomatous polyposis. The aim of this study was to morphologically examine the neurons, endocrine cells and mast cells in the ileum of rats subjected to proctocolectomy followed by three different types of ileoanal anastomosis. Rats were subjected to either sham operation or proctocolectomy followed by ileoanal anastomosis end-to-end, side-to-end or IPAA (J-pouch). In comparison to sham-operated rats, the body weight was reduced in rats that underwent proctocolectomy with end-to-end or side-to-end, but not IPAA procedure. In all three models of ileoanal anastomosis, the ileum displayed crypt hyperplasia with a chronic inflammatory infiltrate located in the interstitium, hyperplasia of goblet cells, but reduced protein gene product 9.5 (PGP 9.5)-immunoreactive neurons in the mucosa as well as submucosa. Numbers of endocrine cells in the mucosa (chromogranin A immunostaining) and mast cells in the mucosa and submucosa (Astra blue staining) were unchanged after proctocolectomy. In conclusion, neurons, but neither endocrine cells nor mast cells, were reduced in the ileum of proctocolectomized rats followed by either of three different types of ileoanal anastomosis. PMID:25432768

  11. Red maca (Lepidium meyenii) reduced prostate size in rats

    PubMed Central

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

    2005-01-01

    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. PMID:15661081

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

    PubMed Central

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

    2009-01-01

    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. PMID:19515923

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

    PubMed Central

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

    2014-01-01

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

  14. Oral administration of hyaluronan reduces bone turnover in ovariectomized rats.

    PubMed

    Ma, Jenny; Granton, Patrick V; Holdsworth, David W; Turley, Eva A

    2013-01-16

    The effect of oral hyaluronan (HA) on bone loss in ovariectomized (OVX) 3-month-old rats was measured using serum markers of bone turnover and bone mineral density. OVX rats were administered 1 mg/kg HA (OVX + HA) or phosphate-buffered saline (PBS) (OVX + PBS) by oral gavage (5 days/week for 54 days). Additional controls included sham ovariectomy with PBS gavage (Sham + PBS) and no treatment. Oral administration of HA resulted in approximately 50% (p < 0.05) increases in serum HA. Gel filtration analyses showed this was high molecular weight HA (300-500 kDa). Osteopenia was mild due to the young age of the animals. Thus, ovariectomy resulted in a 30% increase in serum collagen N-terminal telopeptides (p < 0.001), a 20% increase in serum nitrate/nitrite levels (p = 0.05), and a 5-6% decrease in femur bone mineral density/content (p < 0.05). HA gavage blunted the development of osteopenia in this model as determined by preventing the 30% increase in serum collagen N-terminal telopeptide levels (p < 0.001) and by reducing bone mineral content loss from 6 to 4%. These results show that oral supplements of HA (gavage solution, 0.12% solution) significantly reduce bone turnover associated with mild osteopenia in rats. PMID:23256527

  15. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

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

    2009-06-01

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

  16. Functional differentiation of trailing and leading forelimbs during locomotion on the ground and on a horizontal branch in the European red squirrel (Sciurus vulgaris, Rodentia).

    PubMed

    Schmidt, André

    2011-06-01

    Mammalian locomotion is characterized by the frequent use of in-phase gaits in which the footfalls of the left and right fore- or hindlimbs are unevenly spaced in time. Although previous studies have identified a functional differentiation between the first limb (trailing limb) and the second limb (leading limb) to touch the ground during terrestrial locomotion, the influence of a horizontal branch on limb function has never been explored. To determine the functional differences between trailing and leading forelimbs during locomotion on the ground and on a horizontal branch, X-ray motion analysis and force measurements were carried out in two European red squirrels (Sciurus vulgaris, Rodentia). The differences observed between trailing and leading forelimbs were minimal during terrestrial locomotion, where both limbs fulfill two functions and go through a shock-absorbing phase followed by a generating phase. During locomotion on a horizontal branch, European red squirrels reduce speed and all substrate reaction forces transmitted may be due to the reduction of vertical oscillation of the center of mass. Further adjustments during locomotion on a horizontal branch differ significantly between trailing and leading forelimbs and include limb flexion, lead intervals, limb protraction and vertical displacement of the scapular pivot. Consequently, trailing and leading forelimbs perform different functions. Trailing forelimbs function primarily as shock-absorbing elements, whereas leading forelimbs are characterized by a high level of stiffness. This functional differentiation indicates that European red squirrels 'test' the substrate for stability with the trailing forelimb, while the leading forelimb responds to or counteracts swinging or snapping branches. PMID:21658923

  17. 2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats.

    PubMed

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

    2013-01-01

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

  18. Forelimb and hindlimb forces in walking and galloping primates.

    PubMed

    Hanna, J B; Polk, J D; Schmitt, D

    2006-08-01

    One trait that distinguishes the walking gaits of most primates from those of most mammalian nonprimates is the distribution of weight between the forelimbs and hindlimbs. Nonprimate mammals generally experience higher vertical peak substrate reaction forces on the forelimb than on the hindlimb. Primates, in contrast, generally experience higher vertical peak substrate reaction forces on the hindlimb than on the forelimb. It is currently unclear whether this unusual pattern of force distribution characterizes other primate gaits as well. The available kinetic data for galloping primates are limited and present an ambiguous picture about peak-force distribution among the limbs. The present study investigates whether the pattern of forelimb-to-hindlimb force distribution seen during walking in primates is also displayed during galloping. Six species of primates were video-recorded during walking and galloping across a runway or horizontal pole instrumented with a force-plate. The results show that while the force differences between forelimb and hindlimb are not significantly different from zero during galloping, the pattern of force distribution is generally the same during walking and galloping for most primate species. These patterns and statistical results are similar to data collected during walking on the ground. The pattern of limb differentiation exhibited by primates during walking and galloping stands in contrast to the pattern seen in most nonprimate mammals, in which forelimb forces are significantly higher. The data reported here and by Demes et al. ([1994] J. Hum. Evol. 26:353-374) suggest that a relative reduction of forelimb vertical peak forces is part of an overall difference in locomotor mechanics between most primates and most nonprimate mammals during both walking and galloping. PMID:16425190

  19. A relationship between hepatic metabolism of reduced lantadene A and its toxicity in rats and sheep.

    PubMed

    Pass, M A; Goosem, M W; Pollitt, S

    1985-01-01

    The metabolism of the cholestatic triterpene acid reduced lantadene A has been studied in susceptible and resistant rats and in sheep which are susceptible to intoxication. Sheep and susceptible female rats produced a similar major metabolite and rats produced a second metabolite which was a glucuronide. These metabolites were also observed in extracts of bile canalicular membranes prepared from intoxicated rats. Resistant male and female rats produced a similar major metabolite which was different to those synthesized by susceptible animals. It is concluded that in rats and sheep there is a correlation between the type of metabolites produced in the liver and the susceptibility to intoxication by reduced lantadene A. PMID:2866921

  20. Anatomical, architectural, and biochemical diversity of the murine forelimb muscles.

    PubMed

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

    2012-11-01

    We characterized the architecture, fiber type, titin isoform distribution, and collagen content of 27 portions of 22 muscles in the murine forelimb. The mouse forelimb 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, whereas 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 forelimb, as well as 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 with 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. PMID:22938020

  1. Trichloroethylene Metabolism in the Rat Ovary Reduces Oocyte Fertilizability

    PubMed Central

    Wu, Katherine Lily; Berger, Trish

    2007-01-01

    Exposure to trichloroethylene (TCE, an environmental toxicant) reduced oocyte fertilizability in the rat. In vivo, TCE may be metabolized by cytochrome P450 dependent oxidation or glutathione conjugation in the liver or kidneys, respectively. Cytochrome P450 dependent oxidation is the higher affinity pathway. The primary isoform of cytochrome P450 to metabolize TCE in the liver, cytochrome P450 2E1, is present in the rodent ovary. Ovarian metabolism of TCE by the oxidative pathway and the production of reactive oxygen species may occur given the presence of the metabolizing enzyme. The objectives of this study were to define the sensitive interval of oocyte growth to TCE exposure, and to determine if TCE exposure resulted in the formation of ovarian protein carbonyls, an indicator of oxidative damage. Rats were exposed to TCE in drinking water (0.45% TCE (v/v) in 3% Tween) or 3% Tween (vehicle-control) during three 4–5 day intervals of oocyte development preceding ovulation. Oocytes from TCE-exposed females were less fertilizable compared with vehicle-control oocytes. Immunohistochemical labeling of ovaries and Western blotting of ovarian proteins demonstrated TCE treatment induced a greater incidence of protein carbonyls compared with vehicle controls. Protein carbonyl formation in the ovary is consistent with TCE metabolism by the cytochrome P450 pathway. Oxidative damage following ovarian TCE metabolism or the presence of TCE metabolites may contribute to reduced oocyte fertilizability. In summary, these results indicate maturing oocytes are susceptible to very short in vivo exposures to TCE. PMID:17673192

  2. Convergence of sensory inputs upon projection neurons of somatosensory cortex: Vestibular, neck, head, and forelimb inputs

    Microsoft Academic Search

    P. Zarzecki; P. S. Blum; D. A. Bakker; D. Herman

    1983-01-01

    Cortico-cortical neurons and pyramidal tract (PT) neurons of the cat cerebral cortex were tested for convergent inputs from electrically stimulated vestibular, neck, head and forelimb nerves. Neurons were recorded within forelimb and vestibular projection regions of cortical area 3a. Consideration was given to both suprathreshold and subthreshold inputs. Neither vestibular, neck nor head inputs were detected in the forelimb region

  3. Arginine and Conjugated Linoleic Acid Reduce Fat Mass in Rats

    E-print Network

    Nall, Jennifer L.

    2010-10-12

    x LIST OF TABLES TABLE Page 1 Composition of diets fed to rats over a 5 wk period????????... 35 2 Fatty acid composition of diets fed to rats over 5 wk period?????.. 36 3 Weekly body weights, food intake, and alanine... x LIST OF TABLES TABLE Page 1 Composition of diets fed to rats over a 5 wk period????????... 35 2 Fatty acid composition of diets fed to rats over 5 wk period?????.. 36 3 Weekly body weights, food intake, and alanine...

  4. Electroacupuncture Reduces Hyperalgesia after Injections of Acidic Saline in Rats

    PubMed Central

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

    2014-01-01

    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. PMID:24772181

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

    PubMed

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

    2014-06-18

    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

  6. Oxyntomodulin reduces hydromineral transport through rat small intestine.

    PubMed

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

    1998-08-01

    Glicentin (GLIC) and oxyntomodulin (OXM) are released from the ileum and colon during digestion. Both hormones reduce fluid and proton secretion in the stomach. The luminal concentration of sodium and chloride underlying the nutrient absorption, the effect of OXM on electrolyte transport through the small intestine, was assessed in vivo using ligated loops and in vitro using Ussing chambers. In vivo, a zero transport state, estimated by the net water, chloride, and sodium fluxes, was observed when an 80 mM NaCl normoosmolar solution (274 mosm) was administered intraluminally. Active secretion was observed with hyperosmotic challenge (474 mosm). The amplitude of this active secretion increased 2.5- to 3-fold when an electrogenic challenge (NaCl 40 mM) was substituted to the hyperosmotic one. OXM (800 fmol/ml plasma) did not modify the basal transport in the duodenum or in the jejunum (t = 45 min). When active secretion was induced by the hyperosmotic challenge, OXM (200 fmol/ml plasma) had no effect on duodenal or jejunal transport (t = 50 min). When active secretion was induced by an electrogenic challenge, OXM (300 fmol/ml plasma) preferentially reduced the hydromineral transport in jejunum. In vitro, OXM also induced a reduction in the ion transport towards the jejunal lumen (EC50 = 20 pM), the amplitude of which depended upon the integrity of the tetrodotoxin-sensitive neurons. In conclusion, OXM was able to reduce the large secretion induced in rat jejunum in vivo by an electrogenic gradient. In vitro, the antisecretory effect of OXM was partly mediated by the neurons present in the intrajejunal wall. PMID:9724174

  7. Nonabsorbable antibiotics reduce bacterial and endotoxin translocation in hepatectomised rats.

    PubMed

    Kakkos, S K; Kirkilesis, J; Scopa, C D; Arvaniti, A; Alexandrides, T; Vagianos, C E

    1997-01-01

    There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics. PMID:9298382

  8. Antihyperlipidaemic, antihypertrophic, and reducing effects of zingerone on experimentally induced myocardial infarcted rats.

    PubMed

    Hemalatha, K L; Stanely Mainzen Prince, P

    2015-04-01

    The present study aims to evaluate the antihyperlipidaemic, antihypertrophic, and reducing effects of zingerone on isoproterenol-induced hyperlipidaemia and hypertrophy in rats. Rats were pretreated with zingerone (6 mg/kg body weight) daily for a period of 14 days and then induced myocardial infarction with isoproterenol (100 mg/kg body weight) on days 15 and 16. Isoproterenol increased serum creatine kinase and lactate dehydrogenase activities in the rats. Increased levels/concentrations of serum and heart cholesterol and triglycerides were observed in isoproterenol-induced myocardial infarcted rats. Isoproterenol also altered serum lipoproteins and the activity of liver 3-hydroxy-3-methyl glutaryl-coenzyme-A-reductase in the rats. The in vitro study revealed a very convincing reducing power of zingerone. Pretreatment with zingerone prevented hyperlipidaemia and cardiac hypertrophy, by virtue of its antihyperlipidaemic, antihypertrophic, and reducing properties in isoproterenol-induced myocardial infarcted rats. PMID:25558849

  9. Prenatal alcohol exposure (PAE) reduces the size of the forepaw representation in forepaw barrel subfield (FBS) cortex in neonatal rats: relationship between periphery and central representation.

    PubMed

    Margret, Cecilia P; Chappell, Tyson D; Li, Cheng X; Jan, Taha A; Matta, Shannon G; Elberger, Andrea J; Waters, Robert S

    2006-07-01

    Prenatal alcohol exposure (PAE) alters limb development that may lead to structural and functional abnormalities of the limb reported in children diagnosed with Fetal Alcohol Spectrum Disorder. To determine whether PAE alters the central representation of the forelimb we used the rodent barrel cortex as our model system where it was possible to visualize and quantitatively measure the size of the forepaw representation in the forepaw barrel subfield (FBS) in first somatosensory cortex. In the present study, we examined the effects of PAE on pattern and size of the forepaw and forepaw representation in FBS in neonatal rats at gestational day 32 that corresponds to postnatal day 9. Pregnant Sprague-Dawley rats were chronically intubated with binge doses of ethanol (6 g/kg) from gestational day 1 through gestational day 20. The offspring of the ethanol treated dams comprised the ethanol (EtOH) group. The effect of PAE on the EtOH group was compared with a nutritional-controlled pairfed (PF) group and a normal chowfed (CF) group. The ventral (glabrous) surface area of the forepaw digits, length of digit 2 through digit 5, and the corresponding glabrous forepaw digit representations in the FBS were measured and compared between treatment groups. In rats exposed to in utero alcohol, the sizes of the overall glabrous forepaw and forepaw digits were significantly reduced in EtOH pups compared to CF and PF pups; overall glabrous forepaw area was 11% smaller than CF controls. Glabrous digit lengths were also smaller in EtOH rats compared to CF controls and significantly smaller in digit 2 through digit 4. The glabrous digit representation in FBS was 18% smaller in the EtOH group when compared to the CF treatment. However, PAE did not produce malformations in the forepaw or alter the pattern of the forepaw representation in FBS; instead, PAE significantly reduced both body and brain weights compared to controls. Unexpectedly, little or no correlation was observed between the size of the glabrous forepaw compared to the size of the glabrous forepaw representation in the FBS for any of the treatment groups. The present findings of PAE-related alterations in sensory periphery and the central cortical representation may underlie deficits in sensorimotor integration reported among children with Fetal Alcohol Spectrum Disorder. PMID:16424976

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

    PubMed Central

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

    2014-01-01

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

  11. Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke

    PubMed Central

    Zai, Laila; Ferrari, Christina; Dice, Carlie; Subbaiah, Sathish; Havton, Leif A.; Coppola, Giovanni; Geschwind, Daniel; Irwin, Nina; Huebner, Eric; Strittmatter, Stephen M.; Benowitz, Larry I.

    2011-01-01

    Stroke is the leading cause of disability in much of the world, with few treatment options available. Following unilateral stroke in rats, inosine, a naturally occurring purine nucleoside, stimulates the growth of projections from the undamaged hemisphere into denervated areas of the spinal cord and improves skilled use of the impaired forelimb. Inosine augments neurons’ intrinsic growth potential by activating Mst3b, a component of the signal-transduction pathway through which trophic factors regulate axon outgrowth. The present study investigated whether inosine would complement the effects of treatments that promote plasticity through other mechanisms. Following unilateral stroke in the rat forelimb motor area, inosine combined with NEP1-40, a Nogo receptor antagonist, doubled the number of axon branches extending from neurons in the intact hemisphere into the denervated side of the spinal cord compared to either treatment alone and restored rats’ level of skilled reaching using the impaired forepaw to preoperative levels. Similar functional improvements were seen when inosine was combined with environmental enrichment (EE). The latter effect was associated with changes in gene expression in layer 5 pyramidal neurons of the undamaged cortex well beyond those seen with inosine or EE alone. Inosine is now in clinical trials for other indications, making it an attractive candidate for the treatment of stroke patients. PMID:21508223

  12. Dietary glutamine supplementation reduces plasma nitrate levels in rats

    Microsoft Academic Search

    A. P. J. Houdijk; J. J. Visser; E. R. Rijnsburger; T. Teerlink; P. A. M. van Leeuwen

    1998-01-01

    It was recently shown that L-glutamine inhibits vascular nitric oxide (NO) production in vitro. The present study investigated the effect of glutamine enriched enteral diets on in vivo NO production in the rat.Nitrate, the stable end-product of NO production, was measured in plasma and 24 h urine collectionsin glutamine supplemented rats (6.25%, 12.5% and 25% w\\/w) and compared to the

  13. Dietary cholesterol stimulates hepatic biosynthesis of triglyceride and reduces oxidation of fatty acids in the rat

    Microsoft Academic Search

    Thomas V. Fungwe; Lauren M. Cagen; George A. Cook; Henry G. Wilcox; Murray Heimberg

    Experiments were conducted in the intact rat and in the isolated, perfused rat liver to investigate the possibility that the increase in the concentration of hepatic triglyceride and in- crease in the secretion of the very low density lipoprotein (VLDL)-triglyceride (TG) resulting from addition of cholesterol to the diet are due to stimulation of synthesis of triglyceride, reduced fatty acid

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

    ERIC Educational Resources Information Center

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

    2013-01-01

    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…

  15. Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction

    E-print Network

    Quirk, Gregory J.

    Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction of conditioned fear. Less is known, however, about their role in fear expression and extinction. The -receptor in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures

  16. Topiramate Reduces Energy and Fat Gains in Lean (Fa\\/?) and Obese (fa\\/fa) Zucker Rats

    Microsoft Academic Search

    Frédéric Picard; Yves Deshaies; Josée Lalonde; Pierre Samson; Denis Richard

    2000-01-01

    Objective: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats.Research Methods and Procedures: A 2 × 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa\\/?; obese, fa\\/fa) were each divided

  17. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    SciTech Connect

    Winocour, P.D.; Colwell, J.A.

    1985-05-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

  18. Sodium Salicylate Reduced Insulin Resistance in the Retina of a Type 2 Diabetic Rat Model

    PubMed Central

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J.; Steinle, Jena J.

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNF? and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNF? and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models. PMID:25874611

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

    E-print Network

    D'Août, Kristiaan

    & Wood, 2011). How- ever, forelimb muscle architecture (muscle mass, fascicle length and physiological ilia, broad, shallow trunks, dorsally placed scapulae, and shoulder joints otherwise adapted for highly

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

    PubMed

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

    2013-11-01

    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

  1. Doramectin reduces sexual behavior and penile erection in male rats.

    PubMed

    Ferri, R; Todon E Silva, A F S; Cabral, D; Moreira, N; Spinosa, H S; Bernardi, M M

    2013-01-01

    Doramectin (DOR) is an antiparasitic drug that is widely used in domestic animals. In mammals, DOR acts as a ?-aminobutyric acid receptor agonist. This neurotransmitter plays an important role in the regulation of sexual behavior. The present study investigated the effects of two medically relevant doses of DOR on sexual behavior in male rats. We also examined whether previous sexual experience modulates responses to DOR. General activity was first observed in an open field 24, 48, and 72 h after administration of 0.1 and 0.3 mg/kg DOR to determine the dose and time effects of the drug. Apomorphine-induced penile erection and sexual behavior in inexperienced male rats were then analyzed. The effects of previous sexual experience on subsequent sexual behavior in DOR-treated rats (0.3 mg/kg, 24 h prior to the test) were also assessed. The standard therapeutic dose (0.2 mg/kg) did not modify general activity or penile erection. A slightly concentrated dose of 0.3 mg/kg, which is still within the therapeutic range, decreased apomorphine-induced penile erection, whereas 0.2 mg/kg did not modify this behavior. Compared with controls, sexual behavior in inexperienced male rats was impaired after 0.3 mg/kg DOR. Previous sexual experience had little impact on the effects of 0.3 mg/kg DOR. In conclusion, the 0.2 mg/kg dose of DOR did not affect motor behavior or apomorphine-induced penile erection. At a more slightly higher dose level, the appetitive and consummatory phases of sexual behavior in inexperienced male rats were impaired. Previous sexual experience was unable to reverse this sexual impairment, suggesting that previous sexual experience does not exert a positive effect in attenuating sexual impairment produced by DOR treatment. PMID:23899514

  2. An alpha-synuclein AAV gene silencing vector ameliorates a behavioral deficit in a rat model of Parkinson’s disease, but displays toxicity in dopamine neurons

    PubMed Central

    Khodr, Christina E.; Sapru, Mohan K.; Pedapati, Jyothi; Han, Ye; West, Neva C.; Kells, Adrian P.; Bankiewicz, Krystof S.; Bohn, Martha C.

    2011-01-01

    Effects of silencing ectopically expressed hSNCA in rat substantia nigra (SN) were examined as a novel therapeutic approach to Parkinson’s disease (PD). AAV-hSNCA with or without an AAV harboring a short-hairpin (sh)RNA targeting hSNCA or luciferase was injected into one SN. At 9wks, hSNCA-expressing rats had reduced SN dopamine (DA) neurons and exhibited a forelimb deficit. AAV-shRNA-SNCA silenced hSNCA and protected against the forelimb deficit. However, AAV-shRNA-SNCA also led to DA neuron loss suggesting undesirable effects of chronic shRNA expression. Effects on nigrostriatal-projecting neurons were examined using a retrograde tract tracer. Loss of striatal-projecting DA neurons was evident in the vector injection site, whereas DA neurons outside this site were lost in hSNCA-expressing rats, but not in hSNCA-silenced rats. These observations suggest that high levels of shRNA-SNCA were toxic to DA neurons, while neighboring neurons exposed to lower levels were protected by hSNCA gene silencing. Also, data collected on DA levels suggest that neurons other than or in addition to nigrostriatal DA neurons contributed to protection of forelimb use. Our observations suggest that while hSNCA gene silencing in DA neurons holds promise as a novel PD therapy, further development of silencing technology is required. PMID:21565333

  3. Effect of Amniotic Membrane to Reduce Postlaminectomy Epidural Adhesion on a Rat Model

    PubMed Central

    Choi, Hyu Jin; Kim, Kyoung Beom

    2011-01-01

    Objective Epidural fibrosis and adhesion are the main reasons for post-laminectomy sustained pain and functional disability. In this study, the authors investigate the effect of irradiated freeze-dried human amniotic membrane on reducing epidural adhesion after laminectomy on a rat model. Methods A total of 20 rats were divided into two groups. The group A did not receive human amniotic membrane implantation after laminectomy and group B underwent human amniotic membrane implantation after laminectomy. Gross and microscopic findings were evaluated and compared at postoperative 1, 3 and 8 weeks. Results The amount of scar tissue and tenacity were reduced grossly in group of rats with human amniotic membrane implantation (group B). On a microscopic evaluation, there were less inflammatory cell infiltration and fibroblast proliferation in group B. Conclusion This experimental study shows that implantation of irradiated freeze-dried human amniotic membrane reduce epidural fibrosis and adhesion after spinal laminectomy in a rat model. PMID:21887388

  4. Contralesional Axonal Remodeling of the Corticospinal System in Adult Rats After Stroke and Bone Marrow Stromal Cell Treatment

    PubMed Central

    Liu, Zhongwu; Li, Yi; Zhang, Xueguo; Savant-Bhonsale, Smita; Chopp, Michael

    2008-01-01

    Background and Purpose Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Methods Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. Results In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05). Conclusions Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery. PMID:18617661

  5. Coordination strategies for limb forces during weight-bearing locomotion in normal rats, and in rats spinalized as neonates

    PubMed Central

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

    2010-01-01

    Some rats spinally transected as neonates (ST rats) achieve weight-supporting independent locomotion. The mechanisms of coordinated hindlimb weight support in such rats are not well understood. To examine these in such ST rats and normal rats, rats with better than 60% of weight supported steps on a treadmill as adults were trained to cross an instrumented runway. Ground reaction forces, coordination of hindlimb and forelimb forces and the motions of the center of pressure were assessed. Normal rats crossed the runway with a diagonal trot. On average hindlimbs bore about 80% of the vertical load carried by forelimbs, although this varied. Forelimbs and hindlimb acted synergistically to generate decelerative and propulsive rostrocaudal forces, which averaged 15% of body weight with maximums of 50% . Lateral forces were very small (<8% of body weight). Center of pressure progressed in jumps along a straight line with mean lateral deviations <1 cm. ST rats hindlimbs bore about 60% of the vertical load of forelimbs, significantly less compared to intact (p<0.05). ST rats showed similar mean rostrocaudal forces, but with significantly larger maximum fluctuations of up to 80% of body weight (p<0.05). Joint force-plate recordings showed forelimbs and hindlimb rostrocaudal forces in ST rats were opposing and significantly different from intact rats (p<0.05). Lateral forces were ~20% of body weight and significantly larger than in normal rats (p<0.05). Center of pressure zig-zagged, with mean lateral deviations of ~ 2cm and a significantly larger range (p<0.05). The haunches were also observed to roll more than normal rats. The locomotor strategy of injured rats using limbs in opposition was presumably less efficient but their complex gait was statically stable. Because forelimbs and hindlimbs acted in opposition, the trunk was held compressed. Force coordination was likely managed largely by the voluntary control in forelimbs and trunk. PMID:18612631

  6. Calculation of Joint Reaction Forces in the Equine Distal Forelimb during Walking and Trotting

    Microsoft Academic Search

    Jonathan S. Merritt; Helen M. S. Davies; Colin Burvill; Marcus G. Pandy

    2007-01-01

    Forces exerted at the joints of the equine distal forelimb play a major role in common injuries of the region. In this study, a two-dimensional musculoskeletal model was developed to calculate the reaction forces at the joints of the distal forelimb from measured kinematic and kinetic data during walking and trotting. The reaction forces due to muscle- tendon wrapping around

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

    ERIC Educational Resources Information Center

    Lee, Scott A.; Thomas, Joshua D.

    2014-01-01

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

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

    Microsoft Academic Search

    Jeff Biernaskie; Dale Corbett

    2001-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    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. PMID:24155423

  11. Ischemic preconditioning reduces intestinal epithelial apoptosis in rats.

    PubMed

    Cinel, Ismail; Avlan, Dincer; Cinel, Leyla; Polat, Gurbuz; Atici, Sebnem; Mavioglu, Ilhan; Serinol, Hasan; Aksoyek, Selim; Oral, Ugur

    2003-06-01

    Recent experimental studies have described protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We hypothesize that to reach a new point of view on the effect of IPC in intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must first be clarified. The present study was undertaken to investigate the role of IPC on intestinal apoptosis and probable contributions of bcl-2 expression to this process. We also investigated the effect of intestinal IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized into four groups each consisting of 11 rats: sham-operated control, I/R group (30 min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary artery occlusion prior before an ischemic insult of 30 min), and IPC alone group (10 min of preconditioning). Twenty-four hours later, ileum samples were obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/- 18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/- 13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was significantly lower in IPC-I/R group than that of I/R group, and these findings were further supported by DNA laddering and M30 findings. Diminished bcl-2 expression observed in the ileal specimens of I/R group was prevented by IPC. Our results indicate that IPC may provide a protective effect on ileal epithelium and that this effect is probably the result of a significant increase in the expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help preserving the vitality of intestinal structures that have a critical function, cessation of which often leads to multiorgan dysfunction syndrome. PMID:12785017

  12. Nitric oxide synthase inhibitors reduce sarcomere addition in rat skeletal muscle.

    PubMed

    Koh, T J; Tidball, J G

    1999-08-15

    1. Mechanical stimuli are thought to modulate the number of sarcomeres in series (sarcomere number) in skeletal muscle fibres. However, the mechanisms by which muscle cells transduce mechanical signals into serial sarcomere addition have not been explored. In this study, we test the hypothesis that nitric oxide positively modulates sarcomere addition. 2. The soleus muscle was cast-immobilized in a shortened position in 3-week-old female Wistar rats. After 4 weeks, the casts were removed, creating a period of rapid sarcomere addition. During the remobilization period, nitric oxide synthase (NOS) inhibitors or substrate were administered. 3. Rats treated with the non-isoform-specific NOS inhibitor L-nitro-arginine methyl ester during 3 weeks of remobilization had smaller soleus sarcomere numbers than control rats. Rats treated with 1-(2-trifluoromethyl-phenyl)-imidazole, which has greater specificity for the neuronal isoform than for the endothelial isoform of NOS, also had smaller soleus sarcomere numbers than control rats. These results suggest that inhibition of the neuronal isoform of NOS reduces sarcomere addition during remobilization. 4. Rats treated with L-arginine, the substrate for NOS, during 1 week of remobilization had soleus sarcomere numbers for the immobilized-remobilized muscle which were closer to that for the contralateral, non-immobilized muscle than did rats that were not treated with L-arginine. 5. These results support the hypothesis that nitric oxide derived from the neuronal isoform of NOS positively modulates sarcomere addition. PMID:10432349

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

    PubMed Central

    2014-01-01

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

  14. Morphological integration in the forelimb of musteloid carnivorans.

    PubMed

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

    2014-07-01

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

  15. Neuronal activity of the prefrontal cortex is reduced in rats selectively bred for deficient sensorimotor gating.

    PubMed

    Alam, Mesbah; Angelov, Svilen; Stemmler, Meike; von Wrangel, Christof; Krauss, Joachim K; Schwabe, Kerstin

    2015-01-01

    Rats selectively bred for deficient prepulse inhibition (PPI), an operant measure of sensorimotor gating in which a weak prepulse stimulus attenuates the response to a subsequent startling stimulus, may be used to study certain pathophysiological mechanisms and therapeutic strategies for neuropsychiatric disorders with abnormalities in information processing, such as schizophrenia and Tourette's syndrome (TS). Little is known about neuronal activity in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), which are involved in the modulation of PPI. Here, we examined neuronal activity in these structures, and also in the entopeduncular nucleus (EPN), since lesions of this region alleviate the PPI deficit. Male rats with breeding-induced high and low expression of PPI (n=7, each) were anesthetized with urethane (1.4 mg/kg). Single-unit activity and local field potentials were recorded in the mPFC, the NAC and in the EPN. In the mPFC discharge rate, measures of irregularity and burst activity were significantly reduced in PPI low compared to PPI high rats (P<0.05), while analysis in the NAC showed approximately inverse behavior. In the EPN no difference between groups was found. Additionally, the oscillatory theta band activity (4-8 Hz) was enhanced and the beta band (13-30 Hz) and gamma band (30-100 Hz) activity was reduced in the NAC in PPI low rats. Reduced neuronal activity in the mPFC and enhanced activity in the NAC of PPI low rats, together with altered oscillatory behavior are clearly associated with reduced PPI. PPI low rats may thus be used to study the pathophysiology and therapeutic strategies for neuropsychiatric disorders accompanied by deficient sensorimotor gating. PMID:25220677

  16. The Mechanism by Which Ischemic Postconditioning Reduces Reperfusion Arrhythmias in Rats Remains Elusive

    Microsoft Academic Search

    Joan Dow; Anil Bhandari; Robert A. Kloner

    2009-01-01

    We have observed that ischemic postconditioning markedly reduces reperfusion-induced ventricular arrhythmias, but whether the mechanism is related to previously described pathways of preconditioning or postconditioning for infarct size reduction is unknown. The purpose of this study was to determine whether known pathways were involved in postconditioning's protective effect on arrhythmias.Anesthetized female rats were subjected to 5 minutes of proximal coronary

  17. Energy restriction reduces metabolic rate in adult male Fisher-344 rats.

    PubMed

    Gonzales-Pacheco, D M; Buss, W C; Koehler, K M; Woodside, W F; Alpert, S S

    1993-01-01

    Energy restriction, without malnutrition, prolongs the maximum life span of laboratory rodents. A reduction in metabolic rate has been proposed as a potential mechanism for increased longevity. The present study examines changes in metabolic rate of adult rats after a 6-wk period of energy restriction. Two groups (n = 6) of 6-mo-old male Fisher-344 rats were studied. Restricted rats were pair-fed a diet equivalent in vitamins and minerals but restricted to 60% of energy consumed by rats eating ad libitum. Average and basal metabolic rates were measured by direct calorimetry over a 24-h period without food. Fat mass and lean body mass were determined by NMR spectroscopy. After 6 wk of restriction, when expressed per kilogram of lean body mass the average metabolic rate was reduced by 14% and basal metabolic rate by 12% compared with the ad libitum diet rats (P < or = 0.01). Reduction of metabolic rate did not seem to be a transient effect of chronic energy restriction in mature rats. PMID:8421235

  18. Naloxone reduces diuretic responses induced by water, alcohol or congenital lack of vasopressin in rats.

    PubMed Central

    Guiol, C.; Montastruc, J. L.; Montastruc, P.

    1984-01-01

    The effects of naloxone (2 and 10 mg kg-1 s.c.) were compared in several kinds of experimental polyuria: alcohol- or water-loaded rats and Brattleboro rats (i.e. animals with congenital lack of vasopressin). In normal rats, both water and alcohol increased urine flow and decreased urinary osmolality. Alcohol induced a more marked diuretic response than water. In normally hydrated rats, naloxone (2 and 10 mg kg-1 s.c.) failed to modify urine flow, urinary osmolality, Na+ and K+ urinary excretion, and urine creatinine concentration. The two doses of naloxone decreased urine flow and increased osmolality in both water- and alcohol-loaded rats. In Brattleboro rats, naloxone (10 mg kg-1 s.c.) reduced urine flow and urinary creatine whereas the low dose (2 mg kg-1 s.c.) was without effect. Since it is well known that the mechanism of water- or alcohol-induced diuresis is an inhibition of vasopressin release, the present results suggest that naloxone could prevent this inhibition. They indicate that endogenous opioid peptides may exert an inhibitory control on vasopressin release. PMID:6704587

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

    PubMed

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

    2009-09-01

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

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

    PubMed

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

    2014-02-28

    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

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

    PubMed Central

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

    2014-01-01

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

  2. Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure.

    PubMed

    Zhou, Xiaoyan; Zhang, Zuo; Shin, Myung Kyun; Horwitz, Sarah Beth; Levorse, John M; Zhu, Lei; Sharif-Rodriguez, Wanda; Streltsov, Denis Y; Dajee, Maya; Hernandez, Melba; Pan, Yi; Urosevic-Price, Olga; Wang, Li; Forrest, Gail; Szeto, Daphne; Zhu, Yonghua; Cui, Yan; Michael, Bindhu; Balogh, Leslie Ann; Welling, Paul A; Wade, James B; Roy, Sophie; Sullivan, Kathleen A

    2013-08-01

    The renal outer medullary potassium channel (ROMK, KCNJ1) mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK(-/-) pups recapitulated features identified in the ROMK null mice. The ROMK(+/-) rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK(+/+) littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation. PMID:23753405

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

    PubMed

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

    2013-03-01

    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

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

    PubMed Central

    Milliken, Garrett W.; Plautz, Erik J.

    2013-01-01

    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

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

    PubMed Central

    Schallert, Timothy; Schmidt, Christine E.

    2013-01-01

    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. PMID:24084700

  6. Reduced presynaptic dopamine receptor density after chronic antidepressant treatment in rats.

    PubMed

    Lee, T; Tang, S W

    1982-08-01

    Chronic administration of desipramine and nomifensine to rats reduced the number of presynaptic dopamine receptors as labeled by 3H-dopamine in rat striatal tissues, with no change in receptor affinity. This change can only be brought about by continuous daily treatment with antidepressants for a duration of at least 21 days or longer. All antidepressants did not displace 3H-spiperone or 3H-dopamine at low concentrations in vitro, suggesting that the agents may not act on the dopamine receptors directly. A possible interaction between neurotransmitters in the central nervous system for the overall therapeutic effect of antidepressant drugs was proposed. PMID:6957896

  7. Efficacy of AdiDetox™ in reducing the toxicity of fumonisin B1 in rats.

    PubMed

    Denli, Muzaffer; Blandon, Juan C; Salado, Silvia; Guynot, Maria E; Casas, Josefina; Pérez, Jose F

    2015-04-01

    The objective of this study is to evaluate the efficacy of a new mycotoxin inactivator (AdiDetox™) in reducing the toxic effects of fumonisin B1 (FB1) in the diet of rats. Sixty-four male Sprague-Dawley growing rats (125?g?±?1?g BW) were assigned to eight dietary treatments for seven days. The experiment had a 2?×?4 factorial arrangement with two levels of FB1 (0?mg and 15?mg of FB1/kg feed) and four levels of AdiDetox™ (0?g, 1?g, 2?g and 5?g /kg feed) in the diet. No significant differences were observed in the growth performance among treatments (P?>?0.05), though low levels of sphingosine (So) and sphinganine (Sa) were detected in the liver. However, So and Sa and the Sa/So ratio in kidneys were higher in rats receiving the FB1 diets (P?reduced the toxic effects of FB1, leading to a significant decrease in the Sa content and in the Sa/So ratio in kidneys. In conclusion, the results suggest that AdiDetox™ can effectively reduce toxicity of FB1 in growing rats. PMID:25660482

  8. Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

    PubMed

    Rasmussen, Erin B; Hillman, Conrad

    2011-12-01

    Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy. PMID:21707193

  9. Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

    PubMed Central

    López-Dolado, Elisa; Lucas-Osma, Ana M.

    2013-01-01

    Abstract 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

  10. Force and moment-generating capacities of muscles in the distal forelimb of the horse

    Microsoft Academic Search

    Nicholas A. T. Brown; Marcus G. Pandy; Christopher E. Kawcak; C. Wayne McIlwraith

    2003-01-01

    A detailed musculoskeletal model of the distal equine forelimb was developed to study the influence of muscu- loskeletal geometry (i.e. muscle paths) and muscle physiology (i.e. force-length properties) on the force- and moment-generating capacities of muscles crossing the carpal and metacarpophalangeal joints. The distal forelimb skeleton was represented as a five degree-of-freedom kinematic linkage comprised of eight bones (humerus, radius

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

    PubMed Central

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

    2001-01-01

    BACKGROUND AND AIMS—Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis.?METHODS—Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS).?RESULTS—Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed colon. Staining of sections of colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of colon injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the colon.?CONCLUSION—Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease.???Keywords: calpain; calpain inhibitor I; cyclooxygenase; nitric oxide; inflammatory bowel disease; rat PMID:11247891

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. High fiber probiotic fermented mare's milk reduces the toxic effects of mercury in rats

    PubMed Central

    Abdel-Salam, Ahmed M.; Al-Dekheil, Ali; Babkr, Ali; Farahna, Mohammed; Mousa, Hassan M.

    2010-01-01

    Background: Since the advent of the Industrial Revolution in the late 19th century, we have all been unfortunately exposed to an increasingly toxic and polluted world. Among the most dangerous of these pollutants is mercury, which is considered to be the most toxic non-radioactive heavy metal. Fermented foods may help cleanse the body of heavy metals. Fermentation breaks down the nutrients in foods by the action of beneficial microorganisms and creates natural chelators that are available to bind toxins and remove them from the body. Aims: The current study was designed to determine the impact of feeding a high fiber probiotic fermented mare's milk on the biological effects of mercury toxicity in rat model. Methods and Materials: The high fiber fermented mare's milk containing probiotics was prepared and its sensory properties, chemical composition, and antioxidant activity were determined. A rat model of mercury toxicity was used. The effect of feeding the high fiber probiotic fermented mare's milk to rats, along with mercury ingestion, was determined by the analysis of several biochemical markers in serum and histopathological examinations of brain and kidney. Results: The high fiber fermented mare's milk containing probiotics was found to be acceptable by all test panels and volunteers. Mercury ingestion was found to cause biochemical and histopathological alterations in rat serum and tissues. The mercury-treated rats showed a decrease in body weight and an increase in kidney weight. Sera of the mercury treated rats showed alterations in biochemical parameters, and histopathological changes in brain and kidney. However, the rats fed high fiber fermented mare`s milk along with mercury ingestion showed improved histopathology of kidney and brain, and there was restoration of the biochemical parameters in serum to almost normal values. Conclusions: Feeding high fiber fermented mare`s milk may reduce the toxic effects of mercury. PMID:22558569

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

    PubMed Central

    Wang, Lijun; Li, Juan; Li, Dajun

    2015-01-01

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

  16. COX-2-derived prostanoids and oxidative stress additionally reduce endothelium-mediated relaxation in old type 2 diabetic rats.

    PubMed

    Vessières, Emilie; Guihot, Anne-Laure; Toutain, Bertrand; Maquigneau, Maud; Fassot, Céline; Loufrani, Laurent; Henrion, Daniel

    2013-01-01

    Endothelial dysfunction in resistance arteries alters end organ perfusion in type 2 diabetes. Superoxides and cyclooxygenase-2 (COX-2) derivatives have been shown separately to alter endothelium-mediated relaxation in aging and diabetes but their role in the alteration of vascular tone in old diabetic subjects is not clear, especially in resistance arteries. Consequently, we investigated the role of superoxide and COX-2-derivatives on endothelium-dependent relaxation in 3 and 12 month-old Zucker diabetic fatty (ZDF) and lean (LZ) rats. Mesenteric resistance arteries were isolated and vascular tone was investigated using wire-myography. Endothelium (acetylcholine)-dependent relaxation was lower in ZDF than in LZ rats (60 versus 84% maximal relaxation in young rats and 41 versus 69% in old rats). Blocking NO production with L-NAME was less efficient in old than in young rats. L-NAME had no effect in old ZDF rats although eNOS expression level in old ZDF rats was similar to that in old LZ rats. Superoxide level and NADPH-oxidase subunits (p67phox and gp91phox) expression level were greater in ZDF than in LZ rats and were further increased by aging in ZDF rats. In young ZDF rats reducing superoxide level with tempol restored acetylcholine-dependent relaxation to the level of LZ rats. In old ZDF rats tempol improved acetylcholine-dependent relaxation without increasing it to the level of LZ rats. COX-2 (immunolabelling and Western-blot) was present in arteries of ZDF rats and absent in LZ rats. In old ZDF rats arterial COX-2 level was higher than in young ZDF rats. COX-2 blockade with NS398 restored in part acetylcholine-dependent relaxation in arteries of old ZDF rats and the combination of tempol and NS398 fully restored relaxation in control (LZ rats) level. Accordingly, superoxide production and COX-2 derivatives together reduced endothelium-dependent relaxation in old ZDF rats whereas superoxides alone attenuated relaxation in young ZDF or old LZ rats. PMID:23874545

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

    PubMed Central

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

    2013-01-01

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

  18. 5?-Reduced Neurosteroids Sex-Dependently Reverse Central Prenatal Programming of Neuroendocrine Stress Responses in Rats

    PubMed Central

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

    2015-01-01

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

  19. Active immunization against GnRH reduces the synthesis of GnRH in male rats.

    PubMed

    Han, Xing-fa; Cao, Xiao-han; Tang, Jing; Du, Xiao-gang; Zeng, Xian-yin

    2013-12-01

    We sought to determine the effects of active anti-GnRH immunization on GnRH synthesis in the hypothalamus. Adult male rats (n = 36) were randomly and equally allocated into three groups: Control (no treatment), surgically castrated, or immunized against 50 ?g D-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin in Specol adjuvant at 12 week of age (with a booster 8 week later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (20 week). Compared with intact controls, immunocastration reduced (P < 0.05) serum concentrations of testosterone, LH, and FSH, and GnRH content in the median eminence, reduced the weight of the hypohysis (P < 0.01), and induced testicular atrophy (suppression of spermatogenesis). Furthermore, mRNA expression of GnRH in the hypothalamus, GnRH receptor, LH-? and FSH-? in the pituitary, LH receptor and FSH receptor in the testes, and genes in sex steroid feedback loops (androgen receptor [AR], kisspeptin encoded gene (Kiss-1), and kisspeptin receptor (GPR54) in the hypothalamus were decreased in immunocastrated rats compared with intact controls (P < 0.05). Similarly, surgical castration reduced GnRH in the median eminence as well as mRNA expression of GnRH, AR, Kiss-1, and GPR54 in the hypothalamus (P < 0.05). We concluded that anti-GnRH immunization in adult rats reduced synthesis of hypothalamic GnRH by decreasing androgen-AR-Kisspeptin-GPR54 signaling pathways, and caused dysfunction of the pituitary-testicular axis, thereby suppressing spermatogenesis, resulting in testicular atrophy. PMID:24084232

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

    Microsoft Academic Search

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

    2011-01-01

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

  1. Acute methylphenidate treatments reduce sucrose intake in restricted-fed bingeing rats

    Microsoft Academic Search

    N. T. Bello; A. Hajnal

    2006-01-01

    Recent evidence suggests that methylphenidate HCl may be effective at limiting the frequency and the amount of binge eating. The present study investigated if daily treatments with methylphenidate reduced the bingeing-like behavior observed in restricted-fed adult male rats. Three groups (n=6) received peripheral injections of methylphenidate in doses of 1.5 or 0.75mg\\/kg\\/day, or saline, 3 days prior and 7 days

  2. Methysergide and metergoline reduce morphine analgesia with no effect on the development of tolerance in rats

    Microsoft Academic Search

    S. Romandini; R. Samanin

    1983-01-01

    A single subcutaneous injection of 5 mg\\/kg metergoline or 10 mg\\/kg methysergide, two serotonin antagonists, or 1 mg\\/kg naloxone, significantly reduced the effect of a subcutaneous dose of 3 mg\\/kg morphine in the tail immersion test in rats. The same drugs and doses were administered concurrently with 10 mg\\/kg morphine twice daily for 3 days and nociceptive responses were measured

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

    Microsoft Academic Search

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

    2003-01-01

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

  4. Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis

    Microsoft Academic Search

    Laszlo Wagner; Amy Riggleman; Aaron Erdely; William Couser; Chris Baylis

    2002-01-01

    Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis.BackgroundAnimal studies with systemic nitric oxide synthase (NOS) inhibition and renal ablation, suggest that NO deficiency is both a cause and a consequence of chronic renal disease (CRD).MethodsThis study examined a glomerulonephritis (GN) model of CRD to determine if NO is deficient. In addition to measuring indices

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

    Microsoft Academic Search

    Francesco Leri; Lindsay H. Burns

    2005-01-01

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

  6. 5?-Reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in rats.

    PubMed

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

    2015-01-14

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

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

    PubMed

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

    2013-01-01

    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

  8. Reduced expression of folate transporters in kidney of a rat model of folate oversupplementation.

    PubMed

    Thakur, Shilpa; Thakur, Som Dev; Wani, Nissar Ahmad; Kaur, Jyotdeep

    2014-01-01

    Folic acid is the key one-carbon donor required for de novo nucleotide and methionine synthesis. Its deficiency is associated with megaloblastic anemia, cancer and various complications of pregnancy. However, its supplementation results in reduction of neural tube defects and prevention of several types of cancer. The intake of folic acid from fortified food together with the use of nutritional supplements creates a state of folate oversupplementation. Fortification of foods is occurring worldwide with little knowledge of the potential safety and physiologic consequences of intake of such high doses of folic acid. So, we planned to examine the effects of acute and chronic folate oversupplementation on the physiology of renal folate transport in rats. Male Wistar rats were procured and divided into two groups. Rats in group I were given semisynthetic diets containing 2 mg folic acid/kg diet (control) and those in group II were given folate-oversupplemented rat diet, i.e., 20 mg folic acid/kg diet (oversupplemented). Six animals from group I and group II received the treatment for 10 days (acute treatment) and remaining six for 60 days (chronic treatment). In acute folate-oversupplemented rats, 5-[(14)C]-methyltetrahydrofolate uptake was found to be significantly reduced, as compared to chronic folate-oversupplemented and control rats. This reduction in uptake was associated with a significant decrease in the mRNA and protein levels of the folate transporters. Results of the present investigation showed that acute oversupplementation led to a specific and significant down-regulation of renal folate uptake process mediated via transcriptional and translational regulatory mechanism(s). PMID:24306960

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

    PubMed Central

    Granzotto, Natalli; Ramos, André

    2013-01-01

    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. PMID:24386249

  10. Enhanced depletion of lens reduced glutathione Adriamycin in riboflavin-deficient rats.

    PubMed

    Dutta, P; Rivlin, R S; Pinto, J

    1990-09-01

    The anticancer drug Adriamycin has photosensitizing properties which potentially may be detrimental to lens tissue. Since reduced glutathione (GSH) serves to protect lens from photo-oxidative stress and dietary riboflavin is required by glutathione reductase to regenerate GSH, we investigated whether Adriamycin intensifies the depletion of GSH levels in rat lens during dietary riboflavin deficiency. Three-week-old rats were divided into two groups. One group was fed a diet deficient in riboflavin (less than 1 ppm) and the other group was pair-fed a control diet containing adequate riboflavin (8.5 ppm). After 6-12 weeks of dietary treatment, half the animals in each dietary group received Adriamycin (8 mg/kg/day) intraperitoneally for 3 days. After killing the rats, lenses were removed, and GSH content and glutathione reductase activity were measured in freshly prepared homogenates. To determine the extent of systemic oxidative stress and the degree of riboflavin deficiency, glucose-6-phosphate dehydrogenase and glutathione reductase activities, respectively, were measured in erythrocytes. In lens of rats fed the riboflavin-sufficient diet, treatment with Adriamycin did not diminish GSH content or alter glutathione reductase activity. In confirmation of reports by others, lenses of animals fed the riboflavin-deficient diet had diminished GSH levels, lower basal glutathione reductase activity, and elevated glutathione reductase activity coefficients compared to those of animals pair-fed the control diet. The present study shows that in riboflavin-deficient rats, Adriamycin exacerbated the depletion of GSH but did not reduce further glutathione reductase activity. The implications of these findings are that nutritional deficiencies, in particular riboflavin deprivation, may pose a potential risk to lenticular tissue following Adriamycin treatment. PMID:2390107

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

    PubMed

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

    2012-09-10

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

  12. Reduced hippocampal cell differentiation in the subgranular zone of the dentate gyrus in a rat model of type II diabetes.

    PubMed

    Hwang, In Koo; Yi, Sun Shin; Kim, Yo Na; Kim, Il Yong; Lee, In Se; Yoon, Yeo Sung; Seong, Je Kyung

    2008-03-01

    It has recently been reported that diabetes mellitus is strongly associated with neurodegenerative and functional disorders of the central nervous system. In the present study, we investigated the changes in proliferating neurons in the dentate gyrus of type II diabetic rats using doublecortin (DCX), a marker of progenitors differentiating into neurons. At 4 weeks after birth, there were no differences in the blood glucose levels of Zucker diabetic fatty (ZDF) rats or Zucker lean control (ZLC) rats. DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in both the ZDF and ZLC rats; however, DCX immunoreactivity was higher in the ZLC rats than in the ZDF rats. At 12 weeks after birth, the blood glucose level was significantly increased by 400 mg/dl in the ZDF rats, but the blood glucose level in the ZLC rats was only slightly increased by 152.3 mg/dl. DCX immunoreactivity was significantly decreased in 12-week-old rats in comparison to 4-week-old rats. Some DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in the ZLC rats. However, only a few DCX-immunoreactive neurons were observed in the ZDF rats, and the DCX-immunoreactive neurons in the ZDF rats did not show fully developed processes. These results suggest that DCX-immunoreactive neurons were significantly decreased in an age-dependent manner and that DCX-immunoreactive neurons were also reduced in diabetic rats. In addition, the reduction in DCX-immunoreactive neurons in age matched rats may be associated with type II diabetes. PMID:17712629

  13. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    PubMed Central

    Girgih, Abraham T.; Alashi, Adeola M.; He, Rong; Malomo, Sunday A.; Raj, Pema; Netticadan, Thomas; Aluko, Rotimi E.

    2014-01-01

    This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR). Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old) SHRs were divided into three groups (8 rats/group) and fed diets that contained 0.0%, 0.5% or 1.0% (w/w) HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD), catalase (CAT) and total peroxides (TPx) levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05) increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity. PMID:25493943

  14. A Magnesium Based Phosphate Binder Reduces Vascular Calcification without Affecting Bone in Chronic Renal Failure Rats

    PubMed Central

    Neven, Ellen; De Schutter, Tineke M.; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C.; Behets, Geert J.

    2014-01-01

    The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover. PMID:25229549

  15. Comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni, and the scansorial fox squirrel, Sciurus niger.

    PubMed

    Stalheim-Smith, A

    1984-04-01

    A comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni , and the scansorial tree squirrel, Sciurus niger, was focused on the musculoskeletal design for digging in the former and climbing in the latter. Based on lever arm mechanics, it was expected that the forelimb of the prairie dog would show features appropriate to the production of relatively large forces and that of the fox squirrel to relatively great velocity. Force and lever arm measurements were made of select forelimb muscles at the shoulder, elbow, and wrist joints for a series of angles in both species. Contraction time and fatigue indexes were determined for the same forelimb muscles. Contrary to expectation, in the few cases in which significant (P less than .05) differences were found, the forces, lever arms, and torques (force times its lever arm) were greater in the smaller fox squirrel. The observed variation in the torques produced fits the demands on the forelimb during climbing and digging as estimated from films. Several forelimb muscles of the fox squirrel show significantly higher mean contraction times than do the homologous muscles of the prairie dog. There were no significant differences between the two species in the fatigability of the selected forelimb muscles, although the mean fatigue index was always higher (less fatigable muscle) in the prairie dog. Similarities in the forelimbs of these two sciurids suggest that only minor modifications may have been required of the ancestral forelimb in order for descendent forms to operate successfully as climbers and diggers . PMID:6726818

  16. The Serotonin Reuptake Inhibitor Fluoxetine Reduces Sex Steroid-Related Aggression in Female Rats: An Animal Model of Premenstrual Irritability?

    Microsoft Academic Search

    Hoi-Por Ho; Marie Olsson; M Pharm; Lars Westberg; Jonas Melke; Elias Eriksson

    2001-01-01

    The aggressive behavior displayed by some (but not all) female Wistar rats when an unfamiliar rat is being introduced into their home cage (the resident intruder paradigm) was found to be higher in non-receptive phases (metestrus, diestrus) than in the receptive phases (proestrus, estrus) of the estrus cycle, and effectively reduced by ovariectomy. When removal of the ovaries was followed

  17. Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats

    Microsoft Academic Search

    Jason E. Gallate; Paul E. Mallet; Iain S. McGregor

    2004-01-01

    Rationale Opioid and cannabinoid CB 1 receptor antagonists reduce the motivation to consume alcohol when taken individually but their effectiveness in combination is not yet known. Objective The effects of naloxone\\/naltrexone and SR 141716 alone and in combination were examined on beer consumption in rats. Methods In a progressive ratio paradigm rats were trained to lick at a tube for either

  18. Genome-Wide Mapping of Chromatin State of Mouse Forelimbs

    PubMed Central

    Eng, Diana; Vogel, Walter K; Flann, Nicholas S; Gross, Michael K; Kioussi, Chrissa

    2014-01-01

    Background Cell types are defined at the molecular level during embryogenesis by a process called pattern formation and created by the selective utilization of combinations of sequence specific transcription factors. Developmental programs define the sets of genes that are available to each particular cell type, and real-time biochemical signaling interactions define the extent to which these sets are used at any given time and place. Gene expression is regulated through the integrated action of many cis-regulatory elements, including core promoters, enhancers, silencers, and insulators. The chromatin state in developing body parts provides a code to cellular populations that direct their cell fates. Chromatin profiling has been a method of choice for mapping regulatory sequences in cells that go through developmental transitions. Results We used antibodies against histone H3 lysine 4 trimethylations (H3K4me3) a modification associated with promoters and open/active chromatin, histone H3 lysine 27 trimethylations (H3K27me3) associated with Polycomb-repressed regions and RNA polymerase II (Pol2) associated with transcriptional initiation to identify the chromatin state signature of the mouse forelimb during mid-gestation, at embryonic day 12 (E12). The families of genes marked included those related to transcriptional regulation and embryogenesis. One third of the marked genes were transcriptionally active while only a small fraction were bivalent marked. Sequence specific transcription factors that were activated were involved in cell specification including bone and muscle formation. Conclusion Our results demonstrate that embryonic limb cells do not exhibit the plasticity of the ES cells but are rather programmed for a finer tuning for cell lineage specification. PMID:25530700

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

    PubMed

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

    2010-04-01

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

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

    PubMed

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

    2014-03-15

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

  1. Exercise Training Reduces Cardiac Dysfunction and Remodeling in Ovariectomized Rats Submitted to Myocardial Infarction

    PubMed Central

    de Almeida, Simone Alves; Claudio, Erick Roberto Gonçalves; Mengal, Vinícius Franskoviaky; de Oliveira, Suelen Guedes; Merlo, Eduardo; Podratz, Priscila Lang; Gouvêa, Sônia Alves; Graceli, Jones Bernardes; de Abreu, Gláucia Rodrigues

    2014-01-01

    The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI. PMID:25551214

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

    PubMed

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

    2013-05-27

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

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

    PubMed

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

    2009-10-01

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

  4. Effectiveness of topical anesthetics on reducing tactile sensitivity in the paws of newborn rats.

    PubMed

    Strain, Misty M; Vineyard, Mary Ann; Roberto, Megan E; Brumley, Michele R

    2014-01-01

    The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.5% prilocaine), alcaine (.5% proparacaine), triocaine (20% benzocaine, 6% lidocaine, and 4% tetracaine), or petroleum jelly (treatment control). Touch thresholds significantly increased after treatment with EMLA 18% of the time, and there was no evidence of a systemic effect. Touch thresholds were not significantly altered after treatment with alcaine, triocaine, or petroleum jelly. Therefore, EMLA appears to be a slightly effective topical anesthetic for reducing tactile sensitivity in newborn rats. PMID:23254968

  5. Morphology and function of the forelimb in arboreal frogs: specializations for grasping ability?

    PubMed Central

    Manzano, Adriana S; Abdala, Virginia; Herrel, Anthony

    2008-01-01

    Frogs are characterized by a unique morphology associated with their saltatory lifestyle. Although variation in the form and function of the pelvic girdle and associated appendicular system related to specialized locomotor modes such as swimming or burrowing has been documented, the forelimbs have typically been viewed as relatively unspecialized. Yet, previous authors have noted versatility in forelimb function among arboreal frogs associated with feeding. Here we study the morphology and function of the forelimb and hand during locomotion in two species of arboreal frogs (Litoria caerulea and Phyllomedusa bicolor). Our data show a complex arrangement of the distal forelimb and hand musculature with some notable differences between species. Analyses of high-speed video and video fluoroscopy recordings show that forelimbs are used in alternating fashion in a diagonal sequence footfall pattern and that the position of the hand is adjusted when walking on substrates of different diameters. Electromyographic recordings show that the flexors of the hand are active during substrate contact, suggesting the use of gripping to generate a stabilizing torque. Measurements of grasping forces in vivo and during stimulation experiments show that both species, are capable of executing a so-called power grip but also indicates marked differences between species, in the magnitude of forces generated. Stimulation experiments showed an increased control of digit flexion in the more specialized of the two species, allowing it to execute a precision grip paralleled only by that seen in primates. PMID:18565111

  6. Forelimb preferences in human beings and other species: multiple models for testing hypotheses on lateralization

    PubMed Central

    Versace, Elisabetta; Vallortigara, Giorgio

    2015-01-01

    Functional preferences in the use of right/left forelimbs are not exclusively present in humans but have been widely documented in a variety of vertebrate and invertebrate species. A matter of debate is whether non-human species exhibit a degree and consistency of functional forelimb asymmetries comparable to human handedness. The comparison is made difficult by the variability in hand use in humans and the few comparable studies conducted on other species. In spite of this, interesting continuities appear in functions such as feeding, object manipulation and communicative gestures. Studies on invertebrates show how widespread forelimb preferences are among animals, and the importance of experience for the development of forelimb asymmetries. Vertebrate species have been extensively investigated to clarify the origins of forelimb functional asymmetries: comparative evidence shows that selective pressures for different functions have likely driven the evolution of human handedness. Evidence of a complex genetic architecture of human handedness is in line with the idea of multiple evolutionary origins of this trait. PMID:25798121

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

    PubMed

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

    2014-03-15

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

  8. Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

    PubMed

    Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

    2014-09-01

    Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo ?CT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced ?CT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity exercised a positive effect in healthy control joints, which increased cartilage sGAG content. More research on this topic might lead to novel insights as to improve cartilage quality. PMID:24933343

  9. Inhaled Lactonase Reduces Pseudomonas aeruginosa Quorum Sensing and Mortality in Rat Pneumonia

    PubMed Central

    Lafleur, John; Lepidi, Hubert; Papazian, Laurent; Rolain, Jean-Marc; Raoult, Didier; Elias, Mikael; Silby, Mark W.; Bzdrenga, Janek; Bregeon, Fabienne; Chabriere, Eric

    2014-01-01

    Rationale The effectiveness of antibiotic molecules in treating Pseudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. The existence of bacterial communication systems, such as quorum sensing, has provided new opportunities of treatment. Lactonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-Pseudomonas drugs that might be evaluated in pneumonia. Objectives The aim of the present study was to evaluate the ability of a lactonase called SsoPox-I to reduce the mortality of a rat P. aeruginosa pneumonia. Methods To assess SsoPox-I-mediated quorum quenching, we first measured the activity of the virulence gene lasB, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a PAO1 strain grown in the presence of lactonase. In an acute lethal model of P. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with SsoPox-I on the mortality, lung bacterial count and lung damage. Measurements and Primary Results SsoPox-I decreased PAO1 lasB virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. The early use of SsoPox-I reduced the mortality of rats with acute pneumonia from 75% to 20%. Histological lung damage was significantly reduced but the lung bacterial count was not modified by the treatment. A delayed treatment was associated with a non-significant reduction of mortality. Conclusion These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use. PMID:25350373

  10. Cutaneous magnetic stimulation reduces rat chronic pain via activation of the supra-spinal descending pathway.

    PubMed

    Shiiba, Shun-ji; Yamamoto, Satoru; Sasaki, Hironori; Nishi, Mitsuharu; Ishikawa, Kozo; Yasuda, Seiko; Tokuda, Nobuko; Nakanishi, Osamu; Ishikawa, Toshizo

    2012-03-01

    Recent studies have demonstrated that magnetic stimulation (MS) can induce cellular responses such as Ca(2+) influx into the cultured neurons and glia, leading to increased intracellular phosphorylation. We have demonstrated previously that MS reduces rat neuropathic pain associated with the prevention of neuronal degeneration. Thus, we aimed to elucidate the actions of MS in relation to modulation of spinal neuron-glia and the descending inhibitory system in chronic pain. The male SD rats intrathecally implanted with catheters were subjected to sciatic nerve ligation (CCI). MS is a low power apparatus characterized by two different frequencies, 2 KHz and 83 MHz. Rats were given MS to the skin (injured sciatic nerve) for 10 min from the seventh day after CCI. The paw withdrawal latency (PWL) evoked by thermal stimuli was measured for 14 days after CCI. Immunohistochemistry for Iba-1 or GFAP was performed after 4% paraformaldehyde fixation (microscopic analysis). We employed microdialysis for measuring CSF 5-HIAA as a reflection of 5-HT release by MS stimulation. Following CCI, rats showed a decrease in PWL after CCI, and the decrease continued until the 14th day. With MS treatment, the decrease in PWL was reduced during the 10-14 day after CCI. Injection of JNK-1 inhibitors on the 14th day antagonized the analgesic effect of MS. MS also eliminated the CCI-induced decrease in GFAP immunoreactivity. Moreover, MS evoked spinal 5-HT release reflected by increase in spinal 5-HIAA level. Thus, we demonstrate that a novel magnetic stimulator used cutaneously can ameliorate chronic pain by not only preventing abnormal spinal neuron-glia interaction, but also through the activation of the supra-spinal descending inhibitory system. PMID:21968643

  11. Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.

    PubMed

    Bell, Richard L; Eiler, Bill J A; Cook, Jason B; Rahman, Shafiqur

    2009-12-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of many drugs of abuse, including ethanol. The present study examined the efficacy of cytisine, a nAChR partial agonist, and lobeline, a putative nAChR antagonist, on the maintenance of ethanol drinking by HAD-2 rats. Adult male HAD-2 rats were given access to ethanol (15 and 30%, with ad libitum access to water and food) 22 h/day for 12 weeks, beginning at 60 days of age, after which cytisine (0.0, 0.5, and 1.5 mg/kg) was tested for 3 consecutive days. The rats were given an 18-day washout period and were then tested with lobeline (0.0, 1.0, and 5.0 mg/kg) for 3 consecutive days. Ethanol intake was measured at 1, 4, and 22 h postinjection. Rats were injected intraperitoneally just before lights out (1200 h). There was a significant main effect of cytisine treatment on the second test day, with the 1.5 mg/kg dose significantly reducing ethanol intake at the 1- and 4-h time-points, relative to saline, and the 0.5 mg/kg dose inducing a significant reduction at the 4-h time-point. Conversely, lobeline treatment resulted in significant main effects of treatment for all three time-points within each test day, with the 5.0 mg/kg dose significantly reducing ethanol intake, relative to saline, at each time-point within each test day. These findings provide further evidence that activity at the nAChR influences ethanol intake and is a promising target for pharmacotherapy development for the treatment of alcohol dependence and relapse. PMID:20004336

  12. Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats

    PubMed Central

    Bell, Richard L.; Eiler, Bill J. A.; Cook, Jason B.; Rahman, Shafiqur

    2010-01-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of many drugs of abuse, including ethanol. The present study examined the efficacy of cytisine, a nAChR partial agonist, and lobeline, a putative nAChR antagonist, on the maintenance of ethanol drinking by HAD-2 rats. Adult male HAD-2 rats were given access to ethanol (15% and 30%, with ad lib water and food) 22 hr per day for 12 weeks, beginning at 60 days old, after which cytisine (0.0, 0.5 and 1.5 mg/kg) was tested for 3 consecutive days. The rats were given an 18 day wash-out period, and were then tested with lobeline (0.0, 1.0 and 5.0 mg/kg) for 3 consecutive days. Ethanol intake was measured at 1, 4 and 22 hours post-injection. Rats were injected i.p. just prior to lights out (1200 h). There was a significant main effect of cytisine treatment on the 2nd test day, with the 1.5 mg/kg dose significantly reducing ethanol intake at the 1 hr and 4 hr time-points, relative to saline, and the 0.5 mg/kg dose inducing a significant reduction at the 4 hr time-point. Conversely, lobeline treatment resulted in significant main effects of treatment for all 3 time points, within each test day, with the 5.0 mg/kg dose significantly reducing ethanol intake, relative to saline, at each time-point within each test day. These findings provide further evidence that activity at the nAChR influences ethanol intake and is a promising target for pharmacotherapy development for the treatment of alcohol dependence and relapse. PMID:20004336

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

    PubMed

    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

    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

  14. Both compensation and recovery of skilled reaching following small photothrombotic stroke to motor cortex in the rat

    Microsoft Academic Search

    Seong-Keun Moon; Mariam Alaverdashvili; Albert R. Cross; Ian Q. Whishaw

    2009-01-01

    Large lesions produced by stroke to the forelimb region of motor cortex of the rat feature post-stroke improvement that in the main is due to compensation. The present study describes both recovery and compensation of forelimb use in a reach-to-eat (skilled reaching) task following small photothrombotic stroke. The rats were pretrained before stroke, and then assessed using endpoint measures and

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

    PubMed

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

    2012-02-01

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

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

    SciTech Connect

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

    1988-08-01

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

  17. Vagus nerve stimulation reduces body weight and fat mass in rats.

    PubMed

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Marrosu, Francesco; Puligheddu, Monica; Floris, Gabriele; Asuni, Gino Paolo; Cappai, Angela Letizia; Deriu, Silvia; Follesa, Paolo

    2012-01-01

    Among the manifold effects of vagus nerve stimulation (VNS) delivered as an add-on treatment to patients with drug-resistant epilepsy, a moderate loss of body weight has been observed in some individuals. We have now investigated this effect in rats. Exposure of rats to VNS for 4 weeks reduced feed conversion efficiency as well as body weight gain (by ?25%) and the amount of mesenteric adipose tissue (by ?45%) in comparison with those in sham-operated control animals. A pair-fed experiment showed that both lower dietary intake and increase energy expenditure independently contributed to the reduction of body weight and mesenteric adipose tissue. Moreover, VNS increased the level of non-esterified fatty acids in plasma and mesenteric adipose tissue by ?50 and 80%, respectively, without affecting that in the liver. In addition, VNS reduced the amounts of endocannabinoids and increased N-palmitoylethanolamide, an endogenous ligand of the transcription factor PPAR? (peroxisome proliferator-activated receptor ?) in mesenteric adipose tissue but not in the hypothalamus. These effects were accompanied by increased expression of the gene for brain-derived neurotrophic factor (BDNF) in the hypothalamus and up-regulation of the abundance of PPAR? in the liver. Our results suggest that the reduction in body fat induced by VNS in rats may result from the action of both central and peripheral mediators. The reduced feed conversion efficiency associated with VNS may be mediated by hypothalamic BDNF, down-regulation of endocannabinoid tone in mesenteric adipose tissue and a PPAR?-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure. PMID:23028630

  18. Vagus Nerve Stimulation Reduces Body Weight and Fat Mass in Rats

    PubMed Central

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Marrosu, Francesco; Puligheddu, Monica; Floris, Gabriele; Asuni, Gino Paolo; Cappai, Angela Letizia; Deriu, Silvia; Follesa, Paolo

    2012-01-01

    Among the manifold effects of vagus nerve stimulation (VNS) delivered as an add-on treatment to patients with drug-resistant epilepsy, a moderate loss of body weight has been observed in some individuals. We have now investigated this effect in rats. Exposure of rats to VNS for 4 weeks reduced feed conversion efficiency as well as body weight gain (by ?25%) and the amount of mesenteric adipose tissue (by ?45%) in comparison with those in sham-operated control animals. A pair-fed experiment showed that both lower dietary intake and increase energy expenditure independently contributed to the reduction of body weight and mesenteric adipose tissue. Moreover, VNS increased the level of non-esterified fatty acids in plasma and mesenteric adipose tissue by ?50 and 80%, respectively, without affecting that in the liver. In addition, VNS reduced the amounts of endocannabinoids and increased N-palmitoylethanolamide, an endogenous ligand of the transcription factor PPAR? (peroxisome proliferator–activated receptor ?) in mesenteric adipose tissue but not in the hypothalamus. These effects were accompanied by increased expression of the gene for brain-derived neurotrophic factor (BDNF) in the hypothalamus and up-regulation of the abundance of PPAR? in the liver. Our results suggest that the reduction in body fat induced by VNS in rats may result from the action of both central and peripheral mediators. The reduced feed conversion efficiency associated with VNS may be mediated by hypothalamic BDNF, down-regulation of endocannabinoid tone in mesenteric adipose tissue and a PPAR?-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure. PMID:23028630

  19. Glucan and glutamine reduce bacterial translocation in rats subjected to intestinal ischemia-reperfusion.

    PubMed

    Medeiros, Aldo Cunha; Chacon, Dâmaso Araújo; Sales, Valéria Soraya Farias; Egito, Eryvaldo Sócrates Tabosa; Brandão-Neto, José; Pinheiro, Laíza Araújo Mohana; Carvalho, Mariana Rego

    2006-01-01

    Intestinal ischemia/reperfusion (I/R) may induce bacterial translocation (BT). Glutamine (GLN)-enriched nutrition decreases BT. However, little is known about the effect of glucan (GL) in BT. This study investigated the combined effect of GL/GLN on BT, intestinal damage, and portal blood cytokines in animals under I/R. Four groups of 10 rats each were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. The control group (group 1) received only rat food/water, group 2 received glutamine via gavage, group 3 received subcutaneuos soluble (1, 3)-d-glucan, and group 4 received GL + GLN. A sham group (group 5) served as a normal control. Bacterial cultures of ileum, mesenteric lymph nodes (MLN), liver and lung biopsies, histological changes of ileum, and serum cytokines variables were examined after I/R. Data were analyzed by analysis of variance (ANOVA) and the Newman-Keuls test. Results showed that GLN, GL, and GL/GLN significantly reduced BT to MLN, liver, and lung. BT was more attenuated after GL treatment than GLN (P < .05). Rats treated with both GL and GLN exhibited lower bacterial colony counts than the ones treated only with GLN or GL. Severe mucosal damage on histological findings was shown in group 1, but these findings were significantly ameliorated (P < .05) in groups 3 and 4. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels in portal serum were significantly reduced and IL-10 was increased by GL and GLN treatment. In conclusion, the use of GL was more effective than GLN in reducing BT, intestinal damage, and cytokine levels after I/R. Additionally, the combination of GL and GLN improved results. PMID:16546928

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

    PubMed

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

    2015-02-01

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

  1. Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats.

    PubMed

    Park, Seung-Kyu; Qi, Xu-Feng; Song, Soon-Bong; Kim, Dong-Heui; Teng, Yung-Chien; Yoon, Yang-Suk; Kim, Kwang-Yong; Li, Jian-Hong; Jin, Dan; Lee, Kyu-Jae

    2009-10-01

    Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms. PMID:19887722

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

    PubMed Central

    Bhattacharya, Koushik; Mukherjee, Soumya

    2014-01-01

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

  3. Three-dimensional kinematics of the equine distal forelimb: effects of a sharp turn at the walk

    Microsoft Academic Search

    H. CHATEAU; C. DEGUEURCE; J.-M. DENOIX

    2010-01-01

    Summary Reasons for performing study: Sharp turns are suspected to increase expression of several distal forelimb lamenesses even at the walk but the biomechanical consequences of such a movement remain unknown. Objective: To quantify the effects of a sharp turn at the walk on the 3-dimensional movements of the distal segments of the forelimb. Methods: Kinematics of the distal segments

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

    PubMed Central

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

    2014-01-01

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

  5. Fermented soy permeate reduces cytokine level and oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Malardé, Ludivine; Groussard, Carole; Lefeuvre-Orfila, Luz; Vincent, Sophie; Efstathiou, Théo; Gratas-Delamarche, Arlette

    2015-01-01

    Oxidative stress and inflammation are involved in the development of type 1 diabetes and its complications. Because two compounds found in soy, that is, isoflavones and alpha-galactooligosaccharides, have been shown to exert antioxidant and anti-inflammatory effects, this study aimed to assess the effects of a dietary supplement containing these two active compounds, the fermented soy permeate (FSP). We hypothesized that FSP would be able to reduce in vivo oxidative stress and inflammation in streptozotocin (STZ)-induced type 1 diabetic rats. Thirty male Wistar rats were divided into the control placebo, diabetic placebo, and diabetic FSP-supplemented groups. They received daily, by oral gavage, water (placebo groups) or diluted FSP (0.1?g/day; FSP-supplemented group). After 3 weeks, glycemic regulation (glycemia and fructosamine level); the plasma level of carboxymethyllysine (CML), a marker of systemic oxidative stress in diabetes; and the plasma levels of inflammatory markers (CRP, IL-1?, IL-6, and uric acid) were evaluated. Markers of oxidative damage (isoprostanes and GSH/GSSG), antioxidant enzymatic activity (SOD and GPX), and Mn-SOD content were determined in skeletal muscle (gastrocnemius). Diabetic placebo rats exhibited higher CML levels, lower SOD and GPX activities, and decreased Mn-SOD contents. FSP supplementation in diabetic animals normalized the CML and antioxidant enzymatic activity levels and tended to increase Mn-SOD expression. The markers of inflammation whose levels were increased in the diabetic placebo group were markedly decreased by FSP (IL-1?: -75%, IL-6: -46%, and uric acid: -17%), except for CRP. Our results demonstrate that FSP exhibited antioxidant and anti-inflammatory properties in vivo in STZ-induced diabetic rats. PMID:25314273

  6. Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring.

    PubMed

    Wu, Zhixiong; Siuda, Daniel; Xia, Ning; Reifenberg, Gisela; Daiber, Andreas; Münzel, Thomas; Förstermann, Ulrich; Li, Huige

    2015-01-01

    Pentaerythritol tetranitrate is devoid of nitrate tolerance and shows no reproductive or developmental toxicity in animal studies. Recently, pentaerythritol tetranitrate has been demonstrated to reduce the risk of intrauterine growth restriction and the risk of preterm birth in women with abnormal placental perfusion. This study was conducted to test the perinatal programming effect of pentaerythritol tetranitrate in spontaneously hypertensive rats, a rat model of genetic hypertension. Parental spontaneously hypertensive rats were treated with pentaerythritol tetranitrate (50 mg/kg per day) during pregnancy and lactation periods; the offspring received standard chow without pentaerythritol tetranitrate after weaning. Maternal treatment with pentaerythritol tetranitrate had no effect on blood pressure in male offspring. In the female offspring, however, a persistent reduction in blood pressure was observed at 6 and 8 months. This long-lasting effect was accompanied by an upregulation of endothelial nitric oxide synthase, mitochondrial superoxide dismutase, glutathione peroxidase 1, and heme oxygenase 1 in the aorta of 8-month-old female offspring, which was likely to result from epigenetic changes (enhanced histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation) and transcriptional activation (enhanced binding of DNA-directed RNA polymerase II to the transcription start site of the genes). In organ chamber experiments, the endothelium-dependent, nitric oxide-mediated vasodilation to acetylcholine was enhanced in aorta from female offspring of the pentaerythritol tetranitrate-treated parental spontaneously hypertensive rats. In conclusion, maternal pentaerythritol tetranitrate treatment leads to epigenetic modifications, gene expression changes, an improvement of endothelial function and a persistent blood pressure reduction in the female offspring. PMID:25385760

  7. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

    PubMed

    Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J

    2003-12-01

    Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model. PMID:14680076

  8. Soyo-san reduces depressive-like behavior and proinflammatory cytokines in ovariectomized female rats

    PubMed Central

    2014-01-01

    Background Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The role of pro- and anti-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. In the present study, we detected the antidepressant effect of soyo-san in the ovariectomized and repeated stressed female rats. Methods This study was designed to evaluate the antidepressant-like effect of soyo-san on the forced swimming test (FST). The rats were randomly divided into the following groups: the nonoperated and nonstressed group (non-op), the nonoperated and stressed group (non-op?+?ST), the ovariectomized and stress group (OVX) and sham operated and stressed group (sham), the ovariectomized and stressed group (OVX?+?ST), the ovariectomized, stressed and soyo-san 100 mg/kg treated group (SOY100) and the ovariectomized, stressed and soyo-san 400 mg/kg treated group (SOY400). The rats were exposed to immobilization stress (IMO) for 14day (2 h/14day), and soyo-san (100 mg/kg and 400 mg/kg) was administrated during the same time. In the same animals, the levels of corticosterone and interleukin-1-beta (IL-1?) were examined in the serum. Also, the change of IL-1? expression in brain regions was examined after behavior test. Results In the FST, the lower dose (100 mg/kg) of extract was effective in reducing immobility, along with an increase in swimming time. The serum levels of corticosterone and IL-1? in the SOY groups were significantly lower than those in the control group. In the brain, the expression of IL-1? positive neurons in the control group were significantly increased in the paraventricular nucleus (PVN) and hippocampus compared to the non-op. However, soyo-san groups significantly reduced the IL-1?-ir neurons in the PVN and hippocampal regions compared to the control. Conclusion The present results demonstrated that soyo-san effectively reduced behavioral and patho-physiological depression-like responses. Trial registration: Our results suggest that soyo-san may be useful for immune regulator in repeated stress-induced ovariectomized female rats. PMID:24444307

  9. Aqueous Extract of Ipomoea batatas Reduces Food Intake in Male Wistar Rats: A Pilot Study

    PubMed Central

    Olubobokun, TH; Aluko, EO; Iyare, EE; Anyaehie, USB; Olatunbosun, ED; Aizenabor, GI

    2014-01-01

    Background: Food intake is regulated by the complex interaction of psychological and physiological events associated with ingestion. Food that increases short-term satiety decreases the amount of energy ingested subsequently and thus could potentially help in weight management in the long run. Potato, a common starchy tuber in our environment is believed to contain substances that can help maintain and increases short-term satiety. Aim: This study was conducted to determine the effect of the aqueous extract of sweet potato (Ipomoea batatas [IB]) on food intake in male Wistar rats. Materials and Methods: The sweet potato tubers were chopped into small pieces and homogenized in distilled water for 30 s. Homogenate was filtered through muslin cloth and then centrifuged at 120 rpm for 20 min. For use, the residue was evaporated to dryness. The dried extract was reconstituted in freshly prepared normal saline for administration to test animals. The 20 acclimatized male Wistar rats weighing 170-180 g were used for this study. The animals were randomly assigned into four groups of five rats each. Group 1 served as the control and was fed with 0.3 ml of normal saline while Groups 2-4 were fed with IB extract. Results: The results showed that in the extract-treated groups, the food intake was significantly reduced at P < 0.01 in a dose dependent manner when compared with the control group. Conclusion: Consumption of IB caused a reduction in food intake probably by reducing appetite and increasing satiety. PMID:25221722

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

    PubMed Central

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

    2012-01-01

    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; DA0, DA5, DA10 and DA20, 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/cm2), but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg). While DA20 abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight) and inflammatory cell abundance (6.0 ± 0.79 cells/cm2), 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

  11. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    PubMed

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

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

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

    SciTech Connect

    Wilkes, B.M.

    1987-04-01

    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.

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

    PubMed Central

    DING, MEI; SI, DAOYUAN; ZHANG, WENQI; FENG, ZHAOHUI; HE, MIN; YANG, PING

    2014-01-01

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

  14. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats.

    PubMed

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero

    2014-12-01

    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times. PMID:25281203

  15. Reduced mechanical efficiency in left?ventricular trabeculae of the spontaneously hypertensive rat

    PubMed Central

    Han, June?Chiew; Tran, Kenneth; Johnston, Callum M.; Nielsen, Poul M. F.; Barrett, Carolyn J.; Taberner, Andrew J.; Loiselle, Denis S.

    2014-01-01

    Abstract Long?term systemic arterial hypertension, and its associated compensatory response of left?ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left?ventricular trabeculae from SHR?F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR?NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR?F differed little from that of the SHR?NF, both SHR groups performed less stress?length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca2+ cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension?induced left?ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced. PMID:25413328

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2009-01-01

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

  19. Eribis Peptide 94 Reduces Infarct Size in Rat Hearts Via Activation of Centrally Located ? Opioid Receptors

    PubMed Central

    Gross, Garrett J.; Hsu, Anna; Nithipatikom, Kasem; Bobrova, Irina; Bissessar, Erik

    2011-01-01

    Eribis peptide 94 (EP 94) is a novel enkephalin derivative which binds with high potency to ? and ? opioid receptors with less affinity for the ? opioid receptor. This compound has recently been shown to produce an acute reduction in myocardial infarct size in the anesthetized pig and rat partially via an eNOS- and KATP channel-dependent mechanism. EP 94 also was found to produce a chronic reduction in infarct size 24 hrs post drug administration via the upregulation of iNOS in rats. In spite of these findings, no data have emerged in which the opioid receptor subtype responsible for cardioprotection has been identified and the site of action, heart, other peripheral organs or the CNS have not been addressed. In the current study, EP 94, was administered in 2 divided doses (0.5 ug/kg, iv) at 5 and 10 min into the ischemic period and the opioid antagonists were administered 10 min prior to the onset of the 30 min ischemic period. The selective antagonists used were the ? receptor antagonist CTOP, the ? receptor antagonists, naltrindole and BNTX and the ? receptor antagonist, nor-BNI. Surprisingly, only CTOP completely blocked the cardioprotective effect of EP 94, whereas, naltrindole, BNTX and nor-BNI had modest but nonsignificant effects. Since there is controversial evidence suggesting that ? receptors may be absent in the adult rat myocardium, it was hypothesized that the protective effect of EP 94 may be mediated by an action outside the heart, perhaps in the CNS. To test this hypothesis, rats were pretreated with the nonselective opioid antagonist, naloxone HCl (NAL), which penetrates the blood brain barrier (BBB) or naloxone methiodide (NME), the quaternary salt of NAL, which does not penetrate the BBB prior to EP 94 administration. In support of a CNS site of action for EP 94, NAL completely blocked its cardioprotective effect, whereas, NME had no effect. These results suggest that EP 94 reduces IS/AAR in the rat primarily via activation of central ? opioid receptors. PMID:22130105

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

    PubMed Central

    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, Åke; Hessner, Martin J.

    2014-01-01

    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. PMID:23111281

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

    PubMed

    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

    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

  2. Instillation of Taurolidine\\/Heparin after Laparotomy Reduces Intraperitoneal Tumour Growth in a Colon Cancer Rat Model

    Microsoft Academic Search

    I. Opitz; H. Van der Veen; N. Witte; C. Braumann; J. M. Mueller; C. A. Jacobi

    2007-01-01

    Objective: To investigate whether irrigation of the abdominal cavity after laparotomy for caecum resection with taurolidine\\/heparin or adhesion prophylactic substances reduces intraperitoneal tumour growth or the local recurrence rate in a colon carcinoma rat model. Methods: 60 BDIX rats underwent caecum resection after intraperitoneal inoculation of 1 × 104 colon carcinoma cells (DHD\\/K12\\/TRb). Intergel®, Interceed®, taurolidine\\/heparin or NaCl 0.9% were

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

    Microsoft Academic Search

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

    2000-01-01

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

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

    Microsoft Academic Search

    I. V. Zarubina; P. D. Shabanov

    2009-01-01

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

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

    E-print Network

    D'Août, Kristiaan

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

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

    PubMed

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

    2013-02-01

    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

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

    PubMed Central

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

    1997-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.

    PubMed

    Liu, Da; Huang, Ying; Li, Bin; Jia, Changqing; Liang, Feng; Fu, Qin

    2015-02-01

    Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-?B ligand (receptor activator of nuclear factor-?B ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-?, interleukin (IL)-1? and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats. PMID:25424914

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

    PubMed Central

    2014-01-01

    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. PMID:24417801

  11. N-acetyl cysteine (NAC) treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus

    PubMed Central

    Falluel-Morel, Anthony; Lin, Lulu; Sokolowski, Katie; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2011-01-01

    Mercury is an environmental toxicant that can disrupt brain development. However, while progress has been made in defining its neurotoxic effects, we know far less about available therapies that can effectively protect brain in exposed individuals. We previously developed an animal model in which we defined the sequence of events underlying neurotoxicity: Methylmercury (MeHg) injection in postnatal rat acutely induced inhibition of mitosis and stimulated apoptosis in the hippocampus, that later resulted in intermediate term deficits in structure size and cell number. NAC is the N-acetyl derivative of L-cysteine used clinically for treatment of drug intoxication. Here, based on its known efficacy in promoting MeHg urinary excretion, we evaluated NAC for protective effects in the developing brain. In immature neurons and precursors MeHg (3µM) induced a >50% decrease in DNA synthesis at 24hr, an effect that was completely blocked by NAC co-incubation. In vivo, injection of MeHg (5µg/gbw) into 7 day-old rats induced a 22% decrease in DNA synthesis in whole hippocampus and a 4-fold increase in activated caspase-3 immunoreactive cells at 24hr, and reduced total cell numbers by 13% at 3 weeks. Treatment of MeHg exposed rats with repeated injections of NAC abolished MeHg toxicity. NAC prevented the reduction in DNA synthesis and the marked increase in caspase-3 immunoreactivity. Moreover, the intermediate term decrease in hippocampal cell number provoked by MeHg was fully blocked by NAC. Altogether, these results suggest that MeHg toxicity in the perinatal brain can be ameliorated by using NAC, opening potential avenues for therapeutic intervention. PMID:22420031

  12. Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

    PubMed

    Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

    2014-11-01

    The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p < 0.001) reduction of 24-h ethanol consumption. When ethanol intake was determined within the first 2 h of darkness, the reduction was 85-90% (p < 0.001). We determined whether animals chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 ?M vs. 7 ?M; p < 0.001). Liver catalase activity following fenofibrate treatment was increased 3-fold (p < 0.01). Other hepatic enzymes responsible for the metabolism of ethanol (alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1 g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. PMID:25241056

  13. Intracellular acidification reduced gap junction coupling between immature rat neocortical pyramidal neurones.

    PubMed Central

    Rörig, B; Klausa, G; Sutor, B

    1996-01-01

    1. Developmental changes in electrophysiological properties of pyramidal neurones correlated with the developmental decline in gap junction-dependent dye coupling were investigated in coronal slices of rat prefrontal and sensorimotor cortex. Effects of intracellular acidification induced by application of weak organic acids on neuronal dye coupling, electrotonic parameters as well as synaptic potentials were examined using the patch clamp technique. Optical monitoring of intracellular pH revealed an acidic shift of 0.4-0.5 pH units following sodium propionate application. 2. Dye coupling between layer II-III neurones was prominent during the first two postnatal weeks. During this period, pre-incubation of slices with 30 mM of the sodium salts of weak organic acids reduced the number of cells coupled to the injected neurones by 64%. 3. Between postnatal days 1 and 18, the mean neuronal input resistance decreased significantly (by 81.0%). Both the membrane time constant (tau 0) and the first equalizing time constant (tau 1) also showed a significant developmental decline of 25.8 and 65.8%, respectively. Electrotonic length decreased by 34.9%. The electrophysiological properties of neurones displayed a pronounced intercellular variability which decreased with on-going development. 4. During the first two postnatal weeks, intracellular acidification led to a mean increase in neuronal input resistance of 55.9% and a mean decreae in electrotonic length of 22.2%. The membrane time constant was reduced by approximately 25% in the majority of neurones tested. Significant electrophysiological effects induced by intracellular acidification were not detected in uncoupled neurones from 18-day-old rats. 5. EPSP width at half-maximal amplitude showed a substantial reduction of approximately 50%, while rise times of the non-NMDA receptor-mediated EPSP components displayed no significant change during development. Both weak organic acids, as well as the gap junction blocker 1-octanol, reduced excitatory synaptic transmission independent of developmental age. 6. We conclude that gap junction permeability is regulated by intracellular pH in developing layer II-III pyramidal cells in the rat neocortex. The prominent correlation between pH-induced reduction in dye coupling and changes in electrophysiological cell properties suggests a significant influence of gap junctions on synaptic integration and information transfer in the immature neocortex. Images Figure 4 PMID:8745277

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

    PubMed Central

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

    2009-01-01

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

  15. Postnatal Maturation of the Red Nucleus Motor Map Depends on Rubrospinal Connections with Forelimb Motor Pools

    PubMed Central

    Williams, Preston T. J. A.; Kim, Sangsoo

    2014-01-01

    The red nucleus (RN) and rubrospinal tract (RST) are important for forelimb motor control. Although the RST is present postnatally in cats, nothing is known about when rubrospinal projections could support motor functions or the relation between the development of the motor functions of the rubrospinal system and the corticospinal system, the other major system for limb control. Our hypothesis is that the RN motor map is present earlier in development than the motor cortex (M1) map, to support early forelimb control. We investigated RN motor map maturation with microstimulation and RST cervical enlargement projections using anterograde tracers between postnatal week 3 (PW3) and PW16. Microstimulation and tracer injection sites were verified histologically to be located within the RN. Microstimulation at PW4 evoked contralateral wrist, elbow, and shoulder movements. The number of sites producing limb movement increased and response thresholds decreased progressively through PW16. From the outset, all forelimb joints were represented. At PW3, RST projections were present within the cervical intermediate zone, with a mature density of putative synapses. In contrast, beginning at PW5 there was delayed and age-dependent development of forelimb motor pool projections and putative rubromotoneuronal synapses. The RN has a more complete forelimb map early in development than previous studies showed for M1, supporting our hypothesis of preferential rubrospinal rather than corticospinal control for early movements. Remarkably, development of the motor pool, not intermediate zone, RST projections paralleled RN motor map development. The RST may be critical for establishing the rudiments of motor skills that subsequently become refined with further CST development. PMID:24647962

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

    PubMed Central

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

    2014-01-01

    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. PMID:25009604

  17. A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

    PubMed Central

    Elburki, Muna S.; Rossa, Carlos; Guimaraes, Morgana R.; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A.; Zhang, Yu; Johnson, Francis; Golub, Lorne M.

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by ?-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1?; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or ?-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

  18. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.

    PubMed

    Elburki, Muna S; Rossa, Carlos; Guimaraes, Morgana R; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A; Zhang, Yu; Johnson, Francis; Golub, Lorne M

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by ?-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1?; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or ?-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

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

    PubMed

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

    2012-01-01

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

  20. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    SciTech Connect

    Noble, E.P.; Ritchie, T. (Univ. of California, Los Angeles (USA))

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with (3H)inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of (3H)inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.

  1. Prepubertal exposure to cow’s milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    PubMed Central

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

    2010-01-01

    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. PMID:20232392

  2. Reduced brown adipose tissue thermogenesis during environmental interactions in transgenic rats with ataxin-3-mediated ablation of hypothalamic orexin neurons.

    PubMed

    Mohammed, Mazher; Ootsuka, Youichirou; Yanagisawa, Masashi; Blessing, William

    2014-10-15

    Thermogenesis in brown adipose tissue (BAT) contributes to substantial increases in body temperature evoked by threatening or emotional stimuli. BAT thermogenesis also contributes to increases in body temperature that occur during active phases of the basic rest-activity cycle (BRAC), as part of normal daily life. Hypothalamic orexin-synthesizing neurons influence many physiological and behavioral variables, including BAT and body temperature. In conscious unrestrained animals maintained for 3 days in a quiet environment (24-26°C) with ad libitum food and water, we compared temperatures in transgenic rats with ablation of orexin neurons induced by expression of ataxin-3 (Orx_Ab) with wild-type (WT) rats. Both baseline BAT temperature and baseline body temperature, measured at the onset of BRAC episodes, were similar in Orx_Ab and WT rats. The time interval between BRAC episodes was also similar in the two groups. However, the initial slopes and amplitudes of BRAC-related increases in BAT and body temperature were reduced in Orx_Ab rats. Similarly, the initial slopes and amplitudes of the increases in BAT temperatures induced by sudden exposure to an intruder rat (freely moving or confined to a small cage) or by sudden exposure to live cockroaches were reduced in resident Orx_Ab rats. Constriction of the tail artery induced by salient alerting stimuli was also reduced in Orx_Ab rats. Our results suggest that orexin-synthesizing neurons contribute to the intensity with which rats interact with the external environment, both when the interaction is "spontaneous" and when the interaction is provoked by threatening or salient environmental events. PMID:25324552

  3. Reduced pancreatic protein secretion in response to cholecystokinin (CCK) in the obese Zucker rat correlates with a reduced receptor capacity for CCK

    SciTech Connect

    Praissman, M.; Izzo, R.S.

    1986-08-01

    Pancreatic membrane receptors for cholecystokinin (CCK) in obese and nonobese Zucker rats were compared with the use of a biologically active (/sup 125/I)iodo-CCK-8 radioprobe. Membrane homogenates from obese rats bound half the amount of radioligand in 2 h as did membranes from lean rats (specifically bound, 7.0% vs. 14.0%; P less than 0.001). The reduced binding in membranes from obese rats did not result from kinetic effects or radioligand degradation; similar rates of association and dissociation of (/sup 125/I)iodo-CCK-8 were obtained in membrane preparations from both, and no differences were found in the extent of radioligand degradation in the two membrane preparations. These differences also did not reflect an effect of cell size, as pancreatic acinar cells from obese and nonobese rats had about the same perimeters (24.6 and 26.3 micron, respectively) and areas (30.1 and 34.2 micron 2, respectively). Scatchard-type plots of competitive displacement data for CCK-binding sites on pancreatic membranes from both genotypes were curvilinear and were analyzed by a two-site binding model. The Kd values for both the high (0.56 vs. 0.45 nM) and low (9.0 vs. 14 nM) affinity sites on membranes from nonobese and obese rats, respectively, were the same (P greater than 0.1), whereas the capacities for CCK in the high (365 vs. 165 fmol/mg protein) and low (1020 vs. 360 fmol/mg protein) affinity regions were significantly different (P less than 0.025). This difference in CCK receptor capacity was reflected by a reduced pancreatic protein secretory response in the obese rat. After injections of 40, 80, 160, and 320 ng CCK/kg BW, total pancreatic protein secretion in nonobese rats increased 5, 12, 19, and 21 times above basal levels, whereas the same doses caused 2-, 6-, 12-, and 13-fold increases in obese rats.

  4. The alginate reduce the postprandial glycaemic response by forming a gel with dietary calcium in the stomach of the rat.

    PubMed

    Ohta, A; Taguchi, A; Takizawa, T; Adachi, T; Kimura, S; Hashizume, N

    1997-01-01

    Soluble dietary fibers include an alginate which reduces the postprandial glycaemic response. We speculated that the cause of the reduction of alginate on the glycaemic response is the gel formation of alginate with dietary calcium in the stomach. The aim of the present study was to confirm our hypothesis and to examine the effect of the sugar composition of alginates on the glycaemic response and the effect of continuous feeding of alginate-containing diet to rats. Diabetic rats were made by injecting streptozotocin (STZ) intravenously. These rats were fed 5 g of the experimental diet with or without sodium alginate and with or without calcium after overnight fasting. In the rats fed the diet containing both alginate and calcium, the postprandial glycaemic response was lower than in the rats fed other diets and gastric contents were retained as gel form. Three beta-d-mannuronic acid (M) to alpha-l-guluronic acid (G) (ratios (M/G 0.5, 1.3, 2.1) of alginates were not associated with the acute glycaemic response in STZ rats. Then, we fed normal rats with an alginate-free or one of three respective alginate-containing diets for 4 weeks. During the first 2 weeks of the feeding period, the total amount of food intake of rats fed the G-rich alginate diet was smaller than that of rats in the other dietary groups. Moreover, the weight of the dorsal abdominal adipose tissue of rats given the G-rich alginate diet was the lowest among the dietary groups. We conclude that the reductive effect of alginate feeding on the postprandial glycaemic response was not caused only by their inherent viscosity, but also by gel formation with dietary calcium in the stomach. Moreover, it is necessary to pay attention to the M/G ratio of alginates for estimating their physiological effect. PMID:9119615

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

    PubMed

    Burch, Sara H

    2014-09-01

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

  6. Naftazone reduces glutamate cerebro spinal fluid levels in rats and glutamate release from mouse cerebellum synaptosomes.

    PubMed

    Mattei, C; Molgó, J; Joseph, X; Israel, M; Bloy, C

    1999-08-27

    It is well known that an excessive release of glutamate in the mammalian brain plays a major role in several neurological diseases. Naftazone (Etioven) is a currently used vasoprotectant drug that is metabolized in humans by reduction and glucuronidation. In the present study naftazone was found to decrease glutamate levels in the cerebro spinal fluid (CSF) of rats treated for 15 days, as determined by a chemiluminescent glutamate assay reaction. Naftazone and its glucuronide derivative also reduced respectively spontaneous and high K+-evoked glutamate release from mouse cerebellum synaptosomes. It is likely that naftazone and its glucuronide metabolite contribute in vivo to decrease glutamate levels in the CSF through their inhibitory actions on glutamate release. PMID:10507699

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  9. Chandelier cartridges in the prefrontal cortex are reduced in isolation reared rats.

    PubMed

    Bloomfield, Claire; French, Sarah J; Jones, Declan N C; Reavill, Charlie; Southam, Eric; Cilia, Jackie; Totterdell, Susan

    2008-08-01

    Chandelier neurons are a subset of parvalbumin containing cortical interneurons characterised by their preferential targeting of the axon initial segments of pyramidal neurons. They have been the focus of recent interest after evidence that the arrays of boutons are reduced in the prefrontal cortex of schizophrenic patients, post mortem. Since one chandelier neuron may innervate the axon initial segments of several hundred pyramidal neurons, it is hypothesized that their special connectivity might facilitate synchronisation of cortical outputs and play a key role in working memory. Disruption in their function is therefore thought to play a potentially important role in cortically associated symptoms of schizophrenia. Using the isolation rearing animal model of schizophrenia, we examined immunolabelling for GABA-transporter 1, a marker of chandelier cartridges. We show that the numbers of arrays of chandelier axons are reduced by 36% in the ventral prelimbic cortex of isolation-reared rats, compared with their socially-housed litter mates. This mimics findings in the PFC of schizophrenic patients where GAT-1-positive cartridges are reduced by 40% and is the first study to demonstrate changes in chandelier cartridges in an animal model of schizophrenia. PMID:18512213

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-10-01

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

  12. Inhibition of angiotensin-converting enzyme reduces susceptibility of hypertrophied rat myocardium to ventricular fibrillation.

    PubMed

    Shimada, Yasuyuki; Gunasegaram, Suba; Yokoyama, Hiroyuki; Avkiran, Metin

    2002-11-01

    Left ventricular (LV) hypertrophy increases susceptibility to reperfusion arrhythmias and the angiotensin-converting enzyme inhibitor, ramipril, may reduce that susceptibility via regression of LV hypertrophy. Rats (n=12 per group) were subjected to abdominal aortic constriction (AC) or sham-operation (SH) and from 3 to 6 weeks after surgery, 3 AC groups received ramipril (0.01, 0.1, or 1 mg/kg per day p.o.) while the SH and 1 AC group received vehicle. Six weeks after surgery (ie after 3 weeks of treatment), the hearts were excised and subjected to independent Langendorf perfusion of left and right coronary beds. The left coronary bed was then subjected to ischemia (7 min) and reperfusion (5 min). Hypertrophied hearts from the vehicle AC group showed a significant increase in the incidence of reperfusion-induced ventricular fibrillation (VF) compared with control hearts from the SH group (92%* vs 33%: *p<0.05); this difference was abolished by ramipril (42%, 50%, and 42%, at 0.01, 0.1, or 1 mg/kg per day, respectively). The LV weight/body weight ratio was significantly increased in all AC groups (regardless of ramipril treatment) relative to the SH group. At the cellular level, myocyte length was significantly increased in the vehicle AC group, but was normalized by ramipril treatment (1 mg/kg per day). At the molecular level, atrial natriuretic factor (ANF) mRNA expression was also significantly increased in the vehicle AC group, but was again normalized by ramipril treatment (1 mg/kg per day). In conclusion, short-term treatment with ramipril reduced susceptibility to severe ventricular arrhythmias in hypertrophied rat hearts. This protection was achieved in the absence of a significant reduction in LV weight, but was accompanied by regression of myocyte hypertrophy, as reflected by reductions in cell size and ANF expression. PMID:12419938

  13. Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus?

    PubMed Central

    Chen, Zhihong; He, Yaqiang; Song, Chengjun; Dong, Zhijun; Su, Zhejun; Xue, Jingfeng

    2012-01-01

    In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway.

  14. Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus.

    PubMed

    Chen, Zhihong; He, Yaqiang; Song, Chengjun; Dong, Zhijun; Su, Zhejun; Xue, Jingfeng

    2012-01-25

    In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway. PMID:25767499

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

    SciTech Connect

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

    2007-11-03

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

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

    PubMed

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

    2014-11-16

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

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

    USGS Publications Warehouse

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Dietary docosahexaenoic acid supplementation reduces SERCA Ca(2+) transport efficiency in rat skeletal muscle.

    PubMed

    Fajardo, Val Andrew; Bombardier, Eric; Irvine, Thomas; Metherel, Adam H; Stark, Ken D; Duhamel, Todd; Rush, James W E; Green, Howard J; Tupling, A Russell

    2015-04-01

    Docosahexaenoic acid (DHA) can reduce the efficiency and increase the energy consumption of Na(+)/K(+)-ATPase pump and mitochondrial electron transport chain by promoting Na(+) and H(+) membrane permeability, respectively. In skeletal muscle, the sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) pumps are major contributors to resting metabolic rate. Whether DHA can affect SERCA efficiency remains unknown. Here, we examined the hypothesis that dietary supplementation with DHA would reduce Ca(2+) transport efficiency of the SERCA pumps in skeletal muscle. Total lipids were extracted from enriched sarcoplasmic reticulum (SR) membranes that were isolated from red vastus lateralis skeletal muscles of rats that were either fed a standard chow diet supplemented with soybean oil or supplemented with DHA for 8 weeks. The fatty acid composition of total SR membrane lipids and the major phospholipid species were determined using electrospray ionization mass spectrometry (ESI-MS). After 8 weeks of DHA supplementation, total SR DHA content was significantly elevated (control, 4.1±1.0% vs. DHA, 9.9±1.7%; weight percent of total fatty acids) while total arachidonic acid was reduced (control, 13.5±0.4% vs. DHA-fed, 9.4±0.2). Similar changes in these fatty acids were observed in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, altogether indicating successful incorporation of DHA into the SR membranes post-diet. As hypothesized, DHA supplementation reduced SERCA Ca(2+) transport efficiency (control, 0.018±0.0002 vs. DHA-fed, 0.014±0.0009) possibly through enhanced SR Ca(2+) permeability (ionophore ratio: control, 2.8±0.2 vs. DHA-fed, 2.2±0.3). Collectively, our results suggest that DHA may promote skeletal muscle-based metabolism and thermogenesis through its influence on SERCA. PMID:25772907

  20. Forelimb preferences in quadrupedal marsupials and their implications for laterality evolution in mammals

    PubMed Central

    2013-01-01

    Background Acquisition of upright posture in evolution has been argued to facilitate manual laterality in primates. Owing to the high variety of postural habits marsupials can serve as a suitable model to test whether the species-typical body posture shapes forelimb preferences in non-primates or this phenomenon emerged only in the course of primate evolution. In the present study we aimed to explore manual laterality in marsupial quadrupeds and compare them with the results in the previously studied bipedal species. Forelimb preferences were assessed in captive grey short-tailed opossum (Monodelphis domestica) and sugar glider (Petaurus breviceps) in four different types of unimanual behaviour per species, which was not artificially evoked. We examined the possible effects of sex, age and task, because these factors have been reported to affect motor laterality in placental mammals. Results In both species the direction of forelimb preferences was strongly sex-related. Male grey short-tailed opossums showed right-forelimb preference in most of the observed unimanual behaviours, while male sugar gliders displayed only a slight, not significant rightward tendency. In contrast, females in both species exhibited consistent group-level preference of the left forelimb. We failed to reveal significant differences in manual preferences between tasks of potentially differing complexity: reaching a stable food item and catching live insects, as well as between the body support and food manipulation. No influence of subjects’ age on limb preferences was found. Conclusions The direction of sex-related differences in the manual preferences found in quadrupedal marsupials seems to be not typical for placental mammals. We suggest that the alternative way of interhemispheric connection in absence of corpus callosum may result in a fundamentally distinct mechanism of sex effect on limb preferences in marsupials compared to placentals. Our data confirm the idea that non-primate mammals differ from primates in sensitivity to task complexity. Comparison of marsupial species studied to date indicate that the vertical body orientation and the bipedalism favor the expression of individual– and population–level forelimb preferences in marsupials much like it does in primates. Our findings give the first evidence for the effect of species-typical posture on the manual laterality in non-primate mammals. PMID:23497116

  1. The distal forelimb musculature in aquatic and terrestrial turtles: phylogeny or environmental constraints?

    PubMed Central

    Abdala, Virginia; Manzano, Adriana S; Herrel, Anthony

    2008-01-01

    We compared the muscular anatomy of the distal front limb in terrestrial and aquatic chelonians to test whether observed differences between the two groups are associated with their divergent lifestyles and locomotor modes. Given the different use of the forelimb in the two environments (body support and propulsion on land vs. mainly propulsion in water) we expected that: (1) aquatic and terrestrial turtles would show differences in their muscular anatomy, with aquatic species having more individualized muscle bundles to allow for the complex forearm movements observed during swimming, and (2) that terrestrial turtles would have more robust muscles to support their body weight against gravity. To address these questions, we examined the forelimb myology and associated tissues in six aquatic or semi-aquatic turtles (Phyrnops hilarii, Podocnemis unifilis, Trachemys scripta, Sacalia bealei, Cuora amboinensis and Mauremys caspica) and six terrestrial or semi-terrestrial turtles (Geochelone chilensis, Testudo graeca, Cuora galbinifrons, Glyptemys insculpta, Terrapene carolina and Rhinoclemmys pulcherrima). This paper describes the general structure of the forelimb musculature in all species, and quantifies muscle masses in those species with more than five specimens available (Ph. hilarii, Po. unifilis and Ge. chilensis). The general structure of the forelimb muscles in the strictly terrestrial species Ge. chilensis and Tes. graeca was found to be notably different from the pattern of the aquatic and semi-aquatic species examined, showing a distinct fusion of the different muscular bodies. Ter. carolina also show a distinctly terrestrial pattern, but a less extensive tendon development. R. pulcherrima and Gl. insculpta were found to be morphologically intermediate; in the geoemydids the strictly terrestrial bauplan never appears. Quantitative differences in the robustness or mass of the distal forelimb muscles were also observed for the species investigated, supporting our prediction that the extensor muscles are more robust in terrestrial turtles. However, in contrast to our expectations, not only the extensor muscles of the distal forelimb (which are crucial in providing both body support and propulsion), but all muscles acting around the wrist were found to be heavier in terrestrial turtles. PMID:19172731

  2. Post-stroke protection from maladaptive effects of learning with the non-paretic forelimb by bimanual home cage experience in C57BL/6 mice

    PubMed Central

    Kerr, Abigail L.; Wolke, Malerie L.; Bell, Jared A.; Jones, Theresa A.

    2013-01-01

    Behavioral experience, in the form of skilled limb use, has been found to impact the structure and function of the central nervous system, affecting post-stroke behavioral outcome in both adaptive and maladaptive ways. Learning to rely on the less-affected, or non-paretic, body side is common following stroke in both humans and rodent models. In rats, it has been observed that skilled learning with the non-paretic forelimb following ischemic insult leads to impaired or delayed functional recovery of the paretic limb. Here we used a mouse model of focal motor cortical ischemic injury to examine the effects of non-paretic limb training following unilateral stroke. In addition, we exposed some mice to increased bimanual experience in the home cage following stroke to investigate the impact of coordinated dexterous limb use on the non-paretic limb training effect. Our results confirmed that skilled learning with the non-paretic limb impaired functional recovery following stroke in C56BL/6 mice, as it does in rats. Further, this effect was avoided when the skill learning of the non-paretic limb was coupled with increased dexterous use of both forelimbs in the home cage. These findings further establish the mouse as an appropriate model in which to study the neural mechanisms of recovery following stroke and extend previous findings to suggest that the dexterous coordinated use of the paretic and non-paretic limb can promote functional outcome following injury. Keywords: experience-dependent plasticity, learned nonuse, motor cortex, motor rehabilitation, stroke PMID:23756140

  3. Decreased Bdnf expression and reduced social behavior in periadolescent rats following prenatal stress.

    PubMed

    Berry, Alessandra; Panetta, Pamela; Luoni, Alessia; Bellisario, Veronica; Capoccia, Sara; Andrea Riva, Marco; Cirulli, Francesca

    2015-04-01

    Prenatal stress (PNS) is a risk factor for the development of neuropsychiatric disorders. This study was aimed at assessing, in a rodent model, changes in gene expression profiles and behavioral output as a result of PNS, during periadolescence, a critical developmental period for the onset of psychopathology. Social behavior was studied in a standardized social interaction paradigm and the expression of Brain-Derived Neurotrophic Factor (Bdnf), a marker of neuronal plasticity, and of inhibitory and excitatory mechanisms (Na(+) -K(+) -2Cl(-) and K(+) -Cl(-) cotransporters ratio, NKCC1/KCC2) was analyzed. Results indicate that PNS reduced Bdnf transcripts while increasing the NKCC1/KCC2 ratio, primarily in the hippocampus. In the prefrontal cortex, changes in Bdnf were found to be gender-dependent. These effects were accompanied by reduced levels of affiliative and investigative social behaviors. Interestingly, interaction with non-stressed subjects was able to improve sociality in PNS rats suggesting that the social environment could be exploited for therapeutic intervention. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 57: 365-373, 2015. PMID:25783782

  4. Procyanidins in Theobroma cacao Reduce Plasma Cholesterol Levels in High Cholesterol-Fed Rats

    PubMed Central

    Osakabe, Naomi; Yamagishi, Megumi

    2009-01-01

    We evaluated the effect of cacao procyanidins (CP) on plasma lipid levels in high cholesterol-fed rats. Animals were divided into 4 groups, and each group was fed on either a normal diet, high cholesterol diet (HCD) containing 1% cholesterol (HCD without CP), HCD with 0.5% (HCD with 0.5% CP) or 1.0% CP (HCD with 1.0% CP) for 4 weeks. Plasma cholesterol level was significantly higher in the HCD without CP group than the normal diet group (p<0.01). Supplementation of CP significantly decreased plasma cholesterol (p<0.01) to levels similar to those of the normal diet group. The liver cholesterol and triglyceride levels in all HCD groups were significantly higher (p<0.01), but 1.0% CP feeding significantly reduced this increase. Fecal excretion of neutral sterol and triglyceride was significantly increased in all HCD groups (p<0.01), and the excreted amounts tended to be higher in the HCD with CP groups. The procyanidins dose-dependently reduced micellar solubility of cholesterol and this activity increased with increasing molecular weight. These results suggest that one of the mechanisms of CP to lower plasma cholesterol is inhibition of intestinal absorption of cholesterol. PMID:19794919

  5. Procyanidins in Theobroma cacao Reduce Plasma Cholesterol Levels in High Cholesterol-Fed Rats.

    PubMed

    Osakabe, Naomi; Yamagishi, Megumi

    2009-09-01

    We evaluated the effect of cacao procyanidins (CP) on plasma lipid levels in high cholesterol-fed rats. Animals were divided into 4 groups, and each group was fed on either a normal diet, high cholesterol diet (HCD) containing 1% cholesterol (HCD without CP), HCD with 0.5% (HCD with 0.5% CP) or 1.0% CP (HCD with 1.0% CP) for 4 weeks. Plasma cholesterol level was significantly higher in the HCD without CP group than the normal diet group (p<0.01). Supplementation of CP significantly decreased plasma cholesterol (p<0.01) to levels similar to those of the normal diet group. The liver cholesterol and triglyceride levels in all HCD groups were significantly higher (p<0.01), but 1.0% CP feeding significantly reduced this increase. Fecal excretion of neutral sterol and triglyceride was significantly increased in all HCD groups (p<0.01), and the excreted amounts tended to be higher in the HCD with CP groups. The procyanidins dose-dependently reduced micellar solubility of cholesterol and this activity increased with increasing molecular weight. These results suggest that one of the mechanisms of CP to lower plasma cholesterol is inhibition of intestinal absorption of cholesterol. PMID:19794919

  6. Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring.

    PubMed

    Camarillo, Ignacio G; Clah, Leon; Zheng, Wei; Zhou, Xuanzhu; Larrick, Brienna; Blaize, Nicole; Breslin, Emily; Patel, Neal; Johnson, Diamond; Teegarden, Dorothy; Donkin, Shawn S; Gavin, Timothy P; Newcomer, Sean

    2014-11-01

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea. Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared with pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention. PMID:24950432

  7. Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats

    PubMed Central

    Sun, Yu; Yang, Rui; Zhong, Ji-gen; Fang, Feng; Jiang, Jin-jin; Liu, Ming-yao; Lu, Jian

    2009-01-01

    Introduction Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. Methods Rats were intravenously injected with oleic acid (OA) to induce ALI and 30 minutes later they were divided into five groups: model (injury only), PPS aerosol (PPS-aer), saline aerosol (saline-aer), PPS instillation (PPS-inst), and saline instillation (Saline-Inst). Blood gases, lung histology, and protein and TNF-? concentrations in the bronchoalveolar lavage fluid (BALF) were examined. Results The PPS aerosol particles were less than 2.0 ?m in size as determined by a laser aerosol particle counter. Treatment of animals with a PPS aerosol significantly increased the phospholipid content in the BALF, improved lung function, reduced pulmonary oedema, decreased total protein and TNF-? concentrations in BALF, ameliorated lung injury and improved animal survival. These therapeutic effects are similar to those seen in the PPS-inst group. Conclusions This new method of PPS aerosolisation combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing. It is an effective, simple and safe method of administering an exogenous surfactant. PMID:19257907

  8. The anti-craving drug acamprosate reduces c-fos expression in rats undergoing ethanol withdrawal.

    PubMed

    Putzke, J; Spanagel, R; Tölle, T R; Zieglgänsberger, W

    1996-12-12

    Acamprosate (Ca salt of N-acetylhomotaurine) is a novel anti-craving substance which a double-blind placebo-controlled study has proven to be therapeutically useful in the prevention of relapses in weaned alcoholics. In the present study the expression of the immediate-early gene c-fos in rat hippocampal and cerebellar neurons was used to monitor the modulatory effect of acamprosate on neuronal excitability during ethanol withdrawal. Several hybridization techniques were employed to investigate the effect of acamprosate on c-fos expression. Acamprosate (200 mg/kg; intraperitoneally) reduced the elevated c-fos mRNA levels in the hippocampus and the cerebellum following 24 h of ethanol withdrawal, or the application of the convulsant pentylenetetrazole. The effect of ethanol withdrawal on c-fos expression was more pronounced in the cerebellum than in the hippocampus. In the hippocampus (CA1) and the cerebellum acamprosate alone induced a significant increase in c-fos expression in drug-naive animals. Only in the hippocampus did co-administration of pentylenetetrazole during ethanol withdrawal induce a further increase in c-fos expression. The present findings support the notion that acamprosate elicits its preventive effect on relapse by reducing the hyperexcitability of central neurons during withdrawal, following long-term ethanol consumption. PMID:8982717

  9. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    PubMed

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by nicotine and they implicate dopaminergic systems both in conditioned approach as well as the incentive-promoting effects of nicotine. PMID:25230311

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats.

    PubMed

    Reckelhoff, J F; Zhang, H; Granger, J P

    1998-01-01

    Studies were performed in intact male and female, gonadectomized male and female, and gonadectomized female rats given testosterone for 5 weeks to investigate the role played by testosterone in altered blood pressure control and pressure-natriuresis in male SHR. Serum testosterone levels reached a peak at 12 weeks of age in intact male SHR. Systolic blood pressure, measured weekly from 5 to 20 weeks of age, was similar between groups until 12 weeks of age when blood pressure became higher in males (195+/-3 mm Hg) than in females (168+/-3 mm Hg) or males castrated at 4 weeks (173+/-4 mm Hg). At 17 to 19 weeks direct measurement of arterial pressure in anesthetized rats confirmed that mean arterial pressure was higher in male (182+/-1 mm Hg) than in female (159+/-2 mm Hg) and castrated male SHR (159+/-2 mm Hg). In addition, testosterone (5 mg in Silastic pellets, SC for 5 weeks) administered to ovariectomized (ovx+T) females caused arterial pressure to increase by mm 11% (175+/-2 mm Hg), which was significantly higher than in intact female, castrated male, or untreated ovariectomized (ovx) female SHR (158+/-2 mm Hg). Acute pressure-natriuresis was blunted in male SHR compared with females, castrated males, or ovx females, in which this relationship was similar. Pressure-natriuresis was also blunted in ovx+T females as found in intact male SHR. These data support the hypothesis that male sex hormones contribute to the exacerbation of hypertension in SHR by reducing pressure-natriuresis. PMID:9453341

  14. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

    PubMed Central

    Shu, Liang; Su, Jingjing; Jing, Lingyan; Huang, Ying; Di, Yu; Peng, Lichao; Liu, Jianren

    2014-01-01

    Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy. PMID:24778886

  15. Aniseed oil increases glucose absorption and reduces urine output in the rat.

    PubMed

    Kreydiyyeh, Sawsan Ibrahim; Usta, Julnar; Knio, Khuzama; Markossian, Sarine; Dagher, Shawky

    2003-12-19

    Anise (Pimpinella anisum) has been used as a traditional aromatic herb in many drinks and baked foods because of the presence of volatile oils in its fruits commonly known as seeds. Hot water extracts of the seeds have been used also in folk medicine for their diuretic and laxative effect, expectorant and anti-spasmodic action, and their ability to ease intestinal colic and flatulence. The aim of this work was to study the effect of aniseed oil on transport processes through intestinal and renal epithelia and determine its mechanism of action. The essential oils were extracted from the seeds by hydrodistillation and analyzed by gas chromatography. Aniseed oil enhanced significantly glucose absorption from the rat jejunum and increased the Na+-K+ ATPase activity in a jejunal homogenate in a dose dependent manner. The oil, however, exerted no effect on water absorption from the colon and did not alter the activity of the colonic Na+-K+ ATPase. When added to drinking water, it reduced the volume of urine produced in the rat and increased the activity of the renal Na+-K+ ATPase even at extremely low concentrations. It was concluded that aniseed oil increases glucose absorption by increasing the activity of the Na+-K+ ATPase and consequently the sodium gradient needed for the sugar transport. Its anti-diuretic effect is also mediated through a similar mechanism in the kidney whereby a stimulation of the Na+-K+ pump increases tubular sodium reabsorption and osmotic water movement. The colonic Na+-K+ ATPase was however, resistant to the oil. PMID:14623036

  16. 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...

  17. Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.

    PubMed

    Hassler, Shayne N; Johnson, Kathia M; Hulsebosch, Claire E

    2014-11-01

    Chronic neuropathic pain is a common consequence of spinal cord injury (SCI), develops over time and negatively impacts quality of life, often leading to substance abuse and suicide. Recent evidence has demonstrated that reactive oxygen species (ROS) play a role in contributing to neuropathic pain in SCI animal models. This investigation examines four compounds that reduce ROS and the downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and tirilazad, and tests if these compounds can reduce nocioceptive behaviors in chronic SCI animals. Apocynin and 4-oxo-tempo significantly reduced abnormal mechanical hypersensitivity measured in forelimbs and hindlimbs in a model of chronic SCI-induced neuropathic pain. Thus, compounds that inhibit ROS or lipid peroxidation products can be used to ameliorate chronic neuropathic pain. We propose that the application of compounds that inhibit reactive oxygen species (ROS) and related downstream molecules will also reduce the behavioral measures of chronic neuropathic pain. Injury or trauma to nervous tissue leads to increased concentrations of ROS in the surviving tissue. Further damage from ROS molecules to dorsal lamina neurons leads to membrane excitability, the physiological correlate of chronic pain. Chronic pain is difficult to treat with current analgesics and this research will provide a novel therapy for this disease. PMID:25051888

  18. Reduced protein oxidation in Wistar rats supplemented with marine ?3 PUFAs.

    PubMed

    Méndez, Lucía; Pazos, Manuel; Gallardo, José M; Torres, Josep L; Pérez-Jiménez, Jara; Nogués, Rosa; Romeu, Marta; Medina, Isabel

    2013-02-01

    The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on protein redox states from plasma, kidney, skeletal muscle, and liver were investigated in Wistar rats. Dietary fish oil groups were compared with animals fed soybean and linseed oils, vegetable oils enriched in ?6 linoleic acid (LA; 18:2) and ?3 ?-linolenic acid (ALA; 18:3), respectively. Fish oil treatments were effective at reducing the level of total fatty acids in plasma and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Albumin was found to be the most carbonylated protein in plasma for all dietary groups, and its oxidation level was significantly modulated by dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed the lowest oxidation score for plasma albumin, followed in increasing order of carbonylation by 1:2 <2:1 ? linseed < soybean. Oxidation patterns of myofibrillar skeletal muscle proteins and cytosolic proteins from kidney and liver also indicated a protective effect on proteins for the fish oil treatments, the 1:1 ratio exhibiting the lowest protein oxidation scores. The effect of fish oil treatments at reducing carbonylation on specific proteins from plasma (albumin), skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3-?-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights the efficiency of dietary fish oil at reducing in vivo oxidative damage of proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids ?3 ALA and ?6 LA, and such antioxidant activity may differ among different fish oil sources because of variations in EPA/DHA content. PMID:23159545

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

    PubMed Central

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

    2014-01-01

    While hypothermia (HT) is the standard-of-care for neonates with hypoxic ischemic injury (HII), the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24?hr after HII with HT (32?; n?=?18) or normothermia (NT, 35?; n?=?15). Outcomes included magnetic resonance imaging (MRI), neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72?hr post-HII). Lesion volumes (24?hr) were reduced in HT pups (total 74%, p?reduced interleukin-1? (IL-1?) at all time points (p?reduces total and penumbral lesion volumes (at 24 and 48?hr), potentially by decreasing IL-1? without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72?hr post-HII when IL-1? levels remained low suggests that after rewarming, mechanisms unrelated to IL-1? expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury. PMID:25424430

  20. The effect of perineural anesthesia on infrared thermographic images of the forelimb digits of normal horses

    PubMed Central

    Holmes, Layne C.; Gaughan, Earl M.; Gorondy, Denise A.; Hogge, Steve; Spire, Mark F.

    2003-01-01

    Infrared thermography is an imaging modality gaining popularity as a diagnostic aid in the evaluation of equine lameness. Anecdotal reports of skin hyperthermia induced by local anesthesia, detected by thermography, have been made; however, no controlled studies have been reported. The purpose of this study was to examine the effects of perineural anesthesia on infrared thermographic images of the forelimb digits in normal horses. After environmental acclimation, infrared thermographs were made at intervals of 0, 5, 10, 15, 30, and 45 min from administration of mepivacaine hydrochloride or phosphate buffered saline in 6 adult horses with no clinical evidence of abnormality of the forelimb digits. The mean limb surface temperatures were compared by 2-factor ANOVA. Results indicated no significant difference between treatments, time after injection, or an interaction of time and treatment. Infrared thermographic imaging apparently can be performed within 45 min of perineural mepivacaine hydrochloride anesthesia without risk of artifactual changes in limb surface temperature. PMID:12757130

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

    PubMed

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

    2014-09-01

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

  2. Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats

    PubMed Central

    Yoo, Hyun-Wook; Chang, Moon-Jeong

    2014-01-01

    BACKGROUND/OBJECTIVES Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. MATERIALS/METHODS In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). RESULTS Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-? estradiol concentrations in young rats, and 17-? estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. CONCLUSIONS Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women. PMID:25324934

  3. Hip extensor EMG and forelimb/hind limb weight support asymmetry in primate quadrupeds.

    PubMed

    Larson, Susan G; Stern, Jack T

    2009-03-01

    Higher weight support on the hind limb than forelimb is among the distinctive characteristics of primate quadrupeds. Although often assumed to be due to a more posteriorly positioned whole body center of mass, there are little data to support such a difference. Reynolds (1985. Am J Phys Anthropol 67:335-349) notes that the distribution of forces on the limbs can also be influenced by average limb posture, but suggests that this effect is too small to account for the asymmetry in weight support observed in primates. Instead, he proposes that high hind limb forces are brought about by an active process of shifting weight off the forelimbs and onto the hind limbs through use of hind limb retractors. In this study, we use video records of walking animals to explore the degree to which average limb posture in primates and other quadrupedal mammals deviates from vertical, and use electromyography to test Reynolds' model of hind limb retractor activity and posterior weight shift. The limb posture results indicate that primate forelimbs oscillate about a vertical or slightly retracted axis, and though the hind limbs are slightly protracted, the magnitude of deviation from vertical is too small to have a major effect on weight support distribution. The electromyographic results reveal higher levels of hip extensor activity in antipronograde primates that bear a higher proportion of weight on their hind limbs. This lends support to Reynolds' suggestion that some primates use muscles to actively shift weight onto hind limbs to relieve stresses on forelimbs less well structured for weight support. PMID:18924163

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    PubMed Central

    2012-01-01

    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. PMID:22639913

  6. Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

    PubMed

    Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

    2014-03-01

    The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P???0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P???0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats. PMID:24249159

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

    PubMed

    Fujiwara, Shin-ichi; Hutchinson, John R

    2012-07-01

    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

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

    PubMed Central

    Fujiwara, Shin-ichi; Hutchinson, John R.

    2012-01-01

    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

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

    PubMed Central

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

    2009-01-01

    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

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

    PubMed

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

    2009-12-01

    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

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

    PubMed Central

    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.

    2013-01-01

    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

  12. Asymmetric dimethylarginine reduced erythrocyte deformability in streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Zhi-Chun Yang; Ke Xia; Li Wang; Su-Jie Jia; Dai Li; Zhe Zhang; Shen Deng; Xiao-Hong Zhang; Han-Wu Deng; Yuan-Jian Li

    2007-01-01

    To investigate the effect of asymmetric dimethylarginine on erythrocyte deformability in streptozotocin-induced diabetic rats, a single intraperitoneal injection of streptozotocin (STZ, 65 mg\\/kg) in male Sprague–Dawley rats was carried out to induce diabetes and normal erythrocytes were incubated with asymmetric dimethylarginine or aortic rings from diabetic rats in the presence of l-arginine or vitamin E. We found that erythrocyte deformability was

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

    Microsoft Academic Search

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

    2010-01-01

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

  14. Astaxanthin-enriched-diet reduces blood pressure and improves cardiovascular parameters in spontaneously hypertensive rats.

    PubMed

    Monroy-Ruiz, José; Sevilla, María-Ángeles; Carrón, Rosalía; Montero, María-José

    2011-01-01

    The aim of this study was to investigate the effects of astaxanthin-enriched diet on blood pressure, cardiac hypertrophy, both vascular structure and function and superoxide ((*)O(2-)) production in spontaneously hypertensive rats (SHR). Twelve-week-old SHR were treated for 8 weeks with an astaxanthin-enriched diet (75 or 200mg/kg body weight per day). Systolic blood pressure was monitorized periodically during the study by the tail cuff method. At the end of the study animals were sacrificed and heart, kidneys and aorta were removed. Left ventricular weight/body weight ratio was used as left ventricular hypertrophy index (LVH). Vascular function and structure were studied in conductance (aortic rings) and resistance (renal vascular bed) arteries. Also (*)O(2-) production was evaluated by lucigenin-enhanced chemiluminescence. Systolic blood pressure was lower in astaxanthin-treated groups than the control group from the first week of treatment, and LVH was significantly reduced. Astaxanthin improved endothelial function on resistance arteries, but had no effect on aorta. These effects were accompanied by a decrease in oxidative stress and improvements in NO bioavailability. Taken together, these results show that diet supplemented with astaxanthin has beneficial effects on hypertension, by decreasing blood pressure values, improving cardiovascular remodeling and oxidative stress. PMID:20868751

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

    PubMed

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

    2013-08-25

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

  16. KGF-2 targets alveolar epithelia and capillary endothelia to reduce high altitude pulmonary oedema in rats

    PubMed Central

    She, Jun; Goolaerts, Arnaud; Shen, Jun; Bi, Jing; Tong, Lin; Gao, Lei; Song, Yuanlin; Bai, Chunxue

    2012-01-01

    High altitude pulmonary oedema (HAPE) severely affects non-acclimatized individuals and is characterized by alveolar flooding with protein- rich oedema as a consequence of blood-gas barrier disruption. Limited choice for prophylactic treatment warrants effective therapy against HAPE. Keratinocyte growth factor-2 (KGF-2) has shown efficiency in preventing alveolar epithelial cell DNA damages in vitro. In the current study, the effects of KGF-2 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of HAPE. We found that pre-treatment with KGF-2 (5 mg/kg) significantly decreased mortality, improved oxygenation and reduced lung wet-to-dry weight ratio by preventing alveolar-capillary barrier disruption demonstrated by histological examination and increasing alveolar fluid clearance up to 150%. In addition, KGF-2 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10-fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of KGF-2 on inhibition of endothelial cell apoptosis, preservation of alveolar-capillary barrier integrity and promotion of pulmonary oedema absorption in HAPE. Thus, KGF-2 may represent a potential drug candidate for the prevention of HAPE. PMID:22568566

  17. Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat.

    PubMed

    Gudbjarnason, S; el-Hage, A N; Whitehurst, V E; Simental, F; Balazs, T

    1987-11-01

    The fatty acid composition of phospholipids and triglycerides in heart muscle was examined in normal and alloxan-diabetic male Wistar rats. In diabetes the major phospholipids, phosphatidyl choline and phosphatidyl ethanolamine, showed significant changes in fatty acid composition, whereas cardiolipin and phosphatidyl serine + phosphatidyl inositol did not show marked changes in fatty acid profile. In phosphatidyl choline there was a significant diminution in arachidonic acid, 20 : 4(n-6) and palmitic acid, 16 : 0, and a corresponding increase in linoleic acid, 18 : 2(n-6), and stearic acid, 18 : 0. In phosphatidyl ethanolamine the level of 20 : 4(n-6) was significantly reduced. The diabetic heart had normal levels of individual phospholipids, whereas the triglycerides were increased by 90% and contained significantly higher levels of 18 : 2(n-6). The results confirm that diabetes is associated with a diminution in fatty acid desaturation, affecting the fatty acid composition of phosphatidyl choline in particular. These changes may be relevant to development of atherosclerosis and relative resistance to catecholamine-induced cardiac necrosis in diabetes. PMID:3437462

  18. Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

    PubMed Central

    O'Brien, Emmanuelle Simon; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël

    2011-01-01

    A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0?g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5–40?mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10?mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20?mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10?mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment. PMID:21430652

  19. Subcellular localization and distribution of the reduced folate carrier in normal rat tissues.

    PubMed

    Hinken, M; Halwachs, S; Kneuer, C; Honscha, W

    2011-01-01

    The reduced folate carrier (Rfc1; Slc19a1) mediated transport of reduced folates and antifolate drugs such as methotrexate (MTX) play an essential role in physiological folate homeostasis and MTX cancer chemotherapy. As no systematic reports are as yet available correlating Rfc1 gene expression and protein levels in all tissues crucial for folate and antifolate uptake, storage or elimination, we investigated gene and protein expression of rat Rfc1 (rRfc1) in selected tissues. This included the generation of a specific anti-rRfc1 antibody. Rabbits were immunised with isolated rRfc1 peptides producing specific anti-rRfc1 antiserum targeted to the intracellular C-terminus of the carrier. Using RT-PCR analysis, high rRfc1 transcript levels were detected in colon, kidney, brain, thymus, and spleen. Moderate rRfc1 gene expression was observed in small intestine, liver, bone marrow, lung, and testes whereas transcript levels were negligible in heart, skeletal muscle or leukocytes. Immunohistochemical analyses revealed strong carrier expression in the apical membrane of tunica mucosa epithelial cells of small intestine and colon, in the brush-border membrane of choroid plexus epithelial cells or in endothelial cells of small vessels in brain and heart. Additionally, high rRfc1 protein levels were localized in the basolateral membrane of renal tubular epithelial cells, in the plasma membrane of periportal hepatocytes, and sertoli cells of the testes. Taken together, our results demonstrated that rRfc1 is expressed almost ubiquitously but to very different levels. The predominant tissue distribution supports the essential role of Rfc1 in physiological folate homeostasis. Moreover, our results may contribute to understand antifolate pharmacokinetics and selected organ toxicity associated with MTX chemotherapy. PMID:21556118

  20. Subcellular localization and distribution of the reduced folate carrier in normal rat tissues

    PubMed Central

    Hinken, M.; Halwachs, S.; Kneuer, C.; Honscha, W.

    2011-01-01

    The reduced folate carrier (Rfc1; Slc19a1) mediated transport of reduced folates and antifolate drugs such as methotrexate (MTX) play an essential role in physiological folate homeostasis and MTX cancer chemotherapy. As no systematic reports are as yet available correlating Rfc1 gene expression and protein levels in all tissues crucial for folate and antifolate uptake, storage or elimination, we investigated gene and protein expression of rat Rfc1 (rRfc1) in selected tissues. This included the generation of a specific anti-rRfc1 antibody. Rabbits were immunised with isolated rRfc1 peptides producing specific anti-rRfc1 antiserum targeted to the intracellular C-terminus of the carrier. Using RT-PCR analysis, high rRfc1 transcript levels were detected in colon, kidney, brain, thymus, and spleen. Moderate rRfc1 gene expression was observed in small intestine, liver, bone marrow, lung, and testes whereas transcript levels were negligible in heart, skeletal muscle or leukocytes. Immunohistochemical analyses revealed strong carrier expression in the apical membrane of tunica mucosa epithelial cells of small intestine and colon, in the brush-border membrane of choroid plexus epithelial cells or in endothelial cells of small vessels in brain and heart. Additionally, high rRfc1 protein levels were localized in the basolateral membrane of renal tubular epithelial cells, in the plasma membrane of periportal hepatocytes, and sertoli cells of the testes. Taken together, our results demonstrated that rRfc1 is expressed almost ubiquitously but to very different levels. The predominant tissue distribution supports the essential role of Rfc1 in physiological folate homeostasis. Moreover, our results may contribute to understand antifolate pharmacokinetics and selected organ toxicity associated with MTX chemotherapy. PMID:21556118

  1. Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during endotoxaemia in the rat

    PubMed Central

    Chang, Alice Y W; Chan, Julie Y H; Chou, Jimmy L J; Li, Faith C H; Dai, Kuang-Yu; Chan, Samuel H H

    2006-01-01

    The rostral ventrolateral medulla (RVLM) is the origin of a ‘life-and-death’ signal that reflects central cardiovascular regulatory failure during brain stem death. Using an experimental endotoxaemia model, we evaluated the hypothesis that the 60 kDa heat shock protein 60 (HSP60) reduces cardiovascular fatality during brain stem death via an anti-apoptotic action in the RVLM. In Sprague-Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg?1). Pretreatment with a microinjection of actinomycin D or cycloheximide into bilateral RVLM significantly blunted this HSP60 increase, whereas real-time PCR showed progressive augmentation of hsp60 mRNA. Intriguingly, superimposed on the augmented expression was a progressive decline in mitochondrial, or elevation in cytosolic, HSP60 in ventrolateral medulla. Loss-of-function manipulations in the RVLM using anti-HSP60 antiserum or antisense hsp60 oligonucleotide exacerbated mortality by potentiating the cardiovascular depression during experimental endotoxaemia, alongside intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone-associated DNA fragments or augmented cytochrome c–caspase-3 cascade of apoptotic signalling in the RVLM. Immunoprecipitation coupled with immunoblot analysis further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl-2 during endotoxaemia, alongside a dissociation of the cytosolic HSP60–Bcl-2 complex. We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome c–caspase-3 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl-2. PMID:16675490

  2. Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.

    PubMed Central

    Kang, J X; Xiao, Y F; Leaf, A

    1995-01-01

    Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 microM eicosapentaenoic acid for 2-5 min markedly increased the strength of the depolarizing current required to elicit an action potential (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of excitability (from 525 ms to 1225 ms, delta = 700 +/- 212, P < 0.05). These changes were due to an increase in the threshold for action potential (from -52 mV to -43 mV, delta = 9 +/- 3, P < 0.05) and a more negative resting membrane potential (from -52 mV to -57 mV, delta = 5 +/- 1, P < 0.05). There was a progressive prolongation of intervals between spontaneous action potentials and a slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids--including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid, and its nonmetabolizable analog eicosatetraynoic acid, but neither the monounsaturated oleic acid nor the saturated stearic acid--had similar effects. The effects of the fatty acids could be reversed by washing with fatty acid-free bovine serum albumin. These results show that free polyunsaturated fatty acids can reduce membrane electrical excitability of heart cells and provide an electrophysiological basis for the antiarrhythmic effects of these fatty acids. PMID:7732020

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  4. Acid fibroblast growth factor reduces rat intestinal mucosal damage caused by ischemia-reperfusion insult

    PubMed Central

    Chen, Wei; Fu, Xiao-Bing; Ge, Shi-Li; Sun, Tong-Zhu; Li, Wen-Juan; Sheng, Zhi-Yong

    2005-01-01

    AIM: To detect the effects of acid fibroblast growth factor (aFGF) on apoptosis and proliferation of intestinal epithelial cells in differentiation or proliferation status to explore the protective mechanisms of aFGF. METHODS: Wistar rats were randomly divided into sham-operated control group (C, n?=?6), intestinal ischemia group (I, n?=?6), aFGF treatment group (A, n?=?48) and intestinal ischemia-reperfusion group (R, n?=?48). Apoptosis of intestinal mucosal cells was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) technique. Proliferating cell nuclear antigen (PCNA) protein expression and distribution were detected with immunohistochemical method. Plasma levels of D-lactate were determined with modified Brandts method. RESULTS: In A group, administration of exogenous aFGF could improve intestinal histological structure and decrease plasma D-lactate levels at 2-12 h after the reperfusion compared with R group. The apoptotic rates and PCNA protein expressions were not increased until 2 h after reperfusion and were maximal at 12 h. After reperfusion for 2-12 h, the apoptotic rates were gradually augmented along the length of jejunal crypt-villus units. Administration of aFGF could significantly reduce the apoptotic response at 2-12 h after reperfusion (P<0.05). Apoptosis rates in villus and crypt epithelial cells in A group at 12 h after reperfusion were (62.5±5.5)% and (73.2±18.6)% of those in R group, respectively. Treatment of aFGF could apparently induce protein expression of PCNA in intestinal mucosal cells of A group compared with R group during 2-12 h after reperfusion (P<0.05). There were approximately 1.3- and 1.5-times increments of PCNA expression levels in villus and crypt cells in A group at 12 h after reperfusion compared with R group, respectively. CONCLUSION: Intestinal I/R insult could lead to histological structure change and apoptotic rate increment. The protective effects of aFGF against ischemia/reperfusion in rat intestinal mucosa might be partially due to its ability to inhibit ischemia/reperfusion-induced apoptosis and to promote cell proliferation of crypt cells and villus epithelial cells. PMID:16425419

  5. Chitosan oligosaccharides prevented retinal ischemia and reperfusion injury via reduced oxidative stress and inflammation in rats.

    PubMed

    Fang, I-Mo; Yang, Chung-May; Yang, Chang-Hao

    2015-01-01

    The purpose of the present study was to investigate the protective effect and mechanism of chitosan oligonucleotides (COS) on retinal ischemia and reperfusion (I/R) injury. Rats pretreated with PBS, low-dose COS (5 mg/kg), or high-dose COS (10 mg/kg) were subjected to retinal ischemia by increasing their intraocular pressure to 130 mm Hg for 60 min. The protective effect of COS was evaluated by determining the electroretinograms (ERGs), morphology of the retina, and survival of retinal ganglion cells (RGCs). The oxidative damage was determined by imuunohistochemistry and ELISA, respectively. The expressions of inflammatory mediators (TNF-?, IL-1?, MCP-1, iNOS, ICAM-1) and apoptotic-related proteins (p53, Bax, Bcl-2) were quantified by PCR and Western blots. The detection of NF-?B p65 in the retina was performed by immunofluorescence. The protein levels of I?B and phosphorylated mitogen-activated protein kinases [MAPK; viz. extracellular signal-regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK) and p38] and the NF-?B/DNA binding ability were assessed by Western blot analysis and EMSA. We found that pretreatment with COS, especially a high dosage, effectively ameliorated the I/R-induced reduction of the b-wave ratio in ERGs and the retinal thickness and the survival of RGCs at 24 h. COS decreased the expression of inflammatory mediators, p53 and Bax, increasing Bcl-2 expression and thereby reducing retinal oxidative damage and the number of apoptotic cells. More importantly, COS attenuated I?B degradation and p65 presence in the retina, thus decreasing NF-?B/DNA binding activity after I/R. In addition, COS decreased the phosphorylation levels of JNK and ERK but increased the phosphorylation level of p38. Pretreatment with p38 inhibitor (SB203580) abolished the protective effect of COS on retinal oxidative damage, as indicated by increased retinal 8-OHdG stains, and significantly increased the expression of inflammatory mediators (TNF-?, MCP-1, iNOS, ICAM-1) in I/R-injured rats. In conclusion, COS prevented retinal I/R injury through its inhibition of oxidative stress and inflammation. These effects were achieved by blocking the activation of NF-?B, JNK, and ERK but promoting the activation of p38 activation. PMID:25479043

  6. Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats

    PubMed Central

    Tu, Huiyin; Zhang, Libin; Tran, Thai P.; Muelleman, Robert L.; Li, Yu-Long

    2010-01-01

    Voltage-gated sodium (Nav) channels are responsible for initiation and propagation of action potential in the neurons. To explore the mechanisms for chronic heart failure (CHF)-induced baroreflex dysfunction, we measured the expression and current density of Nav channel subunits (Nav1.7, Nav1.8, and Nav1.9) in the aortic baroreceptor neurons and investigated the role of Nav channels on aortic baroreceptor neuron excitability and baroreflex sensitivity in sham and CHF rats. CHF was induced by left coronary artery ligation. The development of CHF (6–8 weeks after the coronary ligation) was confirmed by hemodynamic and morphological characteristics. Immunofluorescent data indicated that Nav1.7 was expressed in A-type (myelinated) and C-type (unmyelinated) nodose neurons but Nav1.8 and Nav1.9 were expressed only in C-type nodose neurons. Real-time RT-PCR and western blot data showed that CHF reduced mRNA and protein expression levels of Nav channels in nodose neurons. In addition, using the whole cell patch-clamp technique, we found that Nav current density and cell excitability of the aortic baroreceptor neurons were lower in CHF rats than that in sham rats. Aortic baroreflex sensitivity was blunted in anesthetized CHF rats, compared with that in sham rats. Furthermore, Nav channel activator (rATX II, 100 nM) significantly enhanced Nav current density and cell excitability of aortic baroreceptor neurons and improved aortic baroreflex sensitivity in CHF rats. These results suggest that reduced expression and activation of the Nav channels is involved in the attenuation of baroreceptor neuron excitability, which subsequently contributes to the impairment of baroreflex in CHF state. PMID:20857502

  7. Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure

    PubMed Central

    Damment, Stephen; Secker, Roger; Shen, Victor; Lorenzo, Victor; Rodriguez, Mariano

    2011-01-01

    Background. Lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD–mineral and bone disorder (CKD–MBD). Methods. Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion. Results. Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis. Conclusions. Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD–MBD in a rat model of CRF. PMID:21098011

  8. Reduced susceptibility to azoxymethane-induced aberrant crypt foci formation and colon cancer in growth hormone deficient rats

    PubMed Central

    Carroll, Robert E.; Goodlad, Robert A.; Poole, Aleksandra J.; Tyner, Angela L.; Robey, R. Brooks; Swanson, Steven M.; Unterman, Terry G.

    2010-01-01

    Objectives To evaluate the role of GH in colon carcinogenesis, we examined the formation of aberrant crypt foci (ACFs) and tumor development in wild type (WT) and GH-deficient, spontaneous dwarf rats (SDRs) exposed to the carcinogen azoxymethane (AOM). Design ACF were quantified by stereomicroscopy and tumor number and weights were recorded for each animal. Cell proliferation was measured by vincristine metaphase arrest, flow cytometry, and bromode-oxyuridine (BrdU) incorporation. Apoptosis was measured by TUNEL staining and cleaved caspase-3 immunohistochemistry. IGF-I was measured by radioimmunoassay (RIA). Hexokinase activity was measured by spectrophotometric assay. PARP cleavage, and IGF-IR, and p27kip/cip expression were measured by Western blotting. Results ACFs detected by stereomicroscopy were markedly reduced (~85%) in SDRs vs. WT rats at 10, 25, and 28 weeks after AOM. Tumor incidence, number, and weight also were reduced in SDR vs. WT animals. AOM treatment increased cell proliferation in the distal colon (where tumors occur) of WT rats but not SDRs, and these changes corresponded to increased ACF and tumor formation. Apoptosis rates were similar in AOM-treated WT and SDRs. Alterations in serum IGF-I levels may contribute to differences in the proliferative response to AOM and decreased ACF formation in SDR vs. WT rats. Conclusions We conclude that early neoplastic lesions (ACFs) were reduced in GH-deficient animals. This effect corresponds with differences in AOM-induced proliferation, but not apoptosis. These data indicate that GH is required for the full effect of AOM on colon ACF and tumor development, and that the SDR rat is a promising model for studies regarding the role of GH/IGF system in the initiation and promotion of colon cancer. PMID:19406679

  9. EFFECT OF ATRAZINE ADMINISTRATION ON SPONTANEOUS AND EVOKED CEREBELLAR ACTIVITY IN THE RAT

    Microsoft Academic Search

    MARIA VITTORIA PODDA; FRANCA DERIU; ANTONIO SOLINAS; MARIA PIERA DEMONTIS; MARIA VITTORIA VARONI; ALESSANDRO SPISSU; VITTORIO ANANIA; EUSEBIO TOLU

    1997-01-01

    The effect of atrazine oral administration on cerebellar forelimb projection area was studied in rats in vivo. Rats acutely treated with atrazine (100 mg kg–1, BW) showed a significant decrease in spontaneous Purkinje cell firing rate. Atrazine also decreased the cerebellar potentials evoked by electrical stimulation of the ipsilateral radial nerve, affecting mostly the response to climbing fiber input. These

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

    PubMed

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

    1998-10-19

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Bemis, J C; Seegal, R F

    1999-01-01

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

  13. Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

    PubMed

    Tanaka, Kunihiko; Gotoh, Taro M; Awazu, Chihiro; Morita, Hironobu

    2005-12-01

    To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs. PMID:16081624

  14. Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats.

    PubMed

    Furuyashiki, Takashi; Ogawa, Rui; Nakayama, Yoko; Honda, Kazuhisa; Kamisoyama, Hiroshi; Takata, Hiroki; Yasuda, Michiko; Kuriki, Takashi; Ashida, Hitoshi

    2013-09-01

    Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet-induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation. PMID:24034574

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

    PubMed

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

    2013-06-01

    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. PMID:23551946

  16. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

    PubMed

    Hamouda, N N; Sydorenko, V; Qureshi, M A; Alkaabi, J M; Oz, M; Howarth, F C

    2015-02-01

    In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 ± 25 mg/dl, n = 21) compared to Controls (98 ± 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 ± 2.28 %, n = 37) and STZ (76.58 ± 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 ± 5.35 %, n = 16) myocytes compared to Controls (92.01 ± 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats. PMID:25351341

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

    Microsoft Academic Search

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

    2001-01-01

    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 =

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

    PubMed Central

    Saha, Shyamali; Prakash, Satya

    2014-01-01

    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

  19. Lactobacillus plantarum NDC 75017 alleviates the learning and memory ability in aging rats by reducing mitochondrial dysfunction

    PubMed Central

    PENG, XINYAN; MENG, JIONG; CHI, TAO; LIU, PENG; MAN, CHAOXIN; LIU, SHAOMIN; GUO, YING; JIANG, YUJUN

    2014-01-01

    The aim of the present study was to investigate the protective effect of Lactobacillus plantarum NDC 75017 on D-galactose (D-gal)-induced mitochondrial dysfunction in the rat cerebral cortex. Fifty rats were randomly divided into five groups (n=10 in each group). The rats in the aging model group were subcutaneously injected with 100 mg/kg D-gal and those in the protective groups were additionally orally administered L. plantarum NDC 75017 at doses of 1×108, 1×109 or 1×1010 CFU/100 mg body weight/day, respectively. The control rats were administrated an equal volume of the vehicle. Following continuous treatment for seven weeks, the learning and memory abilities and mitochondrial ultrastructure, function and adenosine triphosphate (ATP) levels were examined. The results showed that the learning and memory abilities and mitochondrial levels of ATP were significantly decreased in the D-gal-induced aging model group compared with those in the control group (P<0.01). In addition, marked changes in the mitochondrial functions and ultrastructure were observed between the groups. Seven weeks of L. plantarum NDC 75017 and D-gal coadministration significantly improved the learning and memory abilities of the rats compared with the D-gal-induced aging model group. Furthermore, the combination regime significantly improved the mitochondrial ultrastructure and functions, including the mitochondrial respiratory chain, mitochondrial membrane potential and mitochondrial permeability transition. The results revealed that the L. plantarum NDC 75017 was able to alleviate learning and memory injuries in aging rats by reducing the mitochondrial dysfunction induced by D-gal. PMID:25371742

  20. Lactobacillus plantarum NDC 75017 alleviates the learning and memory ability in aging rats by reducing mitochondrial dysfunction.

    PubMed

    Peng, Xinyan; Meng, Jiong; Chi, Tao; Liu, Peng; Man, Chaoxin; Liu, Shaomin; Guo, Ying; Jiang, Yujun

    2014-12-01

    The aim of the present study was to investigate the protective effect of Lactobacillus plantarum NDC 75017 on D-galactose (D-gal)-induced mitochondrial dysfunction in the rat cerebral cortex. Fifty rats were randomly divided into five groups (n=10 in each group). The rats in the aging model group were subcutaneously injected with 100 mg/kg D-gal and those in the protective groups were additionally orally administered L. plantarum NDC 75017 at doses of 1×10(8), 1×10(9) or 1×10(10) CFU/100 mg body weight/day, respectively. The control rats were administrated an equal volume of the vehicle. Following continuous treatment for seven weeks, the learning and memory abilities and mitochondrial ultrastructure, function and adenosine triphosphate (ATP) levels were examined. The results showed that the learning and memory abilities and mitochondrial levels of ATP were significantly decreased in the D-gal-induced aging model group compared with those in the control group (P<0.01). In addition, marked changes in the mitochondrial functions and ultrastructure were observed between the groups. Seven weeks of L. plantarum NDC 75017 and D-gal coadministration significantly improved the learning and memory abilities of the rats compared with the D-gal-induced aging model group. Furthermore, the combination regime significantly improved the mitochondrial ultrastructure and functions, including the mitochondrial respiratory chain, mitochondrial membrane potential and mitochondrial permeability transition. The results revealed that the L. plantarum NDC 75017 was able to alleviate learning and memory injuries in aging rats by reducing the mitochondrial dysfunction induced by D-gal. PMID:25371742

  1. Selective Angiotensin II Receptor Antagonism Reduces Insulin Resistance in Obese Zucker Rats

    Microsoft Academic Search

    Erik J. Henriksen; Stephan Jacob; Tyson R. Kinnick; Mary K. Teachey; Michael Krekler

    Effects of oral administration of the angiotensin II receptor antagonist (selective AT 1-subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in

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

    Microsoft Academic Search

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

    1992-01-01

    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

  3. Dietary PUFA supplements reduce memory deficits but not CA1 ischemic injury in rats.

    PubMed

    Plamondon, Hélène; Roberge, Marie-Claude

    2008-10-20

    The purpose of the present study was to examine the impact of nutritional supplementation with essential omega 3 and 6 fatty acids on CA1 neuronal death and recovery of functional impairments following global ischemia. Groups of Wistar male rats were randomly assigned to four experimental conditions determined by the consumed diet and surgical condition. Rats either received a standard diet (SD; Purina 5012) or a 15% PUFA supplemented diet (FO+CO) prepared by adding 11.5% (w/w) fish oil from menhaden fish and 3.5% corn oil to standard rat chow. Diet conditions were initiated in 30 day old rats and maintained for an 18-week period (pre- and post-surgery). Sham or 8-min global ischemic surgeries occurred during the 13th feeding week and behavioral testing took place following reperfusion for an additional 4 weeks, after which all rats were euthanized. Our findings revealed significant loss of pyramidal CA1 neurons 31 days post ischemia in ischemic as compared to sham-operated rats but no difference between ischemic animals fed the SD or PUFA supplemented diets. In the radial arm maze, SD ischemic rats took longer time to complete the task and made significantly more working memory errors than PUFA ischemic and sham-operated animals. Independent of the diet, ischemic animals appeared less anxious in the elevated plus maze, spending considerably more time in the open arms as compared to sham-operated rats. Taken together, these results suggest that fish oil supplemented diet exerts beneficial effect on ischemia-induced spatial memory deficits despite protective effects on CA1 hippocampal neurons. PMID:18700150

  4. Green Tea Polyphenols Reduce Body Weight in Rats by Modulating Obesity-Related Genes

    Microsoft Academic Search

    Chuanwen Lu; Wenbin Zhu; Chwan-Li Shen; Weimin Gao

    2012-01-01

    Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12\\/group) of Sprague Dawley (SD) female rats were tested, including the control group

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

    Microsoft Academic Search

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

    2005-01-01

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

  6. Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6-OHDA dopamine-depleted (hemi-Parkinson analogue) rats.

    PubMed

    Metz, G A; Farr, T; Ballermann, M; Whishaw, I Q

    2001-07-01

    L-dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether L-dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of L-dopa in reversing the motor deficits in rats, we administered 6-OHDA unilaterally to produce hemi-Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6-OHDA treatment and did not improve after chronic L-dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by L-dopa treatment. These findings are the first in the rat to suggest that whereas L-dopa has a general activating effect on the rat's whole-body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function. PMID:11488946

  7. Patterns of spatio-temporal correlations in the neural activity of the cat motor cortex during trained forelimb movements.

    PubMed

    Ghosh, Soumya; Putrino, David; Burro, Bianca; Ring, Alexander

    2009-06-01

    In order to study how neurons in the primary motor cortex (MI) are dynamically linked together during skilled movement, we recorded simultaneously from many cortical neurons in cats trained to perform a reaching and retrieval task using their forelimbs. Analysis of task-related spike activity in the MI of the hemisphere contralateral to the reaching forelimb (in identified forelimb or hindlimb representations) recorded through chronically implanted microwires, was followed by pairwise evaluation of temporally correlated activity in these neurons during task performance using shuffle corrected cross-correlograms. Over many months of recording, a variety of task-related modulations of neural activities were observed in individual efferent zones. Positively correlated activity (mainly narrow peaks at zero or short latencies) was seen during task performance frequently between neurons recorded within the forelimb representation of MI, rarely within the hindlimb area of MI, and never between forelimb and hindlimb areas. Correlated activity was frequently observed between neurons with different patterns of task-related activity or preferential activity during different task elements (reaching, feeding, etc.), and located in efferent zones with dissimilar representation as defined by intracortical microstimulation. The observed synchronization of action potentials among selected but functionally varied groups of MI neurons possibly reflects dynamic recruitment of network connections between efferent zones during skilled movement. PMID:19697261

  8. Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart

    PubMed Central

    Sattari, Saeed; Dryden, William F; Eliot, Lise A; Jamali, Fakhreddin

    2003-01-01

    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. PMID:12839868

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

    PubMed Central

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

    2011-01-01

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

  10. Sitagliptin reduces hyperglycemia and increases satiety hormone secretion more effectively when used with a novel polysaccharide in obese Zucker rats.

    PubMed

    Reimer, Raylene A; Grover, Gary J; Koetzner, Lee; Gahler, Roland J; Juneja, Prateek; Lyon, Michael R; Wood, Simon

    2012-10-01

    The novel polysaccharide (NPS) PolyGlycopleX (PGX) has been shown to reduce glycemia. Pharmacological treatment with sitagliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, also reduces glycemia by increasing glucagon-like peptide-1 (GLP-1). Our objective was to determine if using NPS in combination with sitagliptin reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than either treatment alone. Male ZDF rats were randomized to: 1) cellulose/vehicle [control (C)]; 2) NPS (5% wt:wt)/vehicle (NPS); 3) cellulose/sitagliptin [10 mg/(kg · d) (S)]; or 4) NPS (5%) + S [10 mg/(kg · d) (NPS+S)]. Glucose tolerance, adiposity, satiety hormones, and mechanisms related to DPP4 activity and hepatic and pancreatic histology were examined. A clinically relevant reduction in hyperglycemia occurred in the rats treated with NPS+S (P = 0.001) compared with NPS and S alone. Blood glucose, measured weekly in fed and feed-deprived rats and during an oral glucose tolerance test, was lower in the NPS+S group compared with all other groups (all P = 0.001). At wk 6, glycated hemoglobin was lower in the NPS+S group than in the C and S (P = 0.001) and NPS (P = 0.06) groups. PGX (P = 0.001) and S (P = 0.014) contributed to increased lean mass. Active GLP-1 was increased by S (P = 0.001) and GIP was increased by NPS (P = 0.001). Plasma DPP4 activity was lower in the NPS+S and S groups than in the NPS and C groups (P = 0.007). Insulin secretion and ?-cell mass was increased with NPS (P < 0.05). NPS alone reduced LDL cholesterol and hepatic steatosis (P < 0.01). Independently, NPS and S improve several metabolic outcomes in ZDF rats, but combined, their ability to markedly reduce glycemia suggests they may be a promising dietary/pharmacological co-therapy for type 2 diabetes management. PMID:22915295

  11. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats[S

    PubMed Central

    Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K.; Pacheco-López, Gustavo; Turnbull, Andrew V.; Langhans, Wolfgang; Mansouri, Abdelhak

    2013-01-01

    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. PMID:23449193

  12. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

    PubMed

    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

    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

  13. Photoacoustic detection of functional responses in the motor cortex of awake behaving monkey during forelimb movement

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Zhang, Hongyu; Cheney, Paul D.; Yang, Xinmai

    2012-11-01

    Photoacoustic (PA) imaging was applied to detect the neuronal activity in the motor cortex of an awake, behaving monkey during forelimb movement. An adult macaque monkey was trained to perform a reach-to-grasp task while PA images were acquired through a 30-mm diameter implanted cranial chamber. Increased PA signal amplitude results from an increase in regional blood volume and is interpreted as increased neuronal activity. Additionally, depth-resolved PA signals enabled the study of functional responses in deep cortical areas. The results demonstrate the feasibility of utilizing PA imaging for studies of functional activation of cerebral cortex in awake monkeys performing behavioral tasks.

  14. The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis.

    PubMed

    Abu-Daya, Anita; Nishimoto, Satoko; Fairclough, Lynn; Mohun, Timothy J; Logan, Malcolm P O; Zimmerman, Lyle B

    2011-01-15

    While limb regeneration has been extensively studied in amphibians, little is known about the initial events in limb formation in metamorphosing anurans. The small secreted integrin ligand nephronectin (npnt) is necessary for development of the metanephros in mouse. Although expressed in many tissues, its role in other developmental processes is not well-studied. Here we show that a transgene insertion that disrupts this gene ablates forelimb formation in Xenopus tropicalis. Our results suggest a novel role for integrin signalling in limb development, and represent the first insertional phenotype to be cloned in amphibians. PMID:20977901

  15. Preclinical efficacy of sodium narcistatin to reduce inflammation and joint destruction in rats with adjuvant-induced arthritis.

    PubMed

    Lubahn, Cheri; Schaller, Jill A; Shewmacker, Eric; Wood, Carlo; Bellinger, Denise L; Byron, Donna; Melody, Noeleen; Pettit, George R; Lorton, Dianne

    2012-12-01

    Current therapies for the treatment of rheumatoid arthritis (RA) do not work for all patients, can lose efficacy over time, and can have significant side effects. The discovery of new, effective therapies for RA remains an unmet medical need. The Amaryllidaceae isocarbostyril narciclasine was previously shown to prophylactically reduce paw swelling in rats with adjuvant-induced arthritis (AA). In this study, the efficacy of sodium narcistatin (SNS), a water-soluble cyclic phosphate pro-drug of narciclasine, was assessed in AA rats for anti-inflammatory and bone-sparing properties after disease onset. AA rats were given daily intraperitoneal injections of SNS (1.75, 3.5, or 5 mg/kg/day, in 500 ?l sterile endotoxin-free saline) or saline from disease onset through severe disease stages. Footpad widths and radiographic scoring were used as indicators of inflammation and joint destruction, respectively. Ex vivo cytokine production by peripheral blood mononuclear cells (PMBC), splenocytes, and draining lymph node (DLN) cells were determined using ELISAs. SNS treatment dose-dependently reduced joint inflammation (~70%) and bone loss (~50%) compared with AA controls. SNS treatment also reduced spleen weight (without affecting body weight), pro-inflammatory cytokine production by PMBC, splenocytes, and DLN cells, and site-dependently altered T-helper (Th)1-/Th2-type and anti-inflammatory cytokine profiles. SNS dramatically reduces inflammation and has bone-sparing properties, possibly by reducing immune cell pro-inflammatory cytokine production. Our findings support the development of SNS as a therapeutic for RA. PMID:22159913

  16. Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury.

    PubMed

    Thyfault, John P; Rector, R Scott; Uptergrove, Grace M; Borengasser, Sarah J; Morris, E Matthew; Wei, Yongzhong; Laye, Matt J; Burant, Charles F; Qi, Nathan R; Ridenhour, Suzanne E; Koch, Lauren G; Britton, Steve L; Ibdah, Jamal A

    2009-04-15

    Fatty liver has been linked to low aerobic fitness, but the mechanisms are unknown. We previously reported a novel model in which rats were artificially selected to be high capacity runners (HCR) and low capacity runners (LCR) that in a sedentary condition have robustly different intrinsic aerobic capacities. We utilized sedentary HCR/LCR rats (generation 17; max running distance equalled 1514 +/- 91 vs. 200 +/- 12 m for HCR and LCR, respectively) to investigate if low aerobic capacity is associated with reduced hepatic mitochondrial oxidative capacity and increased susceptibility to hepatic steatosis. At 25 weeks of age, LCR livers displayed reduced mitochondrial content (reduced citrate synthase activity and cytochrome c protein) and reduced oxidative capacity (complete palmitate oxidation in hepatic mitochondria (1.15 +/- 0.13 vs. 2.48 +/- 1.1 nm g(-1) h, P < 0.0001) and increased peroxisomal activity (acyl CoA oxidase and catalase activity) compared to the HCR. The LCR livers also displayed a lipogenic phenotype with higher protein content of both sterol regulatory element binding protein-1c and acetyl CoA carboxylase. These differences were associated with hepatic steatosis in the LCR including higher liver triglycerides (6.00 +/- 0.71 vs. 4.20 +/- 0.39 nmol g(-1), P = 0.020 value), >2-fold higher percentage of hepatocytes associated with lipid droplets (54.0 +/- 9.2 vs. 22.0 +/- 3.5%, P = 0.006), and increased hepatic lipid peroxidation compared to the HCR. Additionally, in rats aged to natural death, LCR livers had significantly greater hepatic injury (fibrosis and apoptosis). We provide novel evidence that selection for low intrinsic aerobic capacity causes reduced hepatic mitochondrial oxidative capacity that increases susceptibility to both hepatic steatosis and liver injury. PMID:19237421

  17. Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury

    PubMed Central

    Thyfault, John P; Rector, R Scott; Uptergrove, Grace M; Borengasser, Sarah J; Morris, E Matthew; Wei, Yongzhong; Laye, Matt J; Burant, Charles F; Qi, Nathan R; Ridenhour, Suzanne E; Koch, Lauren G; Britton, Steve L; Ibdah, Jamal A

    2009-01-01

    Fatty liver has been linked to low aerobic fitness, but the mechanisms are unknown. We previously reported a novel model in which rats were artificially selected to be high capacity runners (HCR) and low capacity runners (LCR) that in a sedentary condition have robustly different intrinsic aerobic capacities. We utilized sedentary HCR/LCR rats (generation 17; max running distance equalled 1514 ± 91 vs. 200 ± 12 m for HCR and LCR, respectively) to investigate if low aerobic capacity is associated with reduced hepatic mitochondrial oxidative capacity and increased susceptibility to hepatic steatosis. At 25 weeks of age, LCR livers displayed reduced mitochondrial content (reduced citrate synthase activity and cytochrome c protein) and reduced oxidative capacity (complete palmitate oxidation in hepatic mitochondria (1.15 ± 0.13 vs. 2.48 ± 1.1 nm g?1 h, P < 0.0001) and increased peroxisomal activity (acyl CoA oxidase and catalase activity) compared to the HCR. The LCR livers also displayed a lipogenic phenotype with higher protein content of both sterol regulatory element binding protein-1c and acetyl CoA carboxylase. These differences were associated with hepatic steatosis in the LCR including higher liver triglycerides (6.00 ± 0.71 vs. 4.20 ± 0.39 nmol g?1, P= 0.020 value), >2-fold higher percentage of hepatocytes associated with lipid droplets (54.0 ± 9.2 vs. 22.0 ± 3.5%, P= 0.006), and increased hepatic lipid peroxidation compared to the HCR. Additionally, in rats aged to natural death, LCR livers had significantly greater hepatic injury (fibrosis and apoptosis). We provide novel evidence that selection for low intrinsic aerobic capacity causes reduced hepatic mitochondrial oxidative capacity that increases susceptibility to both hepatic steatosis and liver injury. PMID:19237421

  18. Reduced expression of nogo-a leads to motivational deficits in rats.

    PubMed

    Enkel, Thomas; Berger, Stefan M; Schönig, Kai; Tews, Björn; Bartsch, Dusan

    2014-01-01

    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. PMID:24478657

  19. Reduced Expression of Nogo-A Leads to Motivational Deficits in Rats

    PubMed Central

    Enkel, Thomas; Berger, Stefan M.; Schönig, Kai; Tews, Björn; Bartsch, Dusan

    2014-01-01

    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. PMID:24478657

  20. The utility of the phosphate binder, ferric citrate hydrate (JTT-751), about phosphorus absorption-reducing effect in normal rats.

    PubMed

    Matsuo, Akira; Iida, Akio; Tanimoto, Minako; Matsushita, Mutsuyoshi; Miyamoto, Ken-ichi

    2014-09-01

    Hyperphosphatemia is a risk factor for arterial calcification contributing to the high-cardiovascular mortality in patients with chronic kidney disease (CKD). Ferric citrate hydrate (JTT-751) is being developed as a treatment for hyperphosphatemia with chronic renal failure and has shown a serum phosphorus-lowering effect in CKD patients. In this study, we evaluated the combination effect of JTT-751 with the phosphorus absorption-reducing effect of calcium carbonate and compared phosphorus absorption-reducing efficacy between three phosphate binders including JTT-751. Normal rats were fed a diet containing either 1% calcium carbonate, 1% JTT-751 or 1% JTT-751 with 1% calcium carbonate, for 7 days. Both 1% calcium carbonate and 1% JTT-751 alone reduced urinary phosphorus excretion, and the combined treatment reduced it more than each single-treatment, without clearly influencing calcium or iron-metabolism. Next, normal rats were fed a diet containing either 0.3, 1 and 3% lanthanum carbonate or 2.3% JTT-751, for 7 days. Either 3% lanthanum carbonate or 2.3% JTT-751 reduced urinary phosphorus excretion. Finally, we compared the reduced amount of urinary phosphorus excretion per dose of compound, of which JTT-751 is comparable to that of calcium carbonate and is greater than that of the lanthanum carbonate. In conclusion, JTT-751 showed an additive effect on the phosphorus absorption-reducing effect of calcium carbonate without influencing calcium- and iron-metabolism, and had a phosphorus absorption-reducing efficacy comparable to or greater than other existing phosphate binders. PMID:24975675

  1. Pratensein ameliorates ?-amyloid-induced cognitive impairment in rats via reducing oxidative damage and restoring synapse and BDNF levels.

    PubMed

    Liang, Chunhong; Tan, Shimei; Huang, Quanfang; Lin, Jun; Lu, Zhongpeng; Lin, Xing

    2015-04-10

    This study was designed to investigate the protective effect of pratensein against cognitive impairment induced by amyloid beta (1-42) (A?1-42) in rats. A?1-42 peptide was injected bilaterally in the hippocampus of rat. Next, pratensein was administered orally for 3 weeks. Our findings demonstrated that treatment with pratensein ameliorated learning and memory deficits in A?1-42 rat model of AD. Pratensein treatment significantly attenuated neuronal degeneration and apoptosis in hippocampus. Moreover, the over-expression in IL-1? and TNF-? as well as the extensive astrogliosis and microgliosis in hippocampus induced by A?1-42 were significantly reduced following administration of pratensein. Concomitantly, pratensein treatment significantly suppressed the activation of NF-?B in hippocampus. In addition, pratensein was able to increase the levels of synaptophysin and brain-derived neurotrophic factor (BDNF). These results indicate that pratensein could significantly ameliorate A?1-42-induced spatial learning and memory impairment through reducing neuroinflammation via inhibition of glial activation and NF-?B activation, and restoring synapse and BDNF levels, suggesting that administration of pratensein could likely provide a therapeutic approach for AD. PMID:25748315

  2. Mild hypothermia reduces expression of Fas/FasL and MMP-3 after cerebral ischemia-reperfusion in rats

    PubMed Central

    Zhao, Jingkun; Duan, Shurong; Zhou, Jinxia; Sun, Ruihong; Zhang, Liming; Wang, Desheng

    2014-01-01

    Objective(s): To investigate the effects of local mild hypothermia on the expression of Fas, FasL and MMP-3 after cerebral ischemia-reperfusion in rats. Materials and Methods: Male Wistar rats were divided into sham-operated group (Sham), normothermia group (NT), and hypothermia group (HT). MCAO/R model was established by Longa’s method, and reperfusion was allowed after 2 hr occlusion. Mild hypothermia (33±0.5°C) for 6 hr was initiated at the start of reperfusion. Immunohistochemistry was performed to determine expression Fas, FasL, and MMP-3. Results: Infarct volume was reduced in the hypothermia group (18.43±4.23%) compared with the normothermia group (24.76±5.76%) (P<0.05). In mild hypothermia group, numbers of Fas-positive and MMP-3 positive cells were significantly less than those of normothermia group (P<0.05). Neurological functional scores of mild hypothermia were significantly improved (P<0.05). Conclusion: Mild hypothermia decreases infarct volume after cerebral ischemia-reperfusion, reduces Fas and MMP-3 expression, but increases FasL in cerebral ischemia-reperfusion rats. PMID:25140208

  3. Valproate prevents dysregulation of spinal glutamate and reduces the development of hypersensitivity in rats after peripheral nerve injury

    PubMed Central

    Yoshizumi, Masaru; Eisenach, James. C.; Hayashida, Ken-ichiro

    2013-01-01

    The present study examined whether the histone deacetylase inhibitor valproate prevents down-regulation of glutamate transporters in the primary cultured astrocytes and in the spinal cord after L5-L6 spinal nerve ligation (SNL), and whether this action of valproate on spinal glutamate transporters prevents spinal glutamate dysregulation and development of hypersensitivity after SNL. In cultured astrocytes, valproate prevented down-regulation of glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST) in a concentration dependent manner. Repeated oral administration of valproate reduced the development of hypersensitivity and prevented the down-regulation of spinal GLT-1 and GLAST expression in rats after SNL, but did not affect mechanical nociception and expression of those transporters in normal rats. Valproate's effects on hypersensitivity and spinal GLT-1 expression in SNL rats were blocked by intrathecal administration of the selective GLT-1 blocker dihydrokainic acid or the GLT-1 selective small interfering RNA (siRNA). Extracellular glutamate concentration in the spinal cord, measured by microdialysis, was increased in animals with SNL or after GLT-1 selective siRNA treatment, and valproate prevented the SNL-induced glutamate increase. These results suggest that valproate reduces the development of chronic pain after nerve injury in part via preventing down-regulation of glutamate transporters, especially GLT-1, to maintain normal extracellular glutamate concentrations in the spinal cord. PMID:24021575

  4. Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats

    PubMed Central

    Long, Ying; Liang, Fang; Gao, Chunjin; Li, Zhuo; Yang, Jing

    2014-01-01

    Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3. PMID:25550916

  5. Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats.

    PubMed

    Long, Ying; Liang, Fang; Gao, Chunjin; Li, Zhuo; Yang, Jing

    2014-01-01

    Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3. PMID:25550916

  6. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    PubMed Central

    Al-Awaida, Wajdy; Akash, Muhanad; Aburubaiha, Zaid; Talib, Wamidh H.; Shehadeh, Hayel

    2014-01-01

    Objective(s): One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. Materials and Methods: Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. Results: Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT. PMID:25729541

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

    PubMed Central

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

    2010-01-01

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

  8. Forelimb anatomy and the discrimination of the predatory behavior of carnivorous mammals: the thylacine as a case study.

    PubMed

    Janis, Christine M; Figueirido, Borja

    2014-12-01

    Carnivorous mammals use their forelimbs in different ways to capture their prey. Most terrestrial carnivores have some cursorial (running) adaptations, but ambush predators retain considerable flexibility in their forelimb movement, important for grappling with their prey. In contrast, predators that rely on pursuit to run down their prey have sacrificed some of this flexibility for locomotor efficiency, in the greater restriction of the forelimb motion to the parasagittal plane. In this article, we measured aspects of the forelimb anatomy (44 linear measurements) in 36 species of carnivorous mammals of known predatory behavior, and used multivariate analyses to investigate how well the forelimb anatomy reflects the predatory mode (ambush, pursuit, or pounce-pursuit). A prime intention of this study was to establish morphological correlates of behavior that could then be applied to fossil mammals: for this purpose, five individuals of the recently extinct thylacine (Thylacinus cynocephalus) were also included as unknowns. We show that the three different types of predators can be distinguished by their morphology, both in analyses where all the forelimb bones are included together, and in the separate analyses of each bone individually. Of particular interest is the ability to distinguish between the two types of more cursorial predators, pursuit and pounce-pursuit, which have previously been considered as primarily size-based categories. Despite a prior consideration of the thylacine as a "pounce-pursuit" or an "ambush" type of predator, the thylacines did not consistently cluster with any type of predatory carnivores in our analyses. Rather, the thylacines appeared to be more generalized in their morphology than any of the extant carnivores. The absence of a large diversity of large carnivorous mammals in Australia, past and present, may explain the thylacine's generalized morphology. PMID:24934132

  9. Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model.

    PubMed

    Deng, Chao; Lian, Jiamei; Pai, Nagesh; Huang, Xu-Feng

    2012-09-01

    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

  10. Nerve-evoked constriction of rat tail veins is potentiated and venous diameter is reduced after chronic spinal cord transection.

    PubMed

    Tripovic, Diana; Al Abed, Amr; Rummery, Nicole M; Johansen, Niloufer J; McLachlan, Elspeth M; Brock, James A

    2011-05-01

    Despite reduced sympathetic activity below the level of a spinal cord injury (SCI), venoconstriction during autonomic dysreflexia increases venous return to the heart. Here, contractions of isometrically mounted tail veins from rats with spinal transection at T4 performed 8?-?10 weeks earlier are compared with those from sham-operated rats. After SCI, lumen diameter was reduced by ?30% and the contractions evoked by electrical stimulation of the perivascular axons were larger than control. This augmentation of neurovascular transmission was not associated with enhanced sensitivity to ?-adrenoceptor agonists or to adenosine-5'-triphosphate (ATP) although contractions to depolarization with K(+) were larger after SCI. The percentage reduction in nerve-evoked contraction after SCI produced by the ?(1)-adrenoceptor antagonist prazosin (10?nM) was unchanged but that by the ?(2)-adrenoceptor antagonist rauwolscine (0.1??M) was reduced. The relative contribution of P2-purinoceptors to nerve-evoked contractions after ?-adrenoceptor blockade, revealed by adding suramin (0.1?mM), was unchanged. The greater depolarization-induced contraction and the reduced contribution of ?(2)-adrenoceptors to nerve-evoked contraction suggest that changes in the venous smooth muscle underlie the potentiation of neurovascular transmission after SCI. Furthermore, the smaller lumen diameter after SCI will increase the pressure that the veins exert on the luminal contents when they are neurally activated. PMID:21222499

  11. Antioxidant Inhibits HMGB1 Expression and Reduces Pancreas Injury in Rats with Severe Acute Pancreatitis

    Microsoft Academic Search

    Zhong Wei Zhang; Qi Yu Zhang; Meng Tao Zhou; Na Xin Liu; Tong Ke Chen; Ye Fan Zhu; Liang Wu

    2010-01-01

    Background  Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis\\u000a therapeutic strategy.\\u000a \\u000a \\u000a \\u000a \\u000a Objective  To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe\\u000a acute pancreatitis and its possible mechanism.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 144 male Sprague–Dawley rats were randomly allocated into a sham operation group

  12. BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in rats.

    PubMed

    Kennett, G A; Ainsworth, K; Trail, B; Blackburn, T P

    1997-02-01

    The 5-HT2B receptor agonist, BW 723C86 (10 and 20 mg/kg s.c.), increased the time spent in feeding behaviour of freely-fed rats in observation cages over 15 min. BW 723C86 (20 and 50 mg/kg s.c. 30 min pre-test) also modestly increased food consumption of freely-fed rats over 1 and 2 hr, but not 4 hr, in their home cages. This action was at least partly mediated centrally, as it was reproduced by i.c.v. infusion of 1 and 10 micrograms in freely-fed rats. The effect is also likely to be 5-HT2B receptor-mediated, as no hyperphagic response to BW 723C86 (20 mg/kg s.c. 30 min pre-test) was observed in freely-fed rats pretreated with the 5-HT2C/2B receptor antagonist SB 206553 (1, 3, 20 or 40 mg/kg p.o. 1 hr pre-test) while the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test), had no effect. Systemic (1, 10 and 20 mg/kg s.c. 30 min pre-test) but not i.c.v. (1-30 micrograms) BW 723C86 also reduced the frequency of grooming bouts of rats in observation cages. BW 723C86 given either s.c. (1-20 mg/kg 30 min pre-test) or i.c.v. (1-30 micrograms) did not cause hypolocomotion, penile erection, oral dyskinesias or hyperthermia, behaviours associated with administration of the 5-HT2C/2B receptor agonist m-chlorophenylpiperazine (mCPP), and are thus likely to involve-5-HT2C receptor activation. PMID:9144661

  13. Reactive oxygen species and cyclooxygenase 2-derived thromboxane A2 reduce angiotensin II type 2 receptor vasorelaxation in diabetic rat resistance arteries.

    PubMed

    Retailleau, Kevin; Belin de Chantemèle, Eric J; Chanoine, Sébastien; Guihot, Anne-Laure; Vessières, Emilie; Toutain, Bertrand; Faure, Sébastien; Bagi, Zsolt; Loufrani, Laurent; Henrion, Daniel

    2010-02-01

    Angiotensin II has a key role in the control of resistance artery tone and local blood flow. Angiotensin II possesses 2 main receptors. Although angiotensin II type 1 receptor is well known and is involved in the vasoconstrictor and growth properties of angiotensin II, the role of the angiotensin II type 2 receptor (AT2R) remains much less understood. Although AT2R stimulation induces vasodilatation in normotensive rats, it induces vasoconstriction in pathological conditions involving oxidative stress and cyclooxygenase 2 expression. Thus, we studied the influence of cyclooxygenase 2 on AT2R-dependent tone in diabetes mellitus. Mesenteric resistance arteries were isolated from Zucker diabetic fatty (ZDF) and lean Zucker rats and studied using in vitro using wire myography. In ZDF rats, AT2R-induced dilation was lower than in lean rats (11% versus 21% dilation). Dilation in ZDF rats returned to the control (lean rats) level after acute superoxide reduction (Tempol and apocynin), cyclooxygenase 2 inhibition (NS398), or thromboxane A(2) synthesis inhibition (furegrelate). Cyclooxygenase 2 expression and superoxide production were significantly increased in ZDF rat arteries compared with arteries of lean rats. After chronic treatment with Tempol, AT2R-dependent dilation was equivalent in ZDF and lean rats. Chronic treatment of ZDF rats with NS398 also restored AT2R-dependent dilation to the control (lean rats) level. Plasma thromboxane B(2) (thromboxane A(2) metabolite), initially high in ZDF rats, was decreased by chronic Tempol and by chronic NS398 to the level found in lean Zucker rats. Thus, in type 2 diabetic rats, superoxide and thromboxane A(2) reduced AT2R-induced dilation. These findings are important to take into consideration when choosing vasoactive drugs for diabetic patients. PMID:20026767

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

    PubMed

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

    2015-05-01

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

  15. Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injury.

    PubMed

    Wagenaar, Gerry T M; Laghmani, El Houari; de Visser, Yvonne P; Sengers, Rozemarijn M A; Steendijk, Paul; Baelde, Hans J; Walther, Frans J

    2013-02-15

    Ambrisentan, an endothelin receptor type A antagonist, may be a novel therapeutic agent in neonatal chronic lung disease (CLD) by blocking the adverse effects of the vasoconstrictor endothelin-1, especially pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We determined the cardiopulmonary effects of ambrisentan treatment (1-20 mg·kg(-1)·day(-1)) in neonatal rats with CLD in 2 models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included survival, lung and heart histopathology, right ventricular function, fibrin deposition, and differential mRNA expression in the lungs. In the early treatment model, we investigated the role of nitric oxide synthase (NOS) inhibition with N(?)-nitro-L-arginine methyl ester (L-NAME; 25 mg·kg(-1)·day(-1)) during ambrisentan treatment. In the early treatment model, ambrisentan improved survival with reduced lung fibrin and collagen III deposition, arterial medial wall thickness, and RVH. These changes were not affected by L-NAME administration. Ambrisentan did not reduce the influx of macrophages and neutrophils or prevent reduced irregular elastin expression. In the late treatment model, ambrisentan diminished PAH, RVH, and right ventricular peak pressure, demonstrating that RVH is reversible in the neonatal period. Alveolarization and vascularization were not affected by ambrisentan. In conclusion, ambrisentan prolongs survival and reduces lung injury, PAH, and RVH via a NOS-independent mechanism but does not affect inflammation and alveolar and vascular development in neonatal rats with CLD. PMID:23292811

  16. Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injury

    PubMed Central

    Laghmani, El Houari; de Visser, Yvonne P.; Sengers, Rozemarijn M. A.; Steendijk, Paul; Baelde, Hans J.; Walther, Frans J.

    2013-01-01

    Ambrisentan, an endothelin receptor type A antagonist, may be a novel therapeutic agent in neonatal chronic lung disease (CLD) by blocking the adverse effects of the vasoconstrictor endothelin-1, especially pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We determined the cardiopulmonary effects of ambrisentan treatment (1–20 mg·kg?1·day?1) in neonatal rats with CLD in 2 models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included survival, lung and heart histopathology, right ventricular function, fibrin deposition, and differential mRNA expression in the lungs. In the early treatment model, we investigated the role of nitric oxide synthase (NOS) inhibition with N?-nitro-l-arginine methyl ester (l-NAME; 25 mg·kg?1·day?1) during ambrisentan treatment. In the early treatment model, ambrisentan improved survival with reduced lung fibrin and collagen III deposition, arterial medial wall thickness, and RVH. These changes were not affected by l-NAME administration. Ambrisentan did not reduce the influx of macrophages and neutrophils or prevent reduced irregular elastin expression. In the late treatment model, ambrisentan diminished PAH, RVH, and right ventricular peak pressure, demonstrating that RVH is reversible in the neonatal period. Alveolarization and vascularization were not affected by ambrisentan. In conclusion, ambrisentan prolongs survival and reduces lung injury, PAH, and RVH via a NOS-independent mechanism but does not affect inflammation and alveolar and vascular development in neonatal rats with CLD. PMID:23292811

  17. 17?-estradiol ameliorates light-induced retinal damage in Sprague-Dawley rats by reducing oxidative stress.

    PubMed

    Wang, Shaolan; Wang, Baoying; Feng, Yan; Mo, Mingshu; Du, Fangying; Li, Hongbo; Yu, Xiaorui

    2015-01-01

    Oxidative stress is considered as a major cause of light-induced retinal neurodegeneration. The protective role of 17?-estradiol (?E2) in neurodegenerative disorders is well known, but its underlying mechanism remains unclear. Here, we utilized a light-induced retinal damage model to explore the mechanism by which ?E2 exerts its neuroprotective effect. Adult male and female ovariectomized (OVX) rats were exposed to 8,000 lx white light for 12 h to induce retinal light damage. Electroretinogram (ERG) assays and hematoxylin and eosin (H&E) staining revealed that exposure to light for 12 h resulted in functional damage to the rat retina, histological changes, and retinal neuron loss. However, intravitreal injection (IVI) of ?E2 significantly rescued this impaired retinal function in both female and male rats. Based on the level of malondialdehyde (MDA) production (a biomarker of oxidative stress), an increase in retinal oxidative stress followed light exposure, and ?E2 administration reduced this light-induced oxidative stress. Quantitative reverse-transcriptase (qRT)-PCR indicated that the messenger RNA (mRNA) levels of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were downregulated in female OVX rats but were upregulated in male rats after light exposure, suggesting a gender difference in the regulation of these antioxidant enzyme genes in response to light. However, ?E2 administration restored or enhanced the SOD and Gpx expression levels following light exposure. Although the catalase (CAT) expression level was insensitive to light stimulation, ?E2 also increased the CAT gene expression level in both female OVX and male rats. Further examination indicated that the antioxidant proteins thioredoxin (Trx) and nuclear factor erythroid 2-related factor 2 (Nrf2) are also involved in ?E2-mediated antioxidation and that the cytoprotective protein heme oxygenase-1 (HO-1) plays a key role in the endogenous defense mechanism against light exposure in a ?E2-independent manner. Taken together, we provide evidence that ?E2 protects against light-induced retinal damage via its antioxidative effect, and its underlying mechanism involves the regulation of the gene expression levels of antioxidant enzymes (SOD, CAT, and Gpx) and proteins (Trx and Nrf2). Our study provides conceptual evidence in support of estrogen replacement therapy for postmenopausal women to reduce the risk of age-related macular degeneration. PMID:25038876

  18. Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats

    PubMed Central

    Kwon, So-Young; Yeom, Jae Hwa

    2014-01-01

    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. PMID:24567814

  19. Three-dimensional skeletal kinematics of the shoulder girdle and forelimb in walking Alligator.

    PubMed

    Baier, David B; Gatesy, Stephen M

    2013-11-01

    Crocodylians occupy a key phylogenetic position for investigations of archosaur locomotor evolution. Compared to the well-studied hindlimb, relatively little is known about the skeletal movements and mechanics of the forelimb. In this study, we employed manual markerless XROMM (X-ray Reconstruction Of Moving Morphology) to measure detailed 3-D kinematics of the shoulder girdle and forelimb bones of American alligators (Alligator mississippiensis) walking on a treadmill. Digital models of the interclavicle, scapulocoracoid, humerus, radius and ulna were created using a 3-D laser scanner. Models were articulated and aligned to simultaneously recorded frames of fluoroscopic and standard light video to reconstruct and measure joint motion. Joint coordinate systems were established for the coracosternal, glenohumeral and elbow joints. Our analysis revealed that the limb joints only account for about half of fore/aft limb excursion; the remaining excursion results from shoulder girdle movements and lateral bending of the vertebral column. Considerable motion of each scapulocoracoid relative to the vertebral column is consistent with coracosternal mobility. The hemisellar design of the glenohumeral joint permits some additional translation, or sliding in the fore-aft plane, but this movement does not have much of an effect on the distal excursion of the bone. PMID:24102540

  20. Three-dimensional Torques and Power of Horse Forelimb Joints at Trot

    E-print Network

    Clayton, H M; Mullineaux, D R

    2011-01-01

    Reasons for Performing Study: Equine gait analysis has focused on 2D analysis in the sagittal plane, while descriptions of 3D kinetics and ground reaction force could provide more information on the Equine gait analysis. Hypothesis or Objectives: The aim of this study was to characterize the 3D torques and powers of the forelimb joints at trotting. Methods: Eight sound horses were used in the study. A full 3D torque and power for elbow, carpus, fetlock, pastern and coffin joints of right forelimb in horses at trot were obtained by calculating the inverse kinetics of simplified link segmental model. Results: Over two third of energy (70%) generated by all joints come from stance phase, and most of energy generated was by elbow joint both in stance (77%) and sway (88%) phases. Energy absorbed by all joints during stance (40%) and sway (60%) phases respectively is not a big difference. During stance phase, all most two third of energy (65%) absorbed was by fetlock joint, while over two third of energy (74%) abso...

  1. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate?

    PubMed Central

    Shahandeh, Mohammad; Roshan, Valiollah Dabidi; Hosseinzadeh, Somayeh; Mahjoub, Soleiman; Sarkisian, Vaginak

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects. PMID:25206718

  2. Immuno-Modulator Metallo-Peptide Reduces Inflammatory State in Obese Zucker Fa/Fa Rats

    PubMed Central

    Gómez-Solís, Antonieta; Reyes-Esparza, Jorge; García-Vázquez, Francisco; Álvarez-Ayala, Elizabeth; Rodríguez-Fragoso, Lourdes

    2014-01-01

    Metabolic syndrome is a prothrombotic and proinflammatory chronic state. In obesity, the adipose tissue secretes various adipokines that take part in a variety of physiological and pathophysiological processes, including immunity and inflammation. Previous studies using a liver damage model treated with the immune-modulator metallo-peptide (IMMP) showed lessening in the degree of inflammation. Therefore, this study was set up to evaluate the anti-inflammatory effect of IMMP in obese Zucker fa/fa rats. We used Zucker-Lepr fa/fa and Zucker-Lean in this protocol. The groups received IMMP 50 ng/kg by i.p., three times per week for 8 weeks. Blood samples were collected by cardiac puncture and the serum was preserved at -80°C until analysis; the liver was excised and preserved in formaldehyde 4%. Analyses were performed to determine cytokine, insulin, glucose, triglyceride and cholesterol levels in serum, and histological analysis was also performed. IMMP treatment of obese rats resulted in decreased levels of proinflammatory cytokines (leptin, lL-6, IL-1betha, INF-gamma) and a chemokine (MCP-1), and increased levels of anti-inflammatory adipokine (adiponectin). In addition, treatment decreased the damage and hepatic steatosis generated in the tissue of obese rats. The IMMP exerted an anti-inflammatory effect in obese rats and therefore may be an effective and safe therapeutic alternative in the treatment of metabolic syndrome. PMID:25324698

  3. Hyperbaric oxygenation pretreatment induces catalase and reduces infarct size in ischemic rat myocardium

    Microsoft Academic Search

    Chan-Hyung Kim; Hong Choi; Yang-Sook Chun; Gi-Tae Kim; Jong-Wan Park; Myung-Suk Kim

    2001-01-01

    Ischemia-reperfusion injury is a major complication occurring in heart stroke, cardiopulmonary bypass surgeries, and heart transplantation. Reactive oxygen species generated during the reperfusion phase overwhelm the scavenging capacities of antioxidant enzymes, and result in oxidative damage to the myocardium. We examined whether hyperbaric oxygenation (HBO) pretreatment induces antioxidant enzymes and protects the heart from subsequent ischemia-reperfusion injury. Rats were intermittently

  4. Central Oxytocin Administration Reduces Stress Induced Corticosterone Release and Anxiety Behavior in Rats

    Microsoft Academic Search

    R. J. WINDLE; N. SHANKS; S. L. LIGHTMAN; C. D. INGRAM

    2009-01-01

    Endocrine responses to noise stress and anxiety-related behaviors were measured in groups of ovariectomized, estradiol-treated female rats given central infusions of oxytocin. Control animals receiving isotonic saline showed a large increase in plasma corticosterone con- centrations in response to 10 min of white noise. This response to noise stress was significantly and dose dependently decreased by oxytocin administered intracerebroventricularly at

  5. 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...

  6. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats

    Microsoft Academic Search

    Mary E Wlodek; Kerryn Westcott; Andrew L Siebel; Julie A Owens; Karen M Moritz

    2008-01-01

    Impaired growth in utero predicts a low nephron number and high blood pressure later in life as does slowed or accelerated growth after a normal birth weight. We measured the effects of early postnatal growth restriction, with or without prenatal growth restriction, on blood pressure and nephron number in male rat offspring. Bilateral uterine artery and vein ligation were performed

  7. Bisphenol-A Impairs Memory and Reduces Dendritic Spine Density in Adult Male Rats

    Microsoft Academic Search

    Tehila Eilam-Stock; Peter Serrano; Maya Frankfurt; Victoria Luine

    2012-01-01

    Exposure to Bisphenol-A (BPA), an endocrine disruptor used in plastics, occurs in the United States on a daily basis. Recent studies suggest exposure during development causes memory deficits later in life; however, the ramifications of exposure in adulthood are unclear. We examined the effects of acute BPA administration (40 ?g\\/kg) on memory and synaptic plasticity in adult male rats. BPA

  8. Hirudin Reduces Tissue Factor Expression and Attenuates Graft Arteriosclerosis in Rat Cardiac Allografts

    Microsoft Academic Search

    Hans Holschermann; Rainer M. Bohle; Heiko Schmidt; Hagen Zeller; Ludger Fink; Ulrich Stahl; Helmut Grimm; Harald Tillmanns; Werner Haberbosch

    Background—Intravascular clotting has been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV). We previously identified the expression of tissue factor (TF), the primary cellular initiator of blood coagulation, within the coronary intima, which was associated with neointimal thickening. In the present study, the effect of recombinant hirudin on CAV was assessed in Lewis to Fisher rat heterotopic cardiac allografts.

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

    SciTech Connect

    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

    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.

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

    Microsoft Academic Search

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

    1995-01-01

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

  11. Reduced pulmonary function is age-dependent in the rat lung in normoxia

    PubMed Central

    2010-01-01

    Background Oxygen transport is optimized at the cellular level, since oxygen serves as the terminal electron acceptor in mitochondrial oxidative phosphorylation and several enzymatic processes require molecular oxygen as substrate. During development and aging, redundant cells and exhausted cells are eliminated, respectively, whereas others can adapt to the stressful environment and survive. Objective The study investigated the molecular mechanisms activated in the lung during normal aging, through the expression of hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), p53, p66Shc, putative cysteine protease (CPP32) and kinaseB-? phosphorylation (pIkB-?). Materials and methods Twelve male Wistar rats divided into two age-groups, each consisting of 6 animals, 3 and 24 months old, were used. The rats were anesthetized with Nembutal (40 mg/kg, ip) and the lungs were excised from each rat and processed for TUNEL and Western blotting analyses. Results The expressions of p53, p66Shc and CPP32 were significantly increased in the old normoxic rat lung specimens, when compared with the young ones. In parallel, expressions of VEGF and pIkB? were increased in old rather than young rats. Conclusions Aging leads to increased expressions of p53, p66Shc and CPP32, suggesting that apoptosis is in progress. At the same time, the lung tries to counteract apoptosis through the production of VEGF and pIkB-? to adapt itself to a stressful situation. The aging lung creates a life-support system in order to counteract the apoptotic process. PMID:21147635

  12. Tempol Treatment Reduces Anxiety-Like Behaviors Induced by Multiple Anxiogenic Drugs in Rats

    PubMed Central

    Patki, Gaurav; Salvi, Ankita; Liu, Hesong; Atrooz, Fatin; Alkadhi, Isam; Kelly, Matthew; Salim, Samina

    2015-01-01

    We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. Using animal models, we also have established that psychological stress induces OS and leads to anxiety-like behaviors. All evidence points towards the causal role of OS in anxiety-like behaviors. To fully ascertain the role of OS in anxiety-like behaviors, it is reasonable to test whether the pro-anxiety effects of anxiogenic drugs caffeine or N-methyl-beta-carboline-3-carboxamide (FG-7142) can be mitigated using agents that minimize OS. In this study, osmotic pumps were either filled with antioxidant tempol or saline. The pumps were attached to the catheter leading to the brain cannula and inserted into the subcutaneous pocket in the back pocket of the rat. Continuous i.c.v. infusion of saline or tempol in the lateral ventricle of the brain (4.3mmol/day) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later all groups were subjected to behavioral assessments. Anxiety-like behavior tests (open-field, light-dark and elevated plus maze) suggested that tempol prevented anxiogenic drug-induced anxiety-like behavior in rats. Furthermore, anxiogenic drug-induced increase in stress examined via plasma corticosterone and increased oxidative stress levels assessed via plasma 8-isoprostane were prevented with tempol treatment. Protein carbonylation assay also suggested preventive effect of tempol in the prefrontal cortex brain region of rats. Antioxidant protein expression and pro-inflammatory cytokine levels indicate compromised antioxidant defense as well as an imbalance of inflammatory response. PMID:25793256

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-04-01

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

  15. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    PubMed

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats. PMID:24579372

  16. Diphenyl diselenide supplementation reduces biochemical alterations associated with oxidative stress in rats fed with fructose and hydrochlorothiazide.

    PubMed

    Ribeiro, Marinei Cristina Pereira; Avila, Daiana Silva; Schiar, Viviane Patrícia Pires; Santos, Danúbia Bonfanti Dos; Meinerz, Daiane F; Duarte, Marta Medeiros Frescura; Monteiro, Roger; Puntel, Robson; de Bem, Andreza Fabro; Hassan, Waseem; de Vargas Barbosa, Nilda Berenice; Rocha, João Batista Teixeira

    2013-08-25

    The study evaluated whether a diet containing diphenyl diselenide (PhSe)2, a synthetic antioxidant, could reduce the biochemical alterations induced by chronic consumption of highly enriched fructose diet and/or hydrochlorothiazide (HCTZ). Rats were fed a control diet (CT) or a high fructose diet (HFD), supplemented with or not HCTZ (4.0g/kg) and/or (PhSe)2 (3ppm) for 18weeks. HFD intake increased significantly plasma glucose, fructosamine, triglycerides and cholesterol levels. (PhSe)2 supplementation significantly reduced triglycerides and cholesterol but could not restore them to control levels. The combination of HFD and HCTZ significantly altered plasma glucose, fructosamine, triglycerides and cholesterol levels which were not restore by (PhSe)2 supplementation. Lipid peroxidation, protein carbonyl formation, vitamin C level and catalase activity decreased after HFD, HCTZ or HFD plus HCTZ ingestion. Remarkably (PhSe)2 supplementation restored the oxidative stress parameters. HCTZ decreased renal superoxide dismutase (SOD) activity, which was restored to control levels by (PhSe)2. Furthermore, the association of HFD and HCTZ decreased plasma potassium levels and aggravated HCTZ-induced hypomagnesemia and hypertriglyceridemia. Here we provided evidence of the involvement of oxidative stress and metabolic disorders in a rat model of HFD associated or not with HTCZ. (PhSe)2 supplementation reduced the oxidative stress and this compound should be considered for the treatment of biochemical disturbances and oxidative stress in other animal models of metabolic disorders. PMID:23707192

  17. Respiratory alkalosis and reduced plasmatic concentration of ionized calcium in rats treated with 1,25 dihydroxycholecalciferol

    Microsoft Academic Search

    M. E. Locatto; M. C. Fernandez; D. A. Caferra; M. C. Gimenez; M. C. Vidal; R. C. Puche

    1984-01-01

    Summary  The daily administration of supraphysiological doses of 1,25 dihydroxycholecalciferol (0.1–2.5 µg\\/d\\/100 g body weight) to\\u000a rats, produced respiratory alkalosis. With the doses of 0.1–0.2 µg\\/d\\/100 g and feeding a diet with 0.7% of calcium, calcemias\\u000a did not exceed 2.75 mM, and significantly reduced plasma ionized calcium levels were measured. The latter phenomenon was found\\u000a associated with increased urinary excretion of

  18. Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats

    PubMed Central

    Novaes, Rômulo D; Gonçalves, Reggiani V; Cupertino, Marli C; Marques, Daiane C S; Rosa, Damiana D; Peluzio, Maria do Carmo G; Neves, Clóvis A; Leite, João Paulo V

    2012-01-01

    Summary This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage. PMID:22429505

  19. Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment.

    PubMed

    Hernández-Plata, Everardo; Quiroz-Compeán, Fátima; Ramírez-Garcia, Gonzalo; Barrientos, Eunice Yáñez; Rodríguez-Morales, Nadia M; Flores, Alberto; Wrobel, Katarzina; Wrobel, Kazimierz; Méndez, Isabel; Díaz-Muñoz, Mauricio; Robles, Juvencio; Martínez-Alfaro, Minerva

    2015-03-01

    Melatonin, a hormone known for its effects on free radical scavenging and antioxidant activity, can reduce lead toxicity in vivo and in vitro.We examined the effects of melatonin on lead bio-distribution. Rats were intraperitoneally injected with lead acetate (10, 15 or 20mg/kg/day) with or without melatonin (10mg/kg/day) daily for 10 days. In rats intoxicated with the highest lead doses, those treated with melatonin had lower lead levels in blood and higher levels in urine and feces than those treated with lead alone, suggesting that melatonin increases lead excretion. To explore the mechanism underlying this effect, we first assessed whether lead/melatonin complexes were formed directly. Electronic density functional (DFT) calculations showed that a lead/melatonin complex is energetically feasible; however, UV spectroscopy and NMR analysis showed no evidence of such complexes. Next, we examined the liver mRNA levels of metallothioneins (MT) 1 and 2. Melatonin cotreatment increased the MT2 mRNA expression in the liver of rats that received the highest doses of lead. The potential effects of MTs on the tissue distribution and excretion of lead are not well understood. This is the first report to suggest that melatonin directly affects lead levels in organisms exposed to subacute lead intoxication. PMID:25601058

  20. Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney.

    PubMed

    Hirose, Yasuhiko; Yasui, Takahiro; Taguchi, Kazumi; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Okada, Atsushi; Kubota, Yasue; Kawai, Noriyasu; Itoh, Yasunori; Tozawa, Keiichi; Sasaki, Shoichi; Kohri, Kenjiro

    2013-08-01

    Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-?-D-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones. PMID:23754513

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

    PubMed Central

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

    2014-01-01

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

  2. Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats.

    PubMed

    El-Ghoneimi, A; Cursio, R; Schmid-Alliana, A; Tovey, M; Lasfar, A; Michiels, J-F; Rossi, B; Gugenheim, J

    2007-01-01

    Pentoxifylline (PTX) has been shown to protect the liver against normothermic ischemia-reperfusion (I-R) injury. The aims of this study were to investigate the action of PTX on tumor necrosis factor alpha (TNFalpha) gene transcription following normothermic liver I-R as well as to evaluate the resulting effects on liver function and survival. A segmental normothermic liver ischemia was induced for 90 minutes. Rats were divided into three groups: group 1, control, Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 minutes before induction of ischemia and 30 minutes before reperfusion. The nonischemic liver lobes were resected at the end of ischemia. Survival rates were compared and serum activities of TNFalpha, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Liver histology was assessed 6 hours after reperfusion. Liver TNFalpha mRNA was assessed by polymerase chain reaction amplification at different times after reperfusion. PTX treatment significantly decreased serum activities of TNFalpha and inhibited liver expression of TNFalpha mRNA. The extent of liver necrosis and serum levels of liver enzymes were significantly decreased by PTX treatment, resulting in a significant increase in 7-day survival compared with nontreated control rats. In conclusion, PTX inhibits liver TNFalpha gene transcription, decreases serum TNFalpha levels, and reduces liver injury following normothermic I-R. PMID:17692605

  3. Topically administered timolol and dorzolamide reduce intraocular pressure and protect retinal ganglion cells in a rat experimental glaucoma model

    PubMed Central

    Seki, M; Tanaka, T; Matsuda, H; Togano, T; Hashimoto, K; Ueda, J; Fukuchi, T; Abe, H

    2005-01-01

    Aims: This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat. Methods: Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears (vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number. Results: Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p<0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p<0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r?=??0.908, p<0.005), but not in other groups (p>0.05). Conclusions: Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP. PMID:15774933

  4. [Effects of diazepam and baclofen on the anemic decerebrate rigidity in rats (author's transl)].

    PubMed

    Fukuda, H

    1979-09-01

    Effects of diazepam and baclofen on the anemic decerebrate rigidity in rats were studied by using the drugs that modify GABAergic mechanisms of deplete catecholamine. Rigid forelimb tension in anemic decerebrate rats took the form of tonically sustained tension (tonic component), while the phasic tension (phasic component) was induced by mechanical stimulation of hindlimbs. Diazepam exerted a marked dose-dependent inhibition of the phasic component, whereas baclofen produced a similar effect on both tonic and phasic components. In rats pretreated with semicarbazide, the inhibitory effect of diazepam on phasic component was reduced, and the effect of semicarbazide was antagonized by pyridoxine. The effect of diazepam was slightly enhanced by pretreatment with aminooxyacetic acid, and antagonized by picrotoxin. In contrast to diazepam, the depressant actions of baclofen on both components were not affected by semicarbazide, aminooxyacetic acid or picrotoxin. Catecholamine depletion produced by alpha-methyltyrosine or disulfiram significantly reduced the effect of baclofen on the phasic component. It thus appears that GABA is involved in the effect of diazepam on the phasic component, and noradrenaline is involved in the same effect of baclofen in anemic decerebrate rats. PMID:540883

  5. Chronic Di-n-butyl Phthalate Exposure in Rats Reduces Fertility and Alters Ovarian Function During Pregnancy in Female Long Evans Hooded Rats

    Microsoft Academic Search

    L. E. Gray; John Laskey; Joseph Ostby

    2006-01-01

    Testis function in fetal and peripubertal male rats is disrupted by subchronic exposure to phthalate esters (PEs). In contrast to the male rat, it is generally held that reproduction in female rats is much less sensitive to phthalate-induced disruption. However, the current study demonstrates that oral administration of dibutyl phthalate (DBP) to female Long Evans (LE) hooded rats from weaning,

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

    PubMed

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

    1995-01-01

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

  7. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala.

    PubMed

    Hari Dass, Shantala Arundhati; Vyas, Ajai

    2014-12-01

    Male rats (Rattus novergicus) infected with protozoan Toxoplasma gondii relinquish their innate aversion to the cat odours. This behavioural change is postulated to increase transmission of the parasite to its definitive felid hosts. Here, we show that the Toxoplasma gondii infection institutes an epigenetic change in the DNA methylation of the arginine vasopressin promoter in the medial amygdala of male rats. Infected animals exhibit hypomethylation of arginine vasopressin promoter, leading to greater expression of this nonapeptide. The infection also results in the greater activation of the vasopressinergic neurons after exposure to the cat odour. Furthermore, we show that loss of fear in the infected animals can be rescued by the systemic hypermethylation and recapitulated by directed hypomethylation in the medial amygdala. These results demonstrate an epigenetic proximate mechanism underlying the extended phenotype in the Rattus novergicus-Toxoplasma gondii association. PMID:25142402

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

    Microsoft Academic Search

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

    1998-01-01

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

  9. Benzodiazepines reduce stress-augmented increase in rat urine monoamine oxidase inhibitor

    Microsoft Academic Search

    Vivette Glover; S. K. Bhattacharya; M. Sandler; Sandra E. File

    1981-01-01

    Normal human urine inhibits monoamine oxidase (MAO)1. This inhibitory activity, which is also present in rat urine, cannot be accounted for by a large range of known urinary constituents, including certain monoamines or their metabolites, but is caused by an unidentified low-molecular-weight compound(s). Endogenous MAO inhibitors may be important as physiological regulators; there have been reports of a decrease in

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

    PubMed Central

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

    2011-01-01

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

  11. D-ribose attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.

    PubMed

    Sato, Hitoaki; Ueki, Masaaki; Asaga, Takehiko; Chujo, Kousuke; Maekawa, Nobuhiro

    2009-05-01

    The ischemia/reperfusion (I/R) represents a common pathological mechanism that causes renal injuries. A monosaccharide D-allose has been shown to inhibit neutrophil activation, which is involved in the I/R-induced organ injuries. We therefore examined the role of D-ribose in the I/R-induced renal injury using a rat model. D-ribose, a monosaccharide found in all living cells, serves as a key component of adenosine-5'-triphosphate and nicotinamide adenine dinucleotide. Male Wistar rats were divided into the sham, control and D-ribose groups. In the control and D-ribose groups, rats were subjected to 45 min of left renal ischemia, followed by 24 h of reperfusion, while the I/R procedure was not performed in the sham group. Rats were intravenously administered D-ribose (sham group and D-ribose group, 400 mg/kg) or saline (control group) 30 min before ischemia. Blood urea nitrogen (BUN), serum creatinine and urinary N-acetyl beta-D-glucosaminidase (NAG) were measured as indicators of glomerular function and proximal tubular function. We also measured cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase concentrations to assess neutrophil activation and infiltration, respectively. The tissue sections were scored to evaluate the tubular injury. In the control group, BUN, creatinine, NAG, CINC-1, myeloperoxidase, histological severity score, and number of infiltrating neutrophils were increased following I/R insult, as compared with the sham group. Such increases in biochemical markers, severity score, and infiltrating neutrophils were significantly inhibited in the D-ribose group. Thus, D-ribose ameliorates the I/R-induced renal injury probably by inhibiting neutrophil activation, and may be useful in attenuating the renal injury associated with renal ischemia. PMID:19398871

  12. Leptin Inhibits Insulin Secretion and Reduces Insulin mRNA Levels in Rat Isolated Pancreatic Islets

    Microsoft Academic Search

    Anna L. Pallett; Nicholas M. Morton; Michael A. Cawthorne; Valur Emilsson

    1997-01-01

    The ob gene product leptin over the concentration range 0.1–100nM demonstrated a U-shaped dose–response inhibition of glucose-stimulated insulin secretion by rat pancreatic islets. Thus, leptin (1 and 10nM) produced a significant inhibition whereas 100nM was ineffective. The inhibitory effect of leptin was glucose dependent, had a rapid onset and was readily reversed upon removal of leptin. Sub-chronic exposure of islets

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

    Microsoft Academic Search

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

    2008-01-01

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

  14. Crizotinib reduces the rate of dark adaptation in the rat retina independent of ALK inhibition.

    PubMed

    Liu, Chang-Ning; Mathialagan, Nagappan; Lappin, Patrick; Fortner, Jay; Somps, Chris; Seitis, Gary; Johnson, Theodore R; Hu, Wenyue; Matsumoto, Diane

    2015-01-01

    Crizotinib (Xalkori) is a tyrosine kinase inhibitor of both anaplastic lymphoma kinase (ALK) and mesenchymal-epithelial transition factor (c-Met). Though not predicted from standard nonclinical toxicological evaluation, visual disturbance became a frequently observed adverse event in humans. To understand the possible mechanism of this vision effect, an in vivo electroretinogram (ERG) study was conducted to assess retinal functional changes following oral administration of crizotinib. Immunohistochemical (IHC) staining of ALK and c-Met in the neural retinas of human, non-human primate, dog, rat, and mouse was used to aid in the animal model selection. ALK IHC staining was identified predominantly in the ganglion cell and inner nuclear layers of most species evaluated, in the inner plexiform layer in human and rodent, and in the nerve fiber layer in human and rat only. There was no apparent staining of any layer of the neural retina for c-Met in any of the species evaluated. ERG measurements identified a significant reduction in b-wave amplitude during the initial phase of dark adaptation in the crizotinib-treated rats. ERGs were also taken following oral administration of PF-06463922 (an ALK-selective inhibitor), for an understanding of potential kinase involvement. ERG effects were not observed in PF-06463922-treated animals when comparable exposures in the vitreous humor were achieved. Collectively, our results suggest that the ERG b-wave amplitude decreases during dark adaption following crizotinib administration may be related to signaling changes within the retina in rats, likely independent of ALK inhibition. PMID:25326243

  15. Diabetic rats show reduced cardiac–somatic reflex evoked by intrapericardial capsaicin

    Microsoft Academic Search

    Xiao-Hua Liu; Chao Qin; Jian-Qing Du; Yan Xu; Na Sun; Jing-Shi Tang; Qiang Li; Robert D. Foreman

    2011-01-01

    Painless myocardial infarction is a serious complication of diabetes. The present study examined whether cardiac nociception was altered in the streptozotocin-induced diabetic rat model by assessing intrapericardial capsaicin-evoked electromyography (EMG) responses in the spinotrapezius muscle. Somatic sensitivities to mechanical and thermal stimulation of the skin were also determined. Intrapericardial administration of capsaicin evoked a concentration-dependent EMG response, which was reproducible

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

    Microsoft Academic Search

    T. Hirota; A. Minakawa; M. Muraguchi

    1990-01-01

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

  17. Memantine reduces functional and morphological consequences induced by global ischemia in rats

    Microsoft Academic Search

    F. Block; M. Schwarz

    1996-01-01

    In this study the effect of memantine, an antagonist at the N-methyl-d-aspartate receptor, on spatial learning deficit and on neuronal damage following transient: cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Memantine was administered 20 min before induction of ischemia at a dose of 10 or 20 mg\\/kg. One week after surgery

  18. Low doses of naltrexone reduce palatability and consumption of ethanol in outbred rats

    Microsoft Academic Search

    Daniel L. Coonfield; Katherine G. Hill; Helen J. Kaczmarek; Frank M. Ferraro; Stephen W. Kiefer

    2002-01-01

    The opioid antagonist naltrexone, at doses of 1 and 3 mg\\/kg, has been shown to decrease the palatability and consumption of 10% ethanol in rats. However, a dose of 0.5 mg\\/kg of naltrexone has produced equivocal results. The purpose of the present study was to clarify the effects of low doses of naltrexone (0.0 [control], 0.25, 0.50, 0.75, and 1.0

  19. Montelukast reduces sepsis-induced lung and renal injury in rats.

    PubMed

    Khodir, Ahmed E; Ghoneim, Hamdy A; Rahim, Mona Abdel; Suddek, Ghada M

    2014-10-01

    This study was undertaken to examine the effects of montelukast (MNT) on lung and kidney injury in lipopolysaccharide (LPS) induced systemic inflammatory response. Rats were randomized into 5 groups (n = 8 rats/group): (i) Control; (ii) LPS treated (10 mg/kg body mass, by intraperitoneal (i.p.) injection); (iii) LPS + MNT (10 mg/kg, per oral (p.o.)); (iv) LPS + MNT (20 mg/kg, p.o); (v) LPS + dexamethasone (DEX; 1 mg/kg, i.p.). Twenty-four hours after sepsis was induced, the lung or kidney:body mass ratio and percent survival of rats were determined. Creatinine, blood urea nitrogen (BUN), albumin, total protein, and LDH activity were measured. Lung and kidney samples were taken for histological assessment and for determination of their malondialdehyde (MDA) and glutathione (GSH) contents. The expression of tumour necrosis factor ? (TNF-?) in tissue was evaluated immunohistochemically. LPS significantly increased the organ:body mass ratio, serum creatinine, BUN, and LDH, and decreased serum albumin and total protein levels. MDA levels increased in lung and kidney tissues after treatment with LPS, and there was a concomitant reduction in GSH levels. Immunohistochemical staining of lung and kidney specimens from LPS-treated rats revealed high expression levels of TNF-?. MNT suppresses the release of inflammatory and oxidative stress markers. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. These results demonstrate that MNT could have lung and renoprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and (or) anti-inflammatory properties. PMID:25243774

  20. Multiple presentations reduce the behavioral impact of protected predator exposure in rats.

    PubMed

    Genovese, Raymond F; Johnson, Christina C; Tobin, Christine A; Gauchan, Sangeeta

    2014-10-01

    Exposure of rats to a predator species, such as a cat, or stimuli associated with a predator species has been used to model the effects of traumatic stress. We further investigated this procedure to determine if the behavioral effects from such exposure could be increased by multiple exposures. In rats (n=8 for each treatment group), we evaluated single (1×) and multiple (1×/day for 3 consecutive days [3×] and 2×/day for 3 consecutive days [6×]) exposures using cats and soiled cat litter. All exposures were 15min in duration and the rats were directly exposed to the cats but in a protected fashion that did not allow the predator to physically injure the rat. Sham exposures were conducted using similar conditions without the presence of the predator or litter. The effects of the exposures were evaluated using an elevated plus maze (EPM). Sessions on the EPM were conducted before the exposures and at various times after the exposure. Difference scores (post-pre) were calculated for dependent measures from the EPM, and statistical analyses compared the slopes and intercept values derived from regression functions from these scores over the post-exposure sessions. During the first 30 days after exposure, a significant reduction in activity on the EPM was observed for the 1× treatment and a smaller reduction was observed for the 3× treatment, but no reduction was observed for the 6× and sham control treatments. Thus, increasing the number of exposures did not increase the magnitude of the effect but, instead, resulted in a decrease. These results show that adaptation to the effects of the predator exposure occurred with repeated sessions. PMID:25280946

  1. Prenatal ethanol exposure reduces phosphoinositide hydrolysis stimulated by quisqualate in rat cerebellar granule cell cultures

    Microsoft Academic Search

    Philip G. Rhodes; Zhengwei Cai; Nannan Zhu

    1994-01-01

    Prenatal ethanol exposure-induced alteration in poly-phosphoinositide (PPI) hydrolysis stimulated by excitatory amino acids\\u000a (EAA) was studied in rat cerebellar granule cells previously labeled with [3H]myoinositol. The prenatal exposure to ethanol was achieved via maternal consumption of a Sustacal (chocolate flavored) liquid\\u000a diet containing either 5% ethanol (w\\/v, 35% of calories) or isocaloric sucrose (pair-fed) substituted for ethanol from gestation\\u000a d

  2. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Ryan, J L

    1984-12-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V). PMID:6505141

  3. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPAR? as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNF? mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-?B mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNF?-mediated inflammation.

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

    PubMed Central

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

    2013-01-01

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

  5. Intrathecal l-arginine reduces the antinociception of sevoflurane in formalin-induced pain in rats.

    PubMed

    Chen, Jian-Qing; Zeng, Yin-Ming; Dai, Ti-Jun; Tang, Qi-Feng

    2015-03-17

    The purpose of this study was to investigate the contribution of spinal nitric oxide (NO) to the antinociceptive effects of emulsified sevoflurane in rats. Formalin tests were used to assess the nociceptive response. Immunohistochemistry was performed to determine the effects of emulsified sevoflurane on formalin-induced changes of Fos-like immunoreactive (Fos-LI)-positive neurons in the spinal cord. We found that emulsified sevoflurane administered intraperitoneally at a dosage of 2.5ml/kg did not impair motor performance in rats, but it significantly decreased the formalin-induced paw licking time. Furthermore, Fos-LI-positive neurons were mainly found in the ipsilateral dorsal horn after the injection of formalin. The administration of emulsified sevoflurane significantly decreased Fos-LI-labeled neurons. Finally, intrathecal l-arginine alone did not affect the basal pain threshold, but it significantly decreased the antinociceptive response of emulsified sevoflurane against formalin injection and the suppressive effects of sevoflurane on formalin-induced Fos protein expression (P<0.05). These data suggest that spinal cord NO is involved in the antinociception of sevoflurane in rats. PMID:25660619

  6. Sphingosine kinase 1 knockdown reduces insulin synthesis and secretion in a rat insulinoma cell line.

    PubMed

    Hasan, N M; Longacre, M J; Stoker, S W; Kendrick, M A; Druckenbrod, N R; Laychock, S G; Mastrandrea, L D; MacDonald, M J

    2012-02-01

    To evaluate the role of sphingosine kinase 1 (SphK1) in insulin secretion, we used stable transfection to knock down the expression of the Sphk1 gene in the rat insulinoma INS-1 832/13 cell line. Cell lines with lowered Sphk1 mRNA expression and SphK1 enzyme activity (SK11 and SK14) exhibited lowered glucose- and 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) plus glutamine-stimulated insulin release and low insulin content associated with decreases in the mRNA of the insulin 1 gene. Overexpression of the rat or human Sphk1 cDNA restored insulin secretion and total insulin content in the SK11 cell line, but not in the SK14 cell line. The Sphk1 cDNA-transfected SK14 cell line expressed significantly less SphK1 activity than the Sphk1 cDNA-transfected SK11 cells suggesting that the shRNA targeting SK14 was more effective in silencing the exogenous rat Sphk1 mRNA. The results indicate that SphK1 activity is important for insulin synthesis and secretion. PMID:22155656

  7. Melatonin reduces inflammation and recovers endogenous ghrelin in acute necrotizing pancreatitis in rats.

    PubMed

    Liang, Zhi-Hai; Qin, Meng-Bin; Tang, Guo-Du; Yang, Hui-Ying; Su, Juan; Huang, Jie-An

    2014-06-01

    The present study aimed to evaluate the therapeutic effects of melatonin on either ghrelin secretion or gastric mucosal injury in acute necrotizing pancreatitis (ANP). ANP was induced in rats by L-arginine. Prior to L-arginine injection, the rats were pre-treated with melatonin for 30 min. Following the last injection, the animals were sacrificed at different time-points. The levels of ghrelin and melatonin in the serum and gastric tissue were detected by ELISA. Levels of tumor necrosis factor (TNF)-?, interleukin (IL)-6 and malondialdehyde (MDA) as well as total superoxide dismutase (T-SOD) activities in gastric tissue were measured. In rats with ANP, acute gastric injury was observed, and the levels of MDA, SOD, TNF-? and IL-6 were significantly increased. The melatonin levels in serum or gastric tissue peaked at 6 h and returned to normal levels at 12 h after melatonin was administered. However, ghrelin remained at low levels during the first 12 h, but it recovered at 24 h and continued increasing, while the levels of oxidative stress damage and activity of inflammatory factors were decreased. The protective effects of melatonin on acute gastric injury during the early stages of ANP may be mediated through anti-oxidative and anti-inflammatory activities, while at advanced stages of ANP, it may be mediated through the recovered endogenous ghrelin. PMID:24718676

  8. Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart.

    PubMed

    Sattari, Saeed; Dryden, William F; Eliot, Lise A; Jamali, Fakhreddin

    2003-07-01

    1. Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. 2. 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. 3. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. 4. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. 5. 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. 6. Maximum binding of (3)H-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. 7. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml(-1) of rat tissue necrosis factor-alpha did not influence the binding indices to the calcium channels. 8. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels. PMID:12839868

  9. Neither Milk Production, Milk Transfer Nor Pup Growth Hormone Account for Reduced Body Weights of Rat Pups Reared In Hypergravity

    NASA Technical Reports Server (NTRS)

    Bear, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Studies spanning the gravity continuum from 0 to 2-g are revealing new insights into how mammalian reproduction and development may proceed in the microgravity of space. Rat pups reared from either conception or midgestation in hypergravity (hg) weigh 6-15% less than 1-g controls. In the present study we analyzed maternal and pup factors that may account for reduced body weight of hg reared pups. Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g, 1.75-g or 2.0-g. Prolaction (Prl) and oxytocin (OT) were measured in hg-exposed dams during either pregnancy (G20) or lactation (Postnatal day [P] 10). Gravity related differences in Prl were not observed whereas OT was depressed during lactation in hg dams relative to controls (p less than 0.05). Milk transfer measured during a discrete suckling episode was actually increased in hg-reared litters and comparable numbers of milk-letdowns were observed in the two conditions. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on growth hormone (GH) and insulin-like growth factors (IGFs). Plasma GH measured in P10 pups using enzyme immunoassay (EIA) was significantly elevated in hg pups relative to 1-g controls (mean +/- sd., ng/ml: 2.0-g, 10.6 [3.0], 1.5-g 8.9 [4.0], 1.0-g, 7.95 [3.1]). Together, these findings suggest that neither milk production, milk transfer nor pup GH play significant roles in reduced body weights of hg-reared pups. Studies underway are focused on insulin-like growth factors.

  10. Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats.

    PubMed

    Andalib, S; Shayanfar, A; Khorrami, A; Maleki-Dijazi, N; Garjani, A

    2014-05-01

    The present study was aimed to study the effects of different doses of atorvastatin on Co Q10 content in the myocardium tissue in rats. A subcutaneous injection of isoproterenol (5?mg/kg/day) for 10 days was used for the induction of heart failure. Rats were randomly assigned to control, treatment with atorvastatin (5, 10, 20?mg/kg/day) and treatment with atorvastatin plus coenzyme Q10 (10?mg/kg/day). Coenzyme Q10 content of myocardium was measured using HPLC method with UV detector after hemodynamic parameters measurements. The malondialdehyde (MDA) content of the myocardium was evaluated in order to determine coenzyme Q10 antioxidative effect. A high dose of atorvastatin (20?mg/kg/day) was significantly reduced the myocardium content of coenzyme Q10 as compared with isoproterenol treated group (p<0.001). Compared with atorvastatin alone treated animals, co-administration of coenzyme Q10 with atorvastatin was improved the level of coenzyme Q10 in the myocardium (p<0.05, p<0.001). Increasing the dose of atorvastatin also led to increase in MDA content of the myocardium (p<0.01). Serum lipid profile showed no changes in atorvastatin treated groups. The results of this study demonstrate that high doses of atorvastatin reduce coenzyme Q10 content of the myocardium and increase lipid peroxidation in myocardium which is reversed by coenzyme Q10 co-administration. PMID:24154934

  11. Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats

    PubMed Central

    Hua, Jie; He, Zhi-Gang; Qian, Dao-Hai; Lin, Sheng-Ping; Gong, Jian; Meng, Hong-Bo; Yang, Ting-Song; Sun, Wei; Xu, Bin; Zhou, Bo; Song, Zhen-Shun

    2014-01-01

    Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-?, IFN-?, IL-1?, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene-modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP. PMID:25120736

  12. Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats.

    PubMed

    Hua, Jie; He, Zhi-Gang; Qian, Dao-Hai; Lin, Sheng-Ping; Gong, Jian; Meng, Hong-Bo; Yang, Ting-Song; Sun, Wei; Xu, Bin; Zhou, Bo; Song, Zhen-Shun

    2014-01-01

    Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-?, IFN-?, IL-1?, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene-modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP. PMID:25120736

  13. Dietary supplementation with (-)-epigallocatechin-3-gallate reduces inflammatory response in adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats.

    PubMed

    Uchiyama, Yumiko; Suzuki, Takuji; Mochizuki, Kazuki; Goda, Toshinao

    2013-11-27

    (-)-Epigallocatechin gallate (EGCG), a major catechin in green tea, is an antioxidant associated with the reduction of oxidative stress in vitro. However, the mechanisms underlying the effects of EGCG on adipose tissue-related metabolic disturbances in vivo are not understood. This study examined whether dietary supplementation of EGCG reduces the oxidative stress-associated inflammatory response in the mesenteric adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats. GK rats were fed a normal diet or diet containing 0.1, 0.2, or 0.5% EGCG (w/w) for 25 weeks. The mRNA levels of IL-1? were significantly reduced in GK rats given 0.1% EGCG (0.059 ± 0.008; means ± SEM in arbitrary unit) compared with those in GK rats given a control diet (0.135 ± 0.011), but not in those given 0.2% EGCG (0.123 ± 0.012) or 0.5% EGCG (0.112 ± 0.019). The mRNA and protein level of other genes for inflammatory responses such as IL-18, TNF-?, MCP-1, CD11s, CD18, and resistin were also significantly reduced in rats given 0.1% EGCG, but not in those given ? 0.2% EGCG. This suggests that supplementation with EGCG at relatively low concentrations (0.1%) in GK rats reduces expression of genes and proteins involved in inflammation in adipose tissue. PMID:24206061

  14. Pretreatment of liver grafts in vivo by ?-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat

    PubMed Central

    Hori, Tomohide; Gardner, Lindsay B.; Hata, Toshiyuki; Chen, Feng; Baine, Ann-Marie T.; Uemoto, Shinji; Nguyen, Justin H.

    2014-01-01

    Summary Background: Gamma-aminobutyric acid (GABA) is found throughout the body. The regulation of GABA receptor (GABAR) reduces oxidative stress (OS). Ischemia/reperfusion injury after orthotopic liver transplantation (OLT) causes OS-induced graft damage. The effects of GABAR regulation in donors in vivo were investigated. Material/Methods: Donor rats received saline, a GABAR agonist or GABAR antagonist 4 h before surgery. Recipient rats were divided into four groups according to the donor treatments: laparotomy, OLT with saline, OLT with GABAR agonist and OLT with GABAR antagonist. Histopathological, biochemical and immunohistological examinations were performed at 6, 12 and 24 h after OLT. Protein assays were performed at 6 h after OLT. The 4-hydroxynonenal (4-HNE), ataxia-telangiectasia mutated kinase (ATM), phosphorylated histone H2AX (?H2AX), phosphatidylinositol-3 kinase (PI3K), Akt and superoxide dismutase (SOD) were assessed by western blot analysis. Results: In the univariate analysis, histopathological and biochemical profiles verified that the GABAR agonist reduced graft damage. Immunohistology revealed that the GABAR agonist prevented the induction of apoptosis. Measurement of 4-4-HNE levels confirmed OS-induced damage after OLT, and the GABAR agonist improved this damage. In the ?H2AX, PI3K, Akt and antioxidant enzymes (SODs), ATM and H2AX were greatly increased after OLT, and were reduced by the GABAR agonist. In the multivariate analyses between multiple groups, histopathological assessment, aspartate aminotransferase level, immunohistological examinations for apoptotic induction and ?H2AX showed statistical differences. Conclusions: A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway. PMID:23792534

  15. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues.

    PubMed

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

  16. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

    PubMed Central

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

  17. Glutamine reduces bacterial translocation after small bowel transplantation in cyclosporine-treated rats.

    PubMed

    Zhang, W; Frankel, W L; Bain, A; Choi, D; Klurfeld, D M; Rombeau, J L

    1995-02-01

    Bacterial translocation (BT) of enteric organisms is a major cause of sepsis in patients undergoing small bowel transplantation (SBT). Cyclosporine (CsA) may be toxic to intestinal epithelium and increase the risk of BT. Glutamine (Gln) is the preferred enterocyte fuel and maintains graft epithelial integrity in experimental SBT. This study determined the effects of CsA on mucosal structure and function of transplanted intestinal isograft and examined whether Gln-enriched diet reversed CsA-induced intestinal toxicity. Thirty-three adult Lewis rats underwent resection of the distal 60% of small bowel and received an orthotopic jejunal isograft. Rats received either elemental diet with 2% Gln or the same diet with balanced nonessential amino acids (non-Gln) by gastrostomy for 10 days. CsA (15 mg/kg, im) or olive oil was injected daily. Rats were assigned to four groups: non-Gln with vehicle, non-Gln with CsA, Gln with vehicle, and Gln with CsA. Mucosal villous height, surface area, crypt depth, 14C glucose absorption, BT to mesenteric lymph nodes (MLN), and body weight change were evaluated. The non-Gln with CsA group had the highest incidence of BT (P < 0.001). Gln groups had significantly decreased BT (P < 0.01) and increased crypt depth and villous surface area (P < 0.01) when compared to non-Gln groups. Body weight significantly decreased in CsA groups when compared to non-CsA groups (P < 0.01). These results indicate at CsA significantly decreased body weight and increased BT without decreasing mucosal structure and glucose absorption of intestinal isografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7861767

  18. Activation of PPAR gamma receptors reduces levodopa-induced dyskinesias in 6-OHDA-lesioned rats.

    PubMed

    Martinez, A A; Morgese, M G; Pisanu, A; Macheda, T; Paquette, M A; Seillier, A; Cassano, T; Carta, A R; Giuffrida, A

    2015-02-01

    Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPAR? subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPAR? may represent a new pharmacological target for the treatment of LID. PMID:25486547

  19. Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats

    PubMed Central

    Vidal, R; Valdizan, EM; Vilaró, MT; Pazos, A; Castro, E

    2010-01-01

    BACKGROUND AND PURPOSE The 5-HT4 receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT4 receptor-mediated signalling events. EXPERIMENTAL APPROACH The effects of 21 days treatment (p.o.) with high (40 mg·kg?1) and low (10 mg·kg?1) doses of venlafaxine, were evaluated at different levels of 5-HT4 receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg?1, 21 days) was also evaluated on 5-HT4 receptor density. KEY RESULTS Treatment with a high dose (40 mg·kg?1) of venlafaxine did not alter 5-HT4 mRNA expression, but decreased the density of 5-HT4 receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg?1) while it was attenuated in rats treated with 40 mg·kg?1 of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT4 receptor density. CONCLUSIONS AND IMPLICATIONS Our data indicate a functional desensitization of 5-HT4 receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake. PMID:20880406

  20. Role of Reactive Oxygen Species in Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats

    PubMed Central

    Sedeek, Mona; Gilbert, Jeffrey S.; LaMarca, Babbette B.; Sholook, Myssara; Chandler, Derrick L.; Wang, Yuping; Granger, Joey P.

    2009-01-01

    BACKGROUND Although recent studies indicate preeclampsia (PE) is associated with increased oxidative stress, the role of reactive oxygen species in the hypertension associated with PE remains unclear. We sought to test the hypothesis that placental ischemia increases oxidative stress which in turn, contributes to hypertension. METHODS Reduction in uterine perfusion pressure (RUPP) was induced by placing silver clips on the abdominal aorta and the ovarian arteries on day 14 of pregnancy. On day 20 of pregnancy, mean arterial pressure (MAP) was measured and oxidative stress was assessed in renal and placental tissues whereas systemic administration of tempol, a superoxide dismutase (SOD) mimetic, was used to evaluate the contribution of reactive oxygen species on RUPP-induced hypertension. RESULTS MAP (120 ± 2 mm Hg vs.106 ± 3 mm Hg), placental levels of 8-isoprostane (1.9 ± 0.4 ng/g tissue vs. 0.8 ± 0.1 ng/g tissue), and malondialdehyde (MDA) (6.9 ± 0.6 ?mol/g tissue vs. 3.9 ± 0.4 ?mol/g tissue) were increased, whereas renal cortical SOD activity was decreased in RUPP rats (1.2 ± 0.1 units/mg protein vs. 1.6 ± 0.1 units/ mg protein) at day 20 of gestation (20 dG) compared to controls. Chronic treatment with tempol attenuated the hypertension (RUPP + tempol 112 ± 2 mm Hg vs. RUPP, 120 ± 2 mm Hg) associated with RUPP, whereas tempol had no effect on MAP (NP, 106 ± 3 vs. NP + tempol, 108 ± 2) in control rats. CONCLUSION The results of this study indicate that placental ischemia decreases innate antioxidant activity resulting in elevated oxidative stress which appears to play a role in mediating hypertension associated with chronic RUPP in pregnant rats. PMID:18670418

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

    PubMed Central

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

    2013-01-01

    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

  2. Melatonin Reduces Oxidative Stress and Cardiovascular Changes Induced by Stanozolol in Rats Exposed to Swimming Exercise

    PubMed Central

    Barbosa dos Santos, Gustavo; Machado Rodrigues, Marcelo José; Gonçalves, Estela Maria; Cintra Gomes Marcondes, Maria Cristina; Areas, Miguel Arcanjo

    2013-01-01

    Objective: Anabolic-androgenic steroids (AAS) are nominated for clinical use to promote protein synthesis in many therapeutic conditions. However, the indiscriminate use of AAS is related to hazardous cardiac disturbances and oxidative stress. We designed a study to investigate whether prolonged treatment with high doses of stanozolol modifies the activities of some antioxidant enzymes in the heart in sedentary and trained rats and whether this treatment causes alterations of cardiovascular parameters. In addition, the effectiveness of melatonin as an antioxidant and as a modulator of the cardiovascular side effects of stanozolol (STA) treatment was analyzed. Materials and Methods: Thirty male Wistar rats were divided into the following six groups: sedentary (S), stanozolol sedentary (SS), stanozolol-melatonin sedentary (SMS), trained (T), stanozolol trained (ST) and stanozolol-melatonin trained (SMT). The stanozolol-treatment rats received 5 mg.kg?1 by subcutaneous injection before each exercise session (5 d.wk?1, i.e., 25 mg.kg?1.wk?1), while control groups received only saline solution injection. The melatonin-treatment groups received intraperitoneal injections of melatonin (10 mg.kg?1), 5 d.wk?1 for 6 wk. Electrocardiography, blood pressure and antioxidant enzyme activity measurements were performed at the end of the experimental period for cardiac function and molecular assessment. Results: This is the first time that the in vivo effects of melatonin treatment on stanozolol-induced cardiovascular side effects have been studied. Stanozolol induced bradycardia and significantly increased cardiac superoxide dismutase and catalase activities. Trained stanozolol-treated rats experienced an increase in blood pressure and relative heart weight, and they developed left cardiac axis deviation. Although melatonin did not prevent cardiac hypertrophy in exercised stanozolol-treated animals, it maintained blood pressure and cardiac catalase activity, and it prevented stanozolol-induced cardiac electrical axis deviation. Conclusion: In conclusion, under our experimental conditions, chronic stanozolol administration induced mild cardiovascular side effects that were partly attenuated by melatonin treatment. However, these results showed that the combination of melatonin and exercise could minimize the stanozolol side effects in the cardiovascular system. PMID:25610273

  3. Undifferentiated sarcoma resolved by forelimb amputation and prosthesis in a radiated tortoise (Geochelone radiata).

    PubMed

    Clabaugh, Kelleyerin; Haag, K Michelle; Hanley, Christopher S; Latimer, Kenneth S; Hernandez-Divers, Stephen J

    2005-03-01

    An adult female, radiated tortoise (Geochelone radiata) presented with a grossly swollen left forelimb that restricted mobility and prevented limb withdrawal. Clinical pathology revealed leukopenia (1.9 x 10(9)/L) and hyperproteinemia (69 g/L) that on protein electrophoresis was attributed to increased acute-phase proteins in the alpha fraction (26.4 g/L). Biopsy revealed a poorly differentiated soft tissue sarcoma. Surgical amputation at the proximal humerus was curative. To encourage postoperative mobility, a novel methylmethacrylate prosthesis, molded from a lubricated transected tennis ball, was adhered to the plastron using three cortical bone screws. This is the first recorded case of a sarcoma in the genus Geochelone. PMID:17315468

  4. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    EPA Science Inventory

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

  5. Calcium and ?-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    PubMed Central

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, ?-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or ?-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  6. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.

    PubMed

    Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

    2015-01-01

    The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1?h; ShA) or long- (12?h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence. PMID:25367502

  7. Hyperbaric oxygen treatment reduces mortality in acute iron intoxication in rats.

    PubMed

    Youngster, Ilan; Abu-Kishk, Ibrahim; Kozer, Eran; Braunstein, Rony; Bar-Haim, Adina; Berkovitch, Matitiahu

    2010-09-01

    Acute iron intoxication is one of the leading causes of overdose morbidity and mortality in children. The toxicity of iron has been postulated to be related to free radical formation and subsequent lipid peroxidation. Hyperbaric oxygen treatment can result in a number of beneficial biochemical, cellular and physiological effects, and has recently been shown to induce cellular protection against ischaemia, and in some cases against free radical formation. In the current study, we aimed to investigate the effects of hyperbaric oxygen treatment on mortality in acute iron intoxication in rats. After iron administration, 57 animals were divided into two groups: a treatment group receiving hyperbaric oxygen treatment (n = 30) and a control group (n = 27), and followed for 48 hr for signs of severe intoxication. In the second part of the study, 21 animals were divided into a treatment group receiving hyperbaric oxygen treatment (n = 10) and a control group (n = 11), and markers of oxidative stress were evaluated. We showed a significant reduction in mortality in hyperbaric oxygen-treated animals from 17 of 27 (62.9%) among untreated rats to 6 of 30 (20%). Surprisingly, in the treatment group, levels of oxidative stress markers were higher. We postulate that hyperbaric oxygen has a potentially beneficial effect in acute iron intoxication. PMID:20374236

  8. Hesperidin in orange juice reduces the absorption of celiprolol in rats.

    PubMed

    Uesawa, Yoshihiro; Mohri, Kiminori

    2008-04-01

    It has been reported that the intestinal absorption of celiprolol, an antihypertensive drug, is inhibited when it is taken with orange juice; it has been suggested that element(s) in citrus juice are responsible for this. In the present study, the pharmacokinetic interaction between celiprolol and orange juice was characterized through in vivo experiments with rats. Celiprolol 5 mg/kg was injected into the rat duodenum together with 5 ml/kg of neutralized orange juice or the same concentration of hesperidin as in the orange juice. Plasma celiprolol concentrations were measured by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Concomitant administration of orange juice or hesperidin with celiprolol significantly decreased the area under the plasma concentration-time curve (AUC) by 74% and 75%, respectively, compared with control. These findings suggest that hesperidin is responsible for the decreased absorption of celiprolol and that orange juice taken with celiprolol has an inhibiting effect on intestinal absorption of the drug. PMID:18344215

  9. Developmental Exposure to Polychlorinated Biphenyls Reduces Amphetamine Behavioral Sensitization in Long-Evans Rats

    PubMed Central

    Poon, Emily; Monaikul, Supida; Kostyniak, Paul J.; Chi, Lai Har; Schantz, Susan L.; Sable, Helen J. K.

    2013-01-01

    PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long-Evans rats were given perinatal exposure to 0, 3, or 6 mg/kg/day PCBs and behavioral sensitization to d-amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5 mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5 mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB-exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure. PMID:23623962

  10. Histamine at high dilution reduces spectral density in delta band in sleeping rats.

    PubMed

    Ruiz-Vega, G; Poitevin, B; Pérez-Ordaz, L

    2005-04-01

    Histamine is a central neurotransmitter, it increases arousal via H1 receptors. This study examines the effect of ultra-diluted histamine on arousal through changes in the sleep pattern of Wistar rats. The spectral density in delta (0.5-2.5 Hz) band, one of the three major spectral components of the sleep-electroencephalogram, was analyzed against time. Rats were randomized to receive histamine 30c (histamine 30c, 0.05 ml every 20 min during the first 2 h orally), histamine intraperitoneal pre-treatment/histamine 30c (histamine 6mg/kg i.p., followed by histamine 30c) or solvent control. The mean delta band spectral density was lower in the histamine 30c and histamine pretreatment/histamine 30c groups than the control group. Significant differences between histamine 30c and baseline during the first 2 h imply an immediate effect. These results also suggest a dynamic process in which the system spontaneously evolves between two locally stationary states according to a power law. From the time perspective, the system approaches, asymptotically, an equifinal state. PMID:15892488

  11. Rapamycin reduces burn wound progression by enhancing autophagy in deep second-degree burn in rats.

    PubMed

    Xiao, Mengjing; Li, Ligen; Hu, Quan; Ma, Li; Liu, Lingying; Chu, Wanli; Zhang, Haijun

    2013-01-01

    Burn wound progression is caused by many mechanisms including local tissue hypoperfusion, prolonged inflammation, free radical damage, apoptosis, and necrosis in burn wounds. Autophagy, a homeostatic process by which cells break down their own components, was found to protect against ischemic injury, inflammatory diseases, and apoptosis in some cases. We tested whether rapamycin, an autophagy inducer, could ameliorate burn wound progression and promote wound healing through autophagy enhancement. Using a previously described deep second-degree burn model, we first tested the effects of rapamycin on autophagic response in burn wound tissue. Autophagy levels in wound tissue of treated rats were increased as compared with controls. Furthermore, we found that laser Doppler flowmetry values and Na/K-ATPase activities were markedly higher in the treated wounds. The content of interleukin-8, methane dicarboxylic aldehyde, and myeloperoxidase activity in the wounds of treated rats were much lower than in controls. The apoptotic rates in treated wounds were much lower than controls as determined by terminal deoxynucleotidyl transferase mediated nick end labeling assay. Finally, histomorphological analysis showed that burn wound progression in the treatment group was ameliorated. The time to wound reepithelialization was shorter in the treated wounds than controls 22.5 ± 1.4 days vs. 24.8 ± 1.3 days (mean ± standard deviation, p < 0.01). PMID:23980869

  12. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats

    SciTech Connect

    Sullivan, M.F.; Ruemmler, P.S.; Ryan, J.L.

    1984-12-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and /sup 235/Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in /sup 237/Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with /sup 235/Np and either ferric or ferrous iron. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

  13. Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function

    PubMed Central

    Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J

    2012-01-01

    BACKGROUND AND PURPOSE PPAR? agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. EXPERIMENTAL APPROACH Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg?1·day?1, 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. KEY RESULTS In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI2) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. CONCLUSIONS AND IMPLICATIONS Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. PMID:22220498

  14. CD47 blockade reduces ischemia/reperfusion injury and improves survival in a rat liver transplantation model.

    PubMed

    Xiao, Zhen-Yu; Banan, Babak; Jia, Jianluo; Manning, Pamela T; Hiebsch, Ronald R; Gunasekaran, Muthukumar; Upadhya, Gundumi A; Frazier, William A; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William C

    2015-04-01

    Orthotopic liver transplantation (OLT) remains the standard treatment option for nonresponsive liver failure. Because ischemia/reperfusion injury (IRI) is an important impediment to the success of OLT, new therapeutic strategies are needed to reduce IRI. We investigated whether blocking the CD47/thrombospondin-1 inhibitory action on nitric oxide signaling with a monoclonal antibody specific to CD47 (CD47mAb400) would reduce IRI in liver grafts. Syngeneic OLT was performed with Lewis rats. Control immunoglobulin G or CD47mAb400 was administered to the donor organ at procurement or to both the organ and the recipient at the time of transplant. Serum transaminases, histological changes of the liver, and animal survival were assessed. Oxidative stress, inflammatory responses, and hepatocellular damage were also quantified. A significant survival benefit was not achieved when CD47mAb400 was administered to the donor alone. However, CD47mAb400 administration to both the donor and the recipient increased animal survival afterward. The CD47mAb400-treated group showed lower serum transaminases, bilirubin, oxidative stress, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, caspase-3 activity, and proinflammatory cytokine expression of tumor necrosis factor ?, interleukin-1?, and interleukin-6. Thus, CD47 blockade with CD47mAb400 administered both to the donor and the recipient reduced liver graft IRI in a rat liver transplantation model. This may translate to decreased liver dysfunction and increased survival of liver transplant recipients. Liver Transpl 21:468-477, 2015. © 2015 AASLD. PMID:25482981

  15. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

    PubMed Central

    Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David

    2013-01-01

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 ± 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature. PMID:23604708

  16. Inhibition of renal caveolin-1 reduces natriuresis and produces hypertension in sodium-loaded rats

    PubMed Central

    Gildea, John J.; Kemp, Brandon A.; Howell, Nancy L.; Van Sciver, Robert E.; Carey, Robert M.

    2011-01-01

    Renal dopamine receptor function and ion transport inhibition are impaired in essential hypertension. We recently reported that caveolin-1 (CAV1) and lipid rafts are necessary for normal D1-like receptor-dependent internalization of Na-K-ATPase in human proximal tubule cells. We now hypothesize that CAV1 is necessary for the regulation of urine sodium (Na+) excretion (UNaV) and mean arterial blood pressure (MAP) in vivo. Acute renal interstitial (RI) infusion into Sprague-Dawley rats of 1 ?g·kg?1·min?1 fenoldopam (FEN; D1-like receptor agonist) caused a 0.46 ± 0.15-?mol/min increase in UNaV (over baseline of 0.29 ± 0.04 ?mol/min; P < 0.01). This increase was seen in Na+-loaded rats, but not in those under a normal-sodium load. Coinfusion with ?-methyl cyclodextrin (?MCD; lipid raft disrupter, 200 ?g·kg?1·min?1) completely blocked this FEN-induced natriuresis (P < 0.001). Long-term (3 day) lipid raft disruption via continuous RI infusion of 80 ?g·kg?1·min?1 ?MCD decreased renal cortical CAV1 expression (47.3 ± 6.4%; P < 0.01) and increased MAP (32.4 ± 6.6 mmHg; P < 0.001) compared with vehicle-infused animals. To determine whether the MAP rise was due to a CAV1-dependent lipid raft-mediated disruption, Na+-loaded rats were given a bolus RI infusion of CAV1 siRNA. Two days postinfusion, cortical CAV1 expression was decreased by 73.6 ± 8.2% (P < 0.001) and the animals showed an increase in MAP by 17.4 ± 2.9 mmHg (P < 0.01) compared with animals receiving scrambled control siRNA. In summary, acute kidney-specific lipid raft disruption decreases CAV1 expression and blocks D1-like receptor-induced natriuresis. Furthermore, chronic disruption of lipid rafts or CAV1 protein expression in the kidney induces hypertension. PMID:21289050

  17. Inhibition of renal caveolin-1 reduces natriuresis and produces hypertension in sodium-loaded rats.

    PubMed

    Gildea, John J; Kemp, Brandon A; Howell, Nancy L; Van Sciver, Robert E; Carey, Robert M; Felder, Robin A

    2011-04-01

    Renal dopamine receptor function and ion transport inhibition are impaired in essential hypertension. We recently reported that caveolin-1 (CAV1) and lipid rafts are necessary for normal D(1)-like receptor-dependent internalization of Na-K-ATPase in human proximal tubule cells. We now hypothesize that CAV1 is necessary for the regulation of urine sodium (Na(+)) excretion (U(Na)V) and mean arterial blood pressure (MAP) in vivo. Acute renal interstitial (RI) infusion into Sprague-Dawley rats of 1 ?g·kg?¹·min?¹ fenoldopam (FEN; D(1)-like receptor agonist) caused a 0.46 ± 0.15-?mol/min increase in U(Na)V (over baseline of 0.29 ± 0.04 ?mol/min; P < 0.01). This increase was seen in Na(+)-loaded rats, but not in those under a normal-sodium load. Coinfusion with ?-methyl cyclodextrin (?MCD; lipid raft disrupter, 200 ?g·kg?¹·min?¹) completely blocked this FEN-induced natriuresis (P < 0.001). Long-term (3 day) lipid raft disruption via continuous RI infusion of 80 ?g·kg?¹·min?¹ ?MCD decreased renal cortical CAV1 expression (47.3 ± 6.4%; P < 0.01) and increased MAP (32.4 ± 6.6 mmHg; P < 0.001) compared with vehicle-infused animals. To determine whether the MAP rise was due to a CAV1-dependent lipid raft-mediated disruption, Na(+)-loaded rats were given a bolus RI infusion of CAV1 siRNA. Two days postinfusion, cortical CAV1 expression was decreased by 73.6 ± 8.2% (P < 0.001) and the animals showed an increase in MAP by 17.4 ± 2.9 mmHg (P < 0.01) compared with animals receiving scrambled control siRNA. In summary, acute kidney-specific lipid raft disruption decreases CAV1 expression and blocks D(1)-like receptor-induced natriuresis. Furthermore, chronic disruption of lipid rafts or CAV1 protein expression in the kidney induces hypertension. PMID:21289050

  18. North American ginseng protects against muscle damage and reduces neutrophil infiltration after an acute bout of downhill running in rats.

    PubMed

    Estaki, Mehrbod; Noble, Earl G

    2015-02-01

    Eccentric muscle contractions such as those experienced during downhill running are associated with inflammation, delayed-onset of muscle soreness, myofiber damage, and various functional deficits. North American ginseng (Panax quinquefolius L.) has been reported to possess anti-inflammatory properties and thus may offset some of this exercise-induced damage. Hence, we tested the hypothesis that intervention with North American ginseng would reduce eccentric exercise-induced muscle damage and inflammation. Male Wistar rats were fed (300 mg/(kg·day)(-1)) of either an alcohol (AL) or aqueous (AQ) extract of North American ginseng for 14 days before a single bout of downhill running and were compared with matching nonexercised (C) groups. Plasma creatine kinase levels were significantly reduced in both ginseng treated groups compared with the C group that received a water placebo (p < 0.002). Further, the AQ but not AL group also showed attenuated morphological signs of damage (hemotoxylin and eosin) as well as reduced levels of infiltrating neutrophils (HIS48) in the soleus muscle (p < 0.001). In summary, supplementation with an AQ but not AL extract of North American ginseng was able to reduce eccentric exercise-induced muscle damage and inflammation. PMID:25531801

  19. Exercise-Induced Neuroprotection in the Spastic Han Wistar Rat: The Possible Role of Brain-Derived Neurotrophic Factor

    PubMed Central

    Van Kummer, Brooke H.; Cohen, Randy W.

    2015-01-01

    Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF) and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection. PMID:25710032

  20. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia

    PubMed Central

    Candelario-Jalil, Eduardo; de Oliveira, Antonio C Pinheiro; Gräf, Sybille; Bhatia, Harsharan S; Hüll, Michael; Muñoz, Eduardo; Fiebich, Bernd L

    2007-01-01

    Background Neuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti-inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E2 (PGE2) and 8-iso-prostaglandin F2? (8-iso-PGF2?) production by lipopolysaccharide (LPS)-activated primary rat microglia. Methods Primary microglial cell cultures were prepared from cerebral cortices of neonatal rats. Microglial cells were stimulated with 10 ng/ml of LPS in the presence or absence of different concentrations of resveratrol (1–50 ?M). After 24 h incubation, culture media were collected to measure the production of PGE2 and 8-iso-PGF2? using enzyme immunoassays. Protein levels of COX-1, COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) were studied by Western blotting after 24 h of incubation with LPS. Expression of mPGES-1 at the mRNA level was investigated using reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results Our results indicate that resveratrol potently reduced LPS-induced PGE2 synthesis and the formation of 8-iso-PGF2?, a measure of free radical production. Interestingly, resveratrol dose-dependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme responsible for the synthesis of PGE2 by activated microglia, whereas resveratrol did not affect the expression of COX-2. Resveratrol is therefore the first known inhibitor which specifically prevents mPGES-1 expression without affecting COX-2 levels. Another important observation of the present study is that other COX-1 selective inhibitors (SC-560 and Valeroyl Salicylate) potently reduced PGE2 and 8-iso-PGF2? production by LPS-activated microglia. Conclusion These findings suggest that the naturally occurring polyphenol resveratrol is able to reduce microglial activation, an effect that might help to explain its neuroprotective effects in several in vivo models of brain injury. PMID:17927823

  1. Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats

    PubMed Central

    2012-01-01

    Background Diets producing a high glycemic response result in exaggerated insulin secretion which induces hepatic lipogenesis, contributing to development of insulin resistance and fatty liver. Viscous dietary fibers blunt the postprandial rise in blood glucose, however their effect on type 2 diabetes and obesity are not entirely known. This study examined the effect of chronic consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids in an obese diabetic rat model. Methods Three groups of Zucker Diabetic Fatty (ZDF) rats were fed diets containing either 5% non-viscous cellulose (control), low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HV- HPMC) for six weeks. Zucker lean littermates consuming cellulose served as a negative control. Markers of glucose control, including oral glucose tolerance test, glycated hemoglobin and urinary glucose, were measured as well as adiposity and the accumulation of liver lipids. Results The HPMC diets increased the viscosity of the small intestinal contents and reduced the postprandial rise in blood glucose. The food efficiency ratio was greater with HPMC feeding compared to the obese control and urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups had lower glycated hemoglobin and kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC group compared to the obese control group. The HV-HPMC group also had lower concentrations of liver lipid and cholesterol and reduced liver weight. However, HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle concentration of acylcarnitines, a lipid intermediate in fatty acid ?-oxidation, was not different between the HPMC groups and obese control, suggesting no change in muscle fatty acid oxidation by HPMC. Conclusions Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting, improved glucose control and reduced insulin resistance and fatty liver in a model of obesity with diabetes. PMID:23146593

  2. Role of glucocorticoids in the response of rat leg muscles to reduced activity

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Tischler, Marc E.

    1986-01-01

    Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

  3. Alpha-tocopherol reduces doxorubicin-induced toxicity in rats--histological and biochemical evidences.

    PubMed

    Geetha, A; Sankar, R; Marar, T; Devi, C S

    1990-04-01

    The beneficial effect of alpha-tocopherol on doxorubicin-induced toxicity was studied in rats. alpha-Tocopherol (400 mg/kg/day) was administered orally, daily for a period of 2 months along with/without doxorubicin (2.5 mg/kg, i v weekly once for 8 weeks). Histology showed liver necrosis, heart myocyte degeneration, glomerular and tubular degeneration, cellular infiltration and desquammation of intestinal mucosa in doxorubicin treated animals. There was a significant increase in lipid peroxide levels measured in terms of "TBA reactants" in all these organs. These changes were associated with elevated levels of serum enzymes such as transaminases, creatine kinase and lactate dehydrogenase. The pathological observations, were minimal in animals receiving both doxorubicin and alpha-tocopherol. The lipid peroxide levels were low with concomitant normal levels of serum and intestinal enzymes in those animals. PMID:2174831

  4. Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats

    PubMed Central

    Wilson, Gabriel J.; Layman, Donald K.; Moulton, Christopher J.; Norton, Layne E.; Anthony, Tracy G.; Proud, Christopher G.; Rupassara, S. Indu; Garlick, Peter J.

    2015-01-01

    Muscle protein synthesis (MPS) increases after consumption of a protein-containing meal but returns to baseline values within 3 h despite continued elevations of plasma amino acids and mammalian target of rapamycin (mTORC1) signaling. This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal. Male Sprague-Dawley rats (~270 g) trained to consume three meals daily were food deprived for 12 h, and then blood and gastrocnemius muscle were collected 0, 90, or 180 min after a standard 4-g test meal (20% whey protein). At 135 min postmeal, rats were orally administered 2.63 g of CHO, 270 mg of Leu, both, or water (sham control). Following test meal consumption, MPS peaked at 90 min and then returned to basal (time 0) rates at 180 min, although ribosomal protein S6 kinase and eIF4E-binding protein-1 phosphorylation remained elevated. In contrast, rats administered Leu and/or CHO supplements at 135 min postmeal maintained peak MPS through 180 min. MPS was inversely associated with the phosphorylation states of translation elongation factor 2, the “cellular energy sensor” adenosine monophosphate-activated protein kinase-? (AMPK?) and its substrate acetyl-CoA carboxylase, and increases in the ratio of AMP/ATP. We conclude that the incongruity between MPS and mTORC1 at 180 min reflects a block in translation elongation due to reduced cellular energy. Administering Leu or CHO supplements ~2 h after a meal maintains cellular energy status and extends the postprandial duration of MPS. PMID:21917636

  5. Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

    PubMed Central

    Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

    1989-01-01

    The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

  6. High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague-Dawley rats.

    PubMed

    Cudnoch-Jedrzejewska, Agnieszka; Gomolka, Ryszard; Szczepanska-Sadowska, Ewa; Czarzasta, Katarzyna; Wrzesien, Robert; Koperski, Lukasz; Puchalska, Liana; Wsol, Agnieszka

    2015-01-01

    Central application of apelin elevates blood pressure and influences neuroendocrine responses to stress and food consumption. However, it is not known whether the central cardiovascular effects of apelin depend also on caloric intake or chronic stress. The purpose of the present study was to determine the effects of intracerebroventricular administration of apelin on blood pressure (mean arterial blood pressure) and heart rate in conscious Sprague-Dawley rats consuming either a normal-fat diet (NFD) or high-fat diet (HFD) for 12 weeks. During the last 4 weeks of the food regime, the rats were exposed (NFDS and HFDS groups) or not exposed (NFDNS and HFDNS groups) to chronic stress. Each group was divided into two subgroups receiving intracerebroventricular infusions of either vehicle or apelin. Apelin elicited significant increase of mean arterial blood pressure and heart rate in the NFDNS rats. This effect was abolished in the HFDNS, HFDS and NFDS groups. HFD resulted in a significant elevation of blood concentrations of total cholesterol, triglycerides glucose and insulin. Chronic stress reduced plasma concentration of total and high-density lipoprotein cholesterol, and increased plasma corticosterone concentration and APJ receptor mRNA expression in the hypothalamus, whereas a combination of a HFD with chronic stress resulted in the elevation of plasma triglycerides, total cholesterol and low-density lipoprotein cholesterol, and in increased plasma corticosterone concentration, apelin concentration and APJ receptor mRNA expression in the hypothalamus. It is concluded that a HFD and chronic stress result in significant suppression of the central pressor action of apelin, and cause significant though not unidirectional changes of metabolic and endocrine parameters. PMID:25311903

  7. Electrographic seizures are significantly reduced by in vivo inhibition of neuronal uptake of extracellular glutamine in rat hippocampus

    PubMed Central

    Kanamori, Keiko; Ross, Brian D.

    2013-01-01

    Summary Rats were given unilateral kainate injection into hippocampal CA3 region, and the effect of chronic electrographic seizures on extracellular glutamine (GLNECF) was examined in those with low and steady levels of extracellular glutamate (GLUECF). GLNECF, collected by microdialysis in awake rats for 5 h, decreased to 62 ± 4.4% of the initial concentration (n = 6). This change correlated with the frequency and magnitude of seizure activity, and occurred in the ipsilateral but not in contralateral hippocampus, nor in kainate-injected rats that did not undergo seizure (n = 6). Hippocampal intracellular GLN did not differ between the Seizure and No-Seizure Groups. These results suggested an intriguing possibility that seizure-induced decrease of GLNECF reflects not decreased GLN efflux into the extracellular fluid, but increased uptake into neurons. To examine this possibility, neuronal uptake of GLNECF was inhibited in vivo by intrahippocampal perfusion of 2-(methylamino)isobutyrate, a competitive and reversible inhibitor of the sodium-coupled neutral amino acid transporter (SNAT) subtypes 1 and 2, as demonstrated by 1.8 ± 0.17 fold elevation of GLNECF (n = 7). The frequency of electrographic seizures during uptake inhibition was reduced to 35 ± 7% (n = 7) of the frequency in pre-perfusion period, and returned to 88 ± 9% in the post-perfusion period. These novel in vivo results strongly suggest that, in this well-established animal model of temporal-lobe epilepsy, the observed seizure-induced decrease of GLNECF reflects its increased uptake into neurons to sustain enhanced glutamatergic epileptiform activity, thereby demonstrating a possible new target for anti-seizure therapies. PMID:24070846

  8. Reducing hemorrhagic complication by dabigatran via neurovascular protection after recanalization with tissue plasminogen activator in ischemic stroke of rat.

    PubMed

    Kono, Syoichiro; Deguchi, Kentaro; Omote, Yoshio; Yunoki, Taijun; Yamashita, Toru; Kurata, Tomoko; Ikeda, Yoshio; Abe, Koji

    2014-01-01

    This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study. PMID:24265137

  9. Nitric oxide-releasing flurbiprofen reduces formation of proinflammatory hydrogen sulfide in lipopolysaccharide-treated rat

    PubMed Central

    Anuar, Farhana; Whiteman, Matthew; Siau, Jia Ling; Kwong, Shing Erl; Bhatia, Madhav; Moore, Philip K

    2006-01-01

    The biosynthesis of both nitric oxide (NO) and hydrogen sulfide (H2S) is increased in lipopolysaccharide (LPS)-injected mice and rats but their interaction in these models is not known. In this study we examined the effect of the NO donor, nitroflurbiprofen (and the parent molecule flurbiprofen) on NO and H2S metabolism in tissues from LPS-pretreated rats. Administration of LPS (10?mg?kg?1, i.p.; 6?h) resulted in an increase (P<0.05) in plasma TNF-?, IL-1? and nitrate/nitrite (NOx) concentrations, liver H2S synthesis (from added cysteine), CSE mRNA, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO) activity (marker for neutrophil infiltration) and nuclear factor-kappa B (NF-?B) activation. Nitroflurbiprofen (3–30?mg?kg?1, i.p.) administration resulted in a dose-dependent inhibition of the LPS-mediated increase in plasma TNF-?, IL-1? and NOx concentration, liver H2S synthesis (55.00±0.95?nmole?mg?protein?1, c.f. 62.38±0.47?nmole?mg?protein?1, n=5, P<0.05), CSE mRNA, iNOS, MPO activity and NF-?B activation. Flurbiprofen (21?mg?kg?1, i.p.) was without effect. These results show for the first time that nitroflurbiprofen downregulates the biosynthesis of proinflammatory H2S and suggest that such an effect may contribute to the augmented anti-inflammatory activity of this compound. These data also highlight the existence of ‘crosstalk' between NO and H2S in this model of endotoxic shock. PMID:16491094

  10. Olfactory ensheathing cells reduce duration of autonomic dysreflexia in rats with high spinal cord injury.

    PubMed

    Kalincík, Tomás; Choi, Eun A; Féron, François; Bianco, John; Sutharsan, Ratneswary; Hayward, Ian; Mackay-Sim, Alan; Carrive, Pascal; Waite, Phil M E

    2010-04-19

    Autonomic dysreflexia is a common complication in high spinal cord injury and can result in serious consequences and death. Here we have examined the effect of acute transplantation of olfactory ensheathing cells on cardiovascular functions in rats. After T4 transection, radio-telemetric recording in conscious animals was used to study blood pressure and heart rate at rest and during autonomic dysreflexia for up to 8 weeks post-injury. Olfactory ensheathing cells from syngeneic rats were transplanted at the injury site; control animals received culture medium only. At the study end point, we examined morphometric features of sympathetic preganglionic neurons above and below the injury. T4 transection resulted in a fall in resting mean arterial pressure and an increase in resting heart rate. Colorectal distension, used to trigger autonomic dysreflexia, caused episodic hypertension and bradycardia. Although the cell transplantation had no effect on resting cardiovascular parameters, it led to a significantly faster recovery from hypertension, with the recovery time shortened by approximately 25%. The transection resulted in an increase in soma size of sympathetic preganglionic neurons above and below the injury. OEC transplantation normalised this change below the injury and increased dendritic length of preganglionic neurons above the injury, compared to controls. It has been proposed that changes in sympathetic preganglionic neurons following spinal cord transection may be related to the development of autonomic dysreflexia. Our results suggest that olfactory ensheathing cells may alter the morphology of these neurons, and hence modify their activity in the neuronal networks responsible for the dysreflexic reaction. PMID:19896908

  11. Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.

    PubMed

    Abe, Chikara; Nagai, Yuko; Yamaguchi, Aoi; Aoki, Hitomi; Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Sugimachi, Masaru; Morita, Hironobu

    2015-04-15

    Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats. PMID:25681426

  12. Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats

    PubMed Central

    2014-01-01

    Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

  13. Influence of oxidizing or reducing agents on gastrointestinal absorption of U, Pu, Am, Cm and Pm by rats

    SciTech Connect

    Sullivan, M.F.; Ruemmler, P.S.; Ryan, J.L.; Buschbom, R.L.

    1986-02-01

    Absorption of 233U, 238Pu, 241Am, and 244Cm from the gastrointestinal (GI) tract was measured in rats, fed ad libitum or fasted, that were gavaged with solutions containing ferric iron, ferrous iron, iron powder, quinhydrone or ascorbic acid. Absorption and retention of all of these actinides was increased substantially by fasting and by the addition of mild oxidizing agents, ferric iron and quinhydrone. In contrast, absorption and retention were decreased to below the fasted level by all the reducing agents except ascorbic acid, which caused diarrhea and an increase in absorption. Absorption of the lanthanide element 147Pm from the intestine of fasted rats was also increased by ferric iron. Some of these actinide elements are polyvalent and are, in some cases, known to be absorbed from the GI tract more readily in their higher oxidation states. This suggested an oxidation-reduction mechanism for the effect of fasting and the action of the chemical agents used. However, the improbability that either 241Am(III) 244Cm(III) or 147Pm is converted to a different oxidation state under these conditions makes that mechanism unlikely. Other explanations are suggested.

  14. Influence of oxidizing or reducing agents on gastrointestinal absorption of U, Pu, Am, Cm and Pm by rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Ryan, J L; Buschbom, R L

    1986-02-01

    Absorption of 233U, 238Pu, 241Am, and 244Cm from the gastrointestinal (GI) tract was measured in rats, fed ad libitum or fasted, that were gavaged with solutions containing ferric iron, ferrous iron, iron powder, quinhydrone or ascorbic acid. Absorption and retention of all of these actinides was increased substantially by fasting and by the addition of mild oxidizing agents, ferric iron and quinhydrone. In contrast, absorption and retention were decreased to below the fasted level by all the reducing agents except ascorbic acid, which caused diarrhea and an increase in absorption. Absorption of the lanthanide element 147Pm from the intestine of fasted rats was also increased by ferric iron. Some of these actinide elements are polyvalent and are, in some cases, known to be absorbed from the GI tract more readily in their higher oxidation states. This suggested an oxidation-reduction mechanism for the effect of fasting and the action of the chemical agents used. However, the improbability that either 241Am(III) 244Cm(III) or 147Pm is converted to a different oxidation state under these conditions makes that mechanism unlikely. Other explanations are suggested. PMID:3005196

  15. Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

    PubMed

    Erdely, Aaron; Antonini, James M; Young, Shih-Houng; Kashon, Michael L; Gu, Ja K; Hulderman, Tracy; Salmen, Rebecca; Meighan, Terence; Roberts, Jenny R; Zeidler-Erdely, Patti C

    2014-01-01

    Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

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

    PubMed Central

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

    2013-01-01

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

  17. Protection against nitric oxide-induced apoptosis in rat mesangial cells demands mitogen-activated protein kinases and reduced glutathione.

    PubMed

    Sandau, K B; Callsen, D; Brüne, B

    1999-10-01

    Inflammatory diseases such as proliferative glomerulonephritis are associated with the production of nitric oxide (NO), which can initiate apoptotic/necrotic cell death. We studied the role of the p42/44 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal kinases1/2 (JNK1/2) in NO-evoked cytotoxicity in rat mesangial cells (MC). The NO donor S-nitrosoglutathione time- and concentration-dependently promoted apoptotic cell death as detected by JNK1/2 and caspase-3 activation as well as DNA fragmentation. By using Ro 318220, a JNK1/2 activator, we established a correlation between apoptosis and JNK1/2 activation. Apoptosis is antagonized by the addition of fetal calf serum or the simultaneous generation of NO and superoxide (O(2)(-)), another biological inflammatory mediator. Fetal calf serum-induced protection required p42/44 MAPK activation as inhibition of the p42/44 MAPK pathway by the MAPK kinase-1 inhibitor PD 98059 attenuated MC protection. In contrast, cytoprotection by NO/O(2)(-) cogeneration demanded reduced glutathione but was p42/44 MAPK unrelated. Depletion of glutathione reversed NO/O(2)(-)-evoked survival to cell destruction and reinstalled JNK1/2 activity. In conclusion, different signal transduction pathways facilitate protection against NO-induced JNK1/2 activation and apoptosis in rat MC. PMID:10496957

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

    PubMed Central

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

    2011-01-01

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

  19. Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia

    PubMed Central

    Ibebunjo, Chikwendu; Chick, Joel M.; Kendall, Tracee; Eash, John K.; Li, Christine; Zhang, Yunyu; Vickers, Chad; Wu, Zhidan; Clarke, Brian A.; Shi, Jun; Cruz, Joseph; Fournier, Brigitte; Brachat, Sophie; Gutzwiller, Sabine; Ma, QiCheng; Markovits, Judit; Broome, Michelle; Steinkrauss, Michelle; Skuba, Elizabeth; Galarneau, Jean-Rene; Gygi, Steven P.

    2013-01-01

    Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia. PMID:23109432

  20. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats.

    PubMed

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R; Taché, Yvette

    2013-09-15

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

  1. Corticosterone induces steroidogenic lesion in cultured adult rat Leydig cells by reducing the expression of star protein and steroidogenic enzymes.

    PubMed

    Rengarajan, Srinivasan; Balasubramanian, Karundevi

    2008-04-01

    The present study was designed to investigate the dose-dependent direct effect of corticosterone on adult rat Leydig cell steroidogenesis in vitro. Leydig cells were isolated from the testis of normal adult male albino rats, purified on discontinuous Percoll gradient and plated in culture plates/flasks overnight at 34 degrees C in a CO(2) incubator under 95% air and 5% CO(2) using DME/F12 medium containing 1% fetal bovine serum. After the attachment of cells, serum-containing medium was removed and cells were exposed to different doses (0, 50, 100, 200, 400, and 800 nM) of corticosterone using serum-free fresh medium for 24 h at 34 degrees C. At the end of exposure period, cells were utilized for assessment of the activities and mRNA expression of steroidogenic enzymes (cytochrome P(450) side chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and cytochrome P(450) aromatase) and steroidogenic acute regulatory protein gene expression. Testosterone and estradiol production were also quantified. Activities of cytochrome P(450) side chain cleavage enzyme, 3beta- and 17beta-hydroxysteroid dehydrogenases were declined significantly in a dose-dependent manner after corticosterone exposure, while their mRNA expression were significantly reduced at higher doses of corticosterone exposure. The activity and mRNA expression of cytochrome P(450) aromatase registered a significant increase at 100 nM dose of corticosterone whereas at 200-800 nM doses both the activity as well as the mRNA levels was significantly reduced below the basal level. StAR protein gene expression was significantly inhibited by higher doses of corticosterone employed. At all doses employed, corticosterone significantly reduced the production of testosterone by Leydig cells, while estradiol level registered a significant increase at 50 and 100 nM doses but at higher doses, it registered a significant decrease when compared to basal level. It is concluded from the present in vitro study that the molecular mechanism by which corticosterone reduces the production of Leydig cell testosterone is by reducing the activities and mRNA expression of steroidogenic enzymes and steroidogenic acute regulatory protein. PMID:17849416

  2. Orally administered ginseng extract reduces serum total cholesterol and triglycerides that induce fatty liver in 66% hepatectomized rats.

    PubMed

    Cui, X; Sakaguchi, T; Ishizuka, D; Tsukada, K; Hatakeyama, K

    1998-01-01

    The effects of ginseng extract (from the root of Panax ginseng) on factors inducing fatty liver were examined in 66% hepatectomized rats. Oral administration of ginseng extract at 125 or 250 mg/kg/day produced statistically significant reductions in total cholesterol and triglyceride concentrations in the blood 3 days after hepatectomy (P<0.05); the total cholesterol response appeared to be dose-related. Administration of ginseng extract at both doses also reduced total cholesterol and triglyceride concentrations in the liver 3 days after hepatectomy. Food intake and serum chemistry parameters indicating liver and kidney function were unchanged after ginseng administration except for the lipid metabolic parameters. These observations suggest that orally administered ginseng extract can suppress the formation of fatty liver after hepatic resection. PMID:9818784

  3. Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats.

    PubMed

    Cerf, Marlon E; Chapman, Charna S; Muller, Christo J; Louw, Johan

    2009-12-01

    Hyperglycemia and compromised beta-cell development were demonstrated in neonatal rats programmed with a gestational high-fat diet. The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. Fetuses were maintained, via maternal nutrition, on either a standard laboratory diet (control) or a high-fat diet throughout gestation (HFG). Pancreata from 1-day-old neonates were excised for islet isolation and the subsequent measurement of insulin release at 2.8, 6.5, 13, and 22 mmol/L glucose. Other pancreata were either snap frozen for quantitative polymerase chain reaction or formalin fixed for immunohistochemistry followed by image analysis. The HFG neonates had reduced insulin release at 13- and 22-mmol/L glucose concentrations. No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. PMID:19604517

  4. Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability.

    PubMed

    Youssef, Farid F

    2015-03-01

    Calorie restriction and the ketogenic diet have been successfully used in models of neuroprotection. However, there are limitations in clinical application of these diets and attention has turned to understanding their mechanism of action. Ketone bodies are produced in both diets and maybe involved in their ability to attenuate neuronal injury. This study seeks to assess the effects of ketone bodies on neuronal transmission and their efficacy in reducing the impact of known excitotoxins. We made use of extracellular recordings from rat hippocampal slices and demonstrate that ketone bodies had no effect on neuronal transmission or induction of long-term potentiation (LTP). Perfusion of slices with N-methyl-d-aspartate (NMDA, 15 ?M) produced neuronal depression suggestive of cell injury (antidromic recording also demonstrated similar depression), such that recovery of population spike potentials after 60 minutes was 27% in normal (10 mM) glucose but only 7% during reduced (2·5 mM) glucose availability. Experiments in ketone bodies demonstrated improved recovery (31%) but only under conditions of low glucose. Similarly, there was enhanced recovery of slices treated with kainic acid (KA, 30 ?M) in reduced glucose media (13-27%), but no difference in normal glucose. These findings suggest that ketone bodies do not alter neuronal function but can alter the response to excitotoxins when energy supplies are impaired, probably by acting as an alternative energy substrate. PMID:25082548

  5. PPAR? activation blocks development and reduces established neuropathic pain in rats.

    PubMed

    Morgenweck, J; Griggs, R B; Donahue, R R; Zadina, J E; Taylor, B K

    2013-07-01

    Peroxisome proliferator-activated receptor gamma (PPAR?) is emerging as a new pharmacotherapeutic target for chronic pain. When oral (3-30 mg/kg/day in chow for 7 wk) or twice-daily intraperitoneal (1-10 mg/kg/day for 2 wk) administration began before spared nerve injury (SNI), pioglitazone, a PPAR? agonist, dose-dependently prevented multiple behavioral signs of somatosensory hypersensitivity. The highest dose of intraperitoneal pioglitazone did not produce ataxia or reductions in transient mechanical and heat nociception, indicating that inhibitory effects on hypersensitivity were not secondary to adverse drug-induced behaviors or antinociception. Inhibitory effects on hypersensitivity persisted at least one week beyond cessation of pioglitazone administration, suggestive of long-lasting effects on gene expression. Blockade of PPAR? with GW9662, an irreversible and selective PPAR? antagonist, dose-dependently reduced the inhibitory effect of pioglitazone on hypersensitivity, indicating a PPAR?-dependent action. Remarkably, a single preemptive injection of pioglitazone 15 min before SNI attenuated hypersensitivity for at least 2 weeks; this was enhanced with a second injection delivered 12 h after SNI. Pioglitazone injections beginning after SNI also reduced hypersensitivity, albeit to a lesser degree than preemptive treatment. Intraperitoneal pioglitazone significantly reduced the nerve injury-induced up-regulation of cd11b, GFAP, and p-p38 in the dorsal horn, indicating a mechanism of action involving spinal microglia and/or astrocyte activation. Oral pioglitazone significantly reduced touch stimulus-evoked phospho-extracellular signal-related kinase (p-ERK) in lamina I-II, indicating a mechanism of action involving inhibition of central sensitization. We conclude that pioglitazone reduces spinal glial and stimulus-evoked p-ERK activation and that PPAR? activation blocks the development of and reduces established neuropathic pain. PMID:23415633

  6. PPAR? activation blocks development and reduces established neuropathic pain in rats

    PubMed Central

    Morgenweck, J.; Griggs, R.B.; Donahue, R.R.; Zadina, J.E.; Taylor, B.K.

    2013-01-01

    Peroxisome proliferator-activated receptor gamma (PPAR?) is emerging as a new pharmacotherapeutic target for chronic pain. When oral (3–30 mg/kg/day in chow for 7 wk) or twice-daily intraperitoneal (1–10 mg/kg/day for 2 wk) administration began before spared nerve injury (SNI), pioglitazone, a PPAR? agonist, dose-dependently prevented multiple behavioral signs of somatosensory hypersensitivity. The highest dose of intraperitoneal pioglitazone did not produce ataxia or reductions in transient mechanical and heat nociception, indicating that inhibitory effects on hypersensitivity were not secondary to adverse drug-induced behaviors or antinociception. Inhibitory effects on hypersensitivity persisted at least one week beyond cessation of pioglitazone administration, suggestive of long-lasting effects on gene expression. Blockade of PPAR? with GW9662, an irreversible and selective PPAR? antagonist, dose-dependently reduced the inhibitory effect of pioglitazone on hypersensitivity, indicating a PPAR?-dependent action. Remarkably, a single preemptive injection of pioglitazone 15 min before SNI attenuated hypersensitivity for at least 2 weeks; this was enhanced with a second injection delivered 12 hr after SNI. Pioglitazone injections beginning after SNI also reduced hypersensitivity, albeit to a lesser degree than preemptive treatment. Intraperitoneal pioglitazone significantly reduced the nerve injury-induced up-regulation of cd11b, GFAP, and p-p38 in the dorsal horn, indicating a mechanism of action involving spinal microglia and/or astrocyte activation. Oral pioglitazone significantly reduced touch stimulus-evoked phospho-extracellular signal-related kinase (p-ERK) in lamina I-II, indicating a mechanism of action involving inhibition of central sensitization. We conclude that pioglitazone reduces spinal glial and stimulus-evoked p-ERK activation and that PPAR? activation blocks the development of and reduces established neuropathic pain. PMID:23415633

  7. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats.

    PubMed

    Hansen, Rikke R; Erichsen, Helle K; Brown, David T; Mirza, Naheed R; Munro, Gordon

    2012-12-01

    GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-?2 and -?3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary mechanical hypersensitivity. The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical hypersensitivity (180 min post-injection). However, the low efficacy subtype-selective PAM TPA023 (3-30 mg/kg) was completely ineffective. This was surprising as both NS11394 and TPA023 robustly attenuated late phase (6-30 min post-injection) capsaicin-induced flinching, a pain-like behaviour that is putatively driven by peripheral and central sensitizing mechanisms. Diazepam also attenuated capsaicin-induced nocifensive behaviours, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human volunteer studies. PMID:22985969

  8. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    PubMed

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, ?-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ? 0.001) and glutamate (467%, p ? 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. PMID:25578265

  9. Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons

    PubMed Central

    Dang, Khoa; Bielefeldt, Klaus

    2013-01-01

    Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6–S2) or thoracolumbar (TL, T13–L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis. PMID:23636721

  10. Lysine and Arginine Reduce the Effects of Cerebral Ischemic Insults and Inhibit Glutamate-Induced Neuronal Activity in Rats

    PubMed Central

    Kondoh, Takashi; Kameishi, Makiko; Mallick, Hruda Nanda; Ono, Taketoshi; Torii, Kunio

    2010-01-01

    Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0?g/kg), arginine (0.6?g/kg), or their combined administration (0.6?g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6?g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects. PMID:20589237

  11. Low-Level Laser Therapy (808 nm) Reduces Inflammatory Response and Oxidative Stress in Rat Tibialis Anterior Muscle After Cryolesion

    PubMed Central

    Assis, Lívia; Moretti, Ana I.S.; Abrahão, Thalita B.; Cury, Vivian; Souza, Heraldo P.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2012-01-01

    Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n = 20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808 nm, tip area of 0.00785 cm2, power 30 mW, application time 47 seconds, fluence 180 J/cm2; 3.8 mW/cm2; and total energy 1.4 J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-k? and COX-2 and by TNF-? and IL-1? concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. PMID:23001637

  12. SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes.

    PubMed

    Rainbow, R D; Lodwick, D; Hudman, D; Davies, N W; Norman, R I; Standen, N B

    2004-06-15

    C-terminal fragments of the sulphonylurea receptor SUR2A can alter the functional expression of cloned ATP-sensitive K(+) channels (K(ATP)). To investigate the protective role of K(ATP) channels during metabolic stress we transfected SUR2A fragments into adult rat cardiac myocytes. A fragment comprising residues 1294-1358, the A-fragment, reduced sarcolemmal K(ATP) currents by over 85% after 2 days (pinacidil-activated current densities were: vector alone 7.04 +/- 1.22; and A-fragment 0.94 +/- 0.07 pA pF(-1), n= 6,6, P < 0.001). An inactive fragment (1358-1545, current density 6.30 +/- 0.85 pA pF(-1), n= 6) was used as a control. During metabolic inhibition (CN and iodoacetate) of isolated myocytes stimulated at 1 Hz, the A-fragment delayed action potential shortening and contractile failure, but accelerated rigor contraction and increased Ca(2+) loading. On reperfusion, A-fragment-transfected cells also showed increased intracellular Ca(2+) and the proportion of cells recovering contractile function was reduced from 40.0 to 9.5% (P < 0.01). The protective effect of pretreatment with 2,4-dinitrophenol, measured from increased functional recovery and reduced Ca(2+) loading, was abolished by the A-fragment. Our data are consistent with a role for K(ATP) channels in causing action potential failure and reduced Ca(2+) loading during metabolic stress, and with a major role in protection by preconditioning. The effects of the A-fragment may arise entirely from reduced expression of the sarcolemmal K(ATP) channel, but we also discuss the possibility of mitochondrial effects. PMID:15020694

  13. SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes

    PubMed Central

    Rainbow, RD; Lodwick, D; Hudman, D; Davies, NW; Norman, RI; Standen, NB

    2004-01-01

    C-terminal fragments of the sulphonylurea receptor SUR2A can alter the functional expression of cloned ATP-sensitive K+ channels (KATP). To investigate the protective role of KATP channels during metabolic stress we transfected SUR2A fragments into adult rat cardiac myocytes. A fragment comprising residues 1294–1358, the A-fragment, reduced sarcolemmal KATP currents by over 85% after 2 days (pinacidil-activated current densities were: vector alone 7.04 ± 1.22; and A-fragment 0.94 ± 0.07 pA pF?1, n = 6,6, P < 0.001). An inactive fragment (1358–1545, current density 6.30 ± 0.85 pA pF?1, n = 6) was used as a control. During metabolic inhibition (CN and iodoacetate) of isolated myocytes stimulated at 1 Hz, the A-fragment delayed action potential shortening and contractile failure, but accelerated rigor contraction and increased Ca2+ loading. On reperfusion, A-fragment-transfected cells also showed increased intracellular Ca2+ and the proportion of cells recovering contractile function was reduced from 40.0 to 9.5% (P < 0.01). The protective effect of pretreatment with 2,4-dinitrophenol, measured from increased functional recovery and reduced Ca2+ loading, was abolished by the A-fragment. Our data are consistent with a role for KATP channels in causing action potential failure and reduced Ca2+ loading during metabolic stress, and with a major role in protection by preconditioning. The effects of the A-fragment may arise entirely from reduced expression of the sarcolemmal KATP channel, but we also discuss the possibility of mitochondrial effects. PMID:15020694

  14. Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor ?4 Subunit Upregulation

    PubMed Central

    Hsu, Fu-Chun; Smith, Sheryl S.

    2010-01-01

    Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3?-OH-5?-pregnan-20-one (3?,5?-THP). This 3?,5?-THP withdrawal also results in a decreased decay time constant for GABA-gated current assessed using whole cell patch-clamp techniques on pyramidal cells acutely dissociated from CA1 hippocampus. The purpose of this study was to test the hypothesis that the decreases in total integrated GABA-gated current observed at the level of the isolated pyramidal cell would be manifested as a reduced GABA inhibition at the circuit level following hormone withdrawal. Toward this end, adult, female rats were administered P via subcutaneous capsule for 3 wk using a multiple withdrawal paradigm. We then evaluated paired-pulse inhibition (PPI) of pyramidal neurons in CA1 hippocampus using extracellular recording techniques in hippocampal slices from rats 24 h after removal of the capsule (P withdrawal, P Wd). The population spike (PS) was recorded at the stratum pyramidale following homosynaptic orthodromic stimulation in the nearby stratum radiatum. The threshold for eliciting a response was decreased after P Wd, and the mean PS amplitude was significantly increased compared with control values at this time. Paired pulses with 10-ms inter-pulse intervals were then applied across an intensity range from 2 to 20 times threshold. Evaluation of paired-pulse responses showed a significant 40–50% reduction in PPI for PS recorded in the hippocampal CA1 region after P Wd, suggesting an increase in circuit excitability. At this time, enhancement of PPI by the benzodiazepine lorazepam (LZM; 10 µM) was prevented, while pentobarbital (10 µM) potentiation of PPI was comparable to control levels of response. These data are consistent with upregulation of the ?4 subunit of the GABAA receptor (GABAR) as we have previously shown. Moreover, the reduced PPI caused by P Wd was prevented by suppression of GABAR ?4-subunit expression following intraventricular administration of specific anti-sense oligonucleotides (1 µg/h for 72 h). These results demonstrating a reduction in PPI following P Wd suggest that GABAergic-mediated recurrent or feed-forward inhibition occurring at the circuit level were decreased following P Wd in female rats, an effect at least partially attributable to alterations in the GABAR subunit gene expression. PMID:12522171

  15. NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat.

    PubMed

    Zhao, Z; Cheng, M; Maples, K R; Ma, J Y; Buchan, A M

    2001-08-01

    Free radicals have gained wide acceptance as mediators of cerebral ischemic injury. It has previously been reported that a spin trap nitrone, alpha-phenyl-N-tert-butyl nitrone (PBN), can reduce infarct volumes in rats subjected to either permanent or transient focal cerebral ischemia. A recent study has demonstrated that NXY-059, a novel free radical trapping nitrone compound, has a neuroprotective effect against transient focal cerebral ischemia. This study was designed to determine the effect of NXY-059 in a rodent model of permanent focal cerebral ischemia. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion (MCAO) by placement of a microaneurysm clip on the middle cerebral artery (MCA). Animals were divided into three groups: (1) physiological saline given as a 1 ml/kg i.v. bolus administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 0.5 ml/h of physiological saline for 24 h (n=10); (2) 30 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 30 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=9); (3) 60 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 60 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=12). Infarction was quantified after a survival period of 24 h. Differences in infarct volume were examined with one-way ANOVA following Dunnet's multiple comparison test. The percentage of cortical infarction in the saline control group was 22.6 +/- 6.8% (mean+/-S.D.) of contra-lateral hemisphere, and in the 30 mg/kg/h NXY-059-treated group was 17.4% +/- 6.8% (NS). Plasma concentration (microM/l) of NXY-059 in the 30 mg/kg/h group was 80.2 +/- 52.2 (n=9), while in the 60 mg/kg/h group plasma concentration (microM/l) of NXY-059 was 391.0 +/- 207.0 (n=10). Infarction in the 60 mg/kg/h NXY-059-treated group was significantly reduced (P=0.009) to 14.5 +/- 5%. Our preliminary data demonstrate that administration of NXY-059 (60 mg/kg/h for 24 h) ameliorates cortical infarction in rats subjected to permanent focal cerebral ischemia with 24 h survival. PMID:11478919

  16. Reduced Hippocampal Dendritic Spine Density and BDNF Expression following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Male Long Evans Rats

    PubMed Central

    Smith, Catherine A.; Holahan, Matthew R.

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats. PMID:25295592

  17. STW 5 (Iberogast ®) reduces afferent sensitivity in the rat small intestine

    Microsoft Academic Search

    M. H. Müller; C.-Y. Liu; J. Glatzle; D. Weiser; O. Kelber; P. Enck; D. Grundy; M. E. Kreis

    2006-01-01

    IntroductionA limited number of drugs are available for the treatment of functional dyspepsia and irritable bowel syndrome. The efficacy of STW 5 (Iberogast®) was previously shown in clinical trials. Since visceral hypersensitivity seems to be the prime pathomechanism of functional gastro-intestinal disorders, the aim of this study was to explore whether STW 5 reduces intestinal afferent sensitivity in the upper

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. An oral dose of calcium montmorillonite clay (i.e. NovaSil, NS) was able to reduce aflatoxin exposure in a Ghanaian population at risk. In vitro...

  19. Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats

    Microsoft Academic Search

    Yu Sun; Rui Yang; Ji-gen Zhong; Feng Fang; Jin-jin Jiang; Ming-yao Liu; Jian Lu

    2009-01-01

    INTRODUCTION: Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. METHODS:

  20. Manganese superoxide dismutase and reduced nicotinamide adenine dinucleotide diaphorase colocalize in the rat gut

    Microsoft Academic Search

    Shengyun Fang; James Christensen

    1995-01-01

    Background & Aims Superoxide and other free radicals participate in inflammatory bowel disease and ischemia-reperfusion injury. Manganese superoxide dismutase (SOD) scavenges superoxide. Mn SOD is colocalized with reduced nicotinamide adenine dinucleotide (NADH) diaphorase in some tissues. NADH diaphorase histochemistry selectively stains enteric nerves. The aim of this study was to seek colocalization of Mn SOD with NADH diaphorase in the

  1. Simvastatin reduces fetal testosterone production and permanently alters reproductive tract development in the male rat

    EPA Science Inventory

    Androgen signaling by fetal Leydig cells is critical in the proper development of the male reproductive tract. As cholesterol is a precursor for hormone biosynthesis,inhibition of the cholesterol pathway during sex differentiation may reduce testosterone {T). We hypothesized tha...

  2. Maize and resistant starch enriched breads reduce postprandial glycemic responses in rats

    Microsoft Academic Search

    Carla M. Brites; Maria J. Trigo; Belmira Carrapiço; Marcela Alviña; Rui J. Bessa

    2011-01-01

    White wheat bread is a poor source of dietary fiber, typically containing less than 2%. A demand exists for the development of breads with starch that is slowly digestible or partially resistant to the digestive process. The utilization of maize flour and resistant starch is expected to reduce the release and absorption of glucose and, hence, lower the glycemic index

  3. Muscarinic cholinergic neuromodulation reduces proactive interference between stored odor memories during associative learning in rats

    Microsoft Academic Search

    Eve De Rosa; Michael E. Hasselmo

    2000-01-01

    Previous electrophysiological studies and computational modeling suggest the hypothesis that cholinergic neuromodulation may reduce olfactory associative interference during learning (M. E. Hasselmo, B. P. Anderson, & J. M. Bower, 1992; M. E. Hasselmo & J. M. Bower, 1993). These results provide behavioral evidence supporting this hypothesis. A simultaneous discrimination task required learning a baseline odor pair (A+B-) and then, under

  4. Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats

    PubMed Central

    Chen, Xiaocong; Sebastian, Becky M.; Tang, Hui; McMullen, Megan M.; Axhemi, Armend; Jacobsen, Donald W.; Nagy, Laura E.

    2009-01-01

    Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular anti-oxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4–7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (C/EBP?, PPAR? and PPAR?) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in C/EBP? and PPAR? normalizing adiponectin mRNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated TNF-? expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation. In conclusion In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, TNF-? expression and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver. PMID:19296466

  5. Lycopene supplementation reduces TNF-? via RAGE in the kidney of obese rats

    PubMed Central

    Pierine, D T; Navarro, M E L; Minatel, I O; Luvizotto, R A M; Nascimento, A F; Ferreira, A L A; Yeum, K-J; Corrêa, C R

    2014-01-01

    Background: The kidney is a target organ for injuries caused by advanced glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is proinflammatory and appears to have a role in the pathogenesis of renal disease due to obesity. Objective: The aim was to verify the effect of obesity on renal damage and the effect of lycopene on these complications Design and Methods: Male Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high-fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene (HD+S+L) for a 6-week period. Results: The HD+S and HD+S+L animals demonstrated insulin resistance (OGTT glucose after 150?min; C: 117.6±3.9

  6. Reduced GABAAR-mediated tonic inhibition in aged rat auditory thalamus

    PubMed Central

    Richardson, Ben D.; Ling, Lynne L.; Uteshev, Victor V.; Caspary, Donald M.

    2013-01-01

    Age-related deficits in detecting and understanding speech, which can lead to social withdrawal and isolation, have been linked to changes in the central auditory system. Many of these central age-related changes involve altered mechanisms of inhibitory neurotransmission, essential for accurate and reliable auditory processing. In sensory thalamus, GABA mediates fast (phasic) inhibition via synaptic GABAAR and long-lasting (tonic) inhibition via high affinity (extrasynaptic) GABAARs which provide a majority of the overall inhibitory tone in sensory thalamus. Due to a delicate balance between excitation and inhibition, alteration of normal thalamic inhibitory function with age and a reduction of tonic GABAAR-mediated inhibition may disrupt normal adult auditory processing, sensory gating, thalamocortical rhythmicity and slow-wave sleep. The present study examined age-related homeostatic plasticity of GABAAR function in auditory thalamus or medial geniculate body (MGB). Using thalamic slices from young adult (3–8 months) and aged (28–32 months) rats, these studies found a 45.5% reduction in GABAAR density and a 50.4% reduction in GABAAR-mediated tonic whole cell Cl? currents in the aged MGB. Synaptic GABAAR-mediated inhibition appeared differentially affected in aged lemniscal and non-lemniscal MGB. Except for resting membrane potential, basic properties were unaltered with age, including neuronal Cl? homeostasis determined using the gramicidin perforated patch-clamp method. Results demonstrate selective significant age-dependent deficits in the tonic inhibitory tone within the MGB. These data suggest that selective GABAAR subtype agonists or modulators might be used to augment MGB inhibitory neurotransmission, improving speech understanding, sensory gating and slow-wave sleep for a subset of elderly individuals. PMID:23325258

  7. Dietary supplementation with a low dose of (-)-epigallocatechin-3-gallate reduces pro-inflammatory responses in peripheral leukocytes of non-obese type 2 diabetic GK rats.

    PubMed

    Uchiyama, Yumiko; Suzuki, Takuji; Mochizuki, Kazuki; Goda, Toshinao

    2013-01-01

    (-)-Epigallocatechin-3-gallate (EGCG), which is largely found in green tea, is known to eliminate reactive oxygen species and associated inflammatory responses in vitro and in cells. However, the in vivo mechanisms underlying the effects of EGCG on the amelioration of metabolic disorders are not fully understood. In this study, we examined whether dietary supplementation with EGCG reduces inflammatory responses in peripheral leukocytes of a non-obese type 2 diabetes animal model, Goto-Kakizaki (GK) rats. GK rats at 9 wk of age were fed a control high-fat diet (46 energy % from lard and corn oil) or a high-fat diet containing 0.1%, 0.2%, or 0.5% EGCG (w/w) for 25 wk. The oxidative stress markers 8-hydroxydeoxyguanosine (OHdG) and total malondialdehyde (MDA) were reduced by supplementation with EGCG at 0.1%, but not at 0.2% or more. Significant reductions in the mRNA levels of genes related to inflammatory responses (TNF-?, IFN-?, IL-1?, IL-6, IL-18, MCP-1, CD11b, and S100a6), 8-OHdG, and total MDA were induced in peripheral leukocytes of GK rats by EGCG supplementation at 0.1%, but not at 0.2% or more, compared with rats fed the control diet. The present results suggest that supplementation with a low dose of EGCG reduces oxidative stress and the expressions of genes involved in inflammation in peripheral leukocytes of GK rats. PMID:24477251

  8. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    PubMed Central

    Ménard, Caroline; Quirion, Rémi; Bouchard, Sylvain; Ferland, Guylaine; Gaudreau, Pierrette

    2014-01-01

    The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6–42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats. PMID:24847259

  9. Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing behavior in rats

    Microsoft Academic Search

    S. Hashimoto; T. Inoue; T. Koyama

    1996-01-01

    Conditioned fear stress (CFS)-induced freezing behavior has been proposed as an animal model of anxiety. In the present study, freezing was used to determine the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs), which are reported to be clinically effective in anxiety disorders. The duration of freezing behavior was reduced by acute treatment with the SSRIs citalopram (1–10 mg\\/kg) and

  10. Pregabalin reduces cocaine self-administration and relapse to cocaine seeking in the rat.

    PubMed

    de Guglielmo, Giordano; Cippitelli, Andrea; Somaini, Lorenzo; Gerra, Gilberto; Li, Hongwu; Stopponi, Serena; Ubaldi, Massimo; Kallupi, Marsida; Ciccocioppo, Roberto

    2013-07-01

    Pregabalin (Lyrica™) is a structural analog of ?-aminobutyric acid (GABA) and is approved by the FDA for partial epilepsy, neuropathic pain and generalized anxiety disorders. Pregabalin also reduces excitatory neurotransmitter release and post-synaptic excitability. Recently, we demonstrated that pregabalin reduced alcohol intake and prevented relapse to the alcohol seeking elicited by stress or environmental stimuli associated with alcohol availability. Here, we sought to extend these findings by examining the effect of pregabalin on cocaine self-administration (0.25?mg/infusion) and on cocaine seeking elicited by both conditioned stimuli and stress, as generated by administration of yohimbine (1.25?mg/kg). The results showed that oral administration of pregabalin (0, 10 or 30?mg/kg) reduced self-administration of cocaine over an extended period (6 hours), whereas it did not modify self-administration of food. In cocaine reinstatement studies, pregabalin (10 and 30?mg/kg) abolished the cocaine seeking elicited by both the pharmacological stressor yohimbine and the cues predictive of cocaine availability. Overall, these results demonstrate that pregabalin may have potential in the treatment of some aspects of cocaine addiction. PMID:22734646

  11. Non-alimentary components in the food-reinforcement of conditioned forelimb-flexion in food-satiated dogs

    Microsoft Academic Search

    W. J. Brogden

    1942-01-01

    The object of this study was to show that the frequency of CR (left forelimb flexion) differs for food-satiated dogs, depending on whether the CR is followed by food (experiment), or is not followed by food (control). As compared with results obtained after 18-20 hours of food-deprivation, the experimental animals showed a decrement of only 7.12% in the frequency of

  12. Green Tea, Phytic Acid, and Inositol in Combination Reduced the Incidence of Azoxymethane-Induced Colon Tumors in Fisher 344 Male Rats

    PubMed Central

    Verghese, Martha; Davis, Shurrita; Williams, Leonard L.

    2011-01-01

    Abstract Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93?M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16?mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO2 euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25±1.23 and 29.83±1.10??mol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent. PMID:21501094

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

    PubMed

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

    2014-07-15

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

  14. Not so fast: speed effects on forelimb kinematics in cercopithecine monkeys and implications for digitigrade postures in primates.

    PubMed

    Patel, Biren A

    2009-09-01

    Terrestrial mammals are characterized by their digitigrade limb postures, which are proposed to increase effective limb length (ELL) to achieve preferred or higher locomotor speeds more efficiently. Accordingly, digitigrade postures are associated with cursorial locomotion. Unlike most medium- to large-sized terrestrial mammals, terrestrial cercopithecine monkeys lack most cursorial adaptations, but still adopt digitigrade hand postures. This study investigates when and why terrestrial cercopithecine monkeys adopt digitigrade hand postures during quadrupedal locomotion. Three cercopithecine species (Papio anubis, Macaca mulatta, Erythrocebus patas) were videotaped moving unrestrained along a horizontal runway at a range of speeds (0.4-3.4 m/s). Three-dimensional forelimb kinematic data were recorded during forelimb support. Hand posture was measured as the angle between the metacarpal segments and the ground (MGA). As predicted, a larger MGA was correlated with a longer ELL. At slower speeds, subjects used digitigrade postures (larger MGA), however, contrary to expectations, all subjects used more palmigrade hand postures (smaller MGA) at faster speeds. Digitigrade postures at slower speeds may lower cost of transport by increasing ELL and step lengths. At higher speeds, palmigrade postures may be better suited to spread out high ground reaction forces across a larger portion of the hand thereby potentially decreasing stresses in hand bones. It is concluded that a digitigrade forelimb posture in primates is not an adaptation for high speed locomotion. Accordingly, digitigrady may have evolved for different reasons in primates compared to other mammalian lineages. PMID:19294733

  15. Inferring the use of forelimb suspensory locomotion by extinct primate species via shape exploration of the ulna.

    PubMed

    Rein, Thomas R; Harvati, Katerina; Harrison, Terry

    2015-01-01

    Uncovering links between skeletal morphology and locomotor behavior is an essential component of paleobiology because it allows researchers to infer the locomotor repertoire of extinct species based on preserved fossils. In this study, we explored ulnar shape in anthropoid primates using 3D geometric morphometrics to discover novel aspects of shape variation that correspond to observed differences in the relative amount of forelimb suspensory locomotion performed by species. The ultimate goal of this research was to construct an accurate predictive model that can be applied to infer the significance of these behaviors. We studied ulnar shape variation in extant species using principal component analysis. Species mainly clustered into phylogenetic groups along the first two principal components. Upon closer examination, the results showed that the position of species within each major clade corresponded closely with the proportion of forelimb suspensory locomotion that they have been observed to perform in nature. We used principal component regression to construct a predictive model for the proportion of these behaviors that would be expected to occur in the locomotor repertoire of anthropoid primates. We then applied this regression analysis to Pliopithecus vindobonensis, a stem catarrhine from the Miocene of central Europe, and found strong evidence that this species was adapted to perform a proportion of forelimb suspensory locomotion similar to that observed in the extant woolly monkey, Lagothrix lagothricha. PMID:25234204

  16. Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

    PubMed Central

    2012-01-01

    Background Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA)-induced monoarthritis (MA). In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. Results Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker) or the glia fibrillary acidic protein (GFAP, an astrocytic marker). These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs) ?2/?-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC ?2/?-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC ?2/?-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p.) gabapentin injections (100?mg/kg, once daily for 4?days with the first injection 60?min before intra-articular CFA) suppressed the activation of spinal microglia, downregulated spinal VGCC ?2/?-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. Conclusions Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia activation induced by joint inflammation. We also show that the VGCC ?2/?-1 subunits might be involved in these events. PMID:22647647

  17. Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

    PubMed Central

    Xiao, DaLiao; Huang, Xiaohui; Xue, Qin; Zhang, Lubo

    2014-01-01

    In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring. PMID:24905716

  18. Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye.

    PubMed

    Katagiri, A; Thompson, R; Rahman, M; Okamoto, K; Bereiter, D A

    2015-04-01

    Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil (MO), a transient receptor potential ankyrin (TRPA1) agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. MO (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of MO (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. MO caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by MO. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE. PMID:25639234

  19. Increased Energy Expenditure Contributes More to the Body Weight-Reducing Effect of Rimonabant than Reduced Food Intake in Candy-Fed Wistar Rats

    Microsoft Academic Search

    Andreas W. Herling; Susanne Kilp; Ralf Elvert; Guido Haschke; Werner Kramer

    2008-01-01

    The CB1 receptor antagonist, rimonabant, affects the endo- cannabinoid system and causes a sustained reduction in body weight (BW) despite the transient nature of the reduction in foodintake.Therefore,inamultiple-dosestudy,femalecandy- fed Wistar rats were treated with rimonabant (10 mg\\/kg) and matched with pair-fed rats to distinguish between hypoph- agic action and hypothesized effects on energy expenditure. Within the first week of treatment,

  20. Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

    PubMed Central

    Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Perriotte-Olson, Curtis; Anders, Krista; Steenson, Sharalyn; Blevins, James E.

    2012-01-01

    Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg?1·h?1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg?1·h?1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. PMID:22510712

  1. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Høydal, MA; Stølen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wisløff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  2. Reduced conduction failure of the main axon of polymodal nociceptive C-fibres contributes to painful diabetic neuropathy in rats.

    PubMed

    Sun, Wei; Miao, Bei; Wang, Xiu-Chao; Duan, Jian-Hong; Wang, Wen-Ting; Kuang, Fang; Xie, Rou-Gang; Xing, Jun-Ling; Xu, Hui; Song, Xue-Jun; Luo, Ceng; Hu, San-Jue

    2012-02-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus and can affect many aspects of life and severely limit patients' daily functions. Signals of painful diabetic neuropathy are believed to originate in the peripheral nervous system. However, its peripheral mechanism of hyperalgesia has remained elusive. Numerous studies have accumulated that polymodal nociceptive C-fibres play a crucial role in the generation and conduction of pain signals and sensitization of which following injury or inflammation leads to marked hyperalgesia. Traditionally, the number of nociceptive primary afferent firings is believed to be determined at the free nerve endings, while the extended main axon of unmyelinated C-fibres only involves the reliable and faithful propagation of firing series to the central terminals. We challenged this classic view by showing that conduction of action potential can fail to occur in response to repetitive activity when they travel down the main axon of polymodal nociceptive C-fibres. Quantitative analysis of conduction failure revealed that the degree of conduction failure displays a frequency-dependent manner. Local administration of low threshold, rapidly activating potassium current blocker, ?-dendrotoxin (0.5?nM) and persistent sodium current blocker, low doses of tetrodotoxin (<100?nM) on the main axon of C-fibres can reciprocally regulate the degree of conduction failure, confirming that conduction failure did occur along the main axon of polymodal nociceptive C-fibres. Following streptozotocin-induced diabetes, a subset of polymodal nociceptive C-fibres exhibited high-firing-frequency to suprathreshold mechanical stimulation, which account for about one-third of the whole population of polymodal nociceptive C-fibres tested. These high-firing-frequency polymodal nociceptive C-fibres in rats with diabetes displayed a marked reduction of conduction failure. Delivery of low concentrations of tetrodotoxin and Nav1.8 selective blocker, A-803467 on the main axon of C-fibres was found to markedly enhance the conduction failure in a dose-dependent manner in diabetic rats. Upregulated expression of sodium channel subunits Nav1.7 and Nav1.8 in both small dorsal root ganglion neurons and peripheral C-fibres as well as enhanced transient and persistent sodium current and increased excitability in small dorsal root ganglion neurons from diabetic rats might underlie the reduced conduction failure in the diabetic high-firing-frequency polymodal nociceptive C-fibres. This study shed new light on the functional capability in the pain signals processing for the main axon of polymodal nociceptive C-fibres and revealed a novel mechanism underlying diabetic hyperalgesia. PMID:22271663

  3. Inactivation Or Inhibition Of Neuronal Activity In The Medial Prefrontal Cortex Largely Reduces Pup Retrieval And Grouping in Maternal Rats

    PubMed Central

    Febo, Marcelo; Felix-Ortiz, Ada C.; Johnson, Tehya R.

    2010-01-01

    Previous research suggests that the maternal medial prefrontal cortex (mPFC) may play a role in maternal care and that cocaine sensitization before pregnancy can affect neuronal activity within this region. The present work was carried out to test whether the mPFC does actually play a role in the expression of maternal behaviors in the rats and to understand what specific behaviors this cortical area may modulate. In the first experiment, tetrodotoxin (TTX) was used to chemically inactivate the mPFC during tests for maternal behavior latencies. Lactating rats were tested on postpartum day 7–9. The results of this first experiment indicate that there is a large effect of TTX-induced inactivation on retrieval behavior latencies. TTX nearly abolished the expression of maternal retrieval of pups without significantly impairing locomotor activity. In the second experiment, GABA-mediated inhibition was used to test maternal behavior latencies and durations of maternal and other behaviors in postpartum dams. In agreement with experiment 1, it was observed that dams capable of retrieving are rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the mPFC largely reduced retrieval without altering other indices of maternal care and non-specific behavior such as ambulation time, self-grooming, and inactivity. Moreover, in both experiments dams were able to establish contact with pups within seconds. The overall results indicate that the mPFC may play an active role in modulating maternal care, particularly retrieval behavior. External factors that affect the function of the frontal cortical site may result in significant impairments in maternal goal-directed behavior as reported in our earlier work. PMID:20156425