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Sample records for rat forelimb reduces

  1. Maladaptive effects of learning with the less-affected forelimb after focal cortical infarcts in rats

    PubMed Central

    Allred, Rachel P.; Jones, Theresa A.

    2009-01-01

    It is common following stroke to focus early rehabilitation efforts on developing compensatory use of the less-affected body side. Here we used a rat model of focal cortical infarct to examine how motor skill acquisition with the less-affected (“intact”) forelimb influences sensorimotor function of the infarct-impaired forelimb and neural activity in peri-infarct cortex. Rats proficient in skilled reaching with one forelimb were given focal ischemic lesions in the contralateral sensorimotor cortex (SMC). Recovery in this forelimb was tested following a period of reach training focused on the intact forelimb or control procedures. Quantitative measures of the cumulatively expressed transcription factor, FosB/ΔFosB, were used to assay intact forelimb training effects on neuronal activity in remaining SMC of the infarcted hemisphere. Intact forelimb training worsened behavioral recovery in the impaired forelimb following unilateral focal ischemia. Furthermore, it decreased neuronal FosB/ΔFosB expression in layer II/III of peri-infarct SMC. These effects were not found in sham-operated rats trained sequentially with both forelimbs or in animals receiving bilateral forelimb training after unilateral infarcts. Thus, focused use of the intact forelimb has detrimental effects on recovery of impaired forelimb function following a focal ischemic injury and this is linked to reduced neuronal activation in remaining cortex. These results suggest that peri-infarct cortex becomes vulnerable to early post-stroke experience with the less-affected forelimb and that this experience may drive neural plasticity here in a direction that is maladaptive for functional outcome. PMID:18054917

  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

    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

  3. 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

  4. Awake behaving electrophysiological correlates of forelimb hyperreflexia, weakness and disrupted muscular synchronization following cervical spinal cord injury in the rat.

    PubMed

    Ganzer, Patrick Daniel; Meyers, Eric Christopher; Sloan, Andrew Michael; Maliakkal, Reshma; Ruiz, Andrea; Kilgard, Michael Paul; Robert, LeMoine Rennaker

    2016-07-01

    Spinal cord injury usually occurs at the level of the cervical spine and results in profound impairment of forelimb function. In this study, we recorded awake behaving intramuscular electromyography (EMG) from the biceps and triceps muscles of the impaired forelimb during volitional and reflexive forelimb movements before and after unilateral cervical spinal cord injury (cSCI) in rats. C5/C6 hemicontusion reduced volitional forelimb strength by more than 50% despite weekly rehabilitation for one month post-injury. Triceps EMG during volitional strength assessment was reduced by more than 60% following injury, indicating reduced descending drive. Biceps EMG during reflexive withdrawal from a thermal stimulus was increased by 500% following injury, indicating flexor withdrawal hyperreflexia. The reduction in volitional forelimb strength was significantly correlated with volitional and reflexive biceps EMG activity. Our results support the hypothesis that biceps hyperreflexia and descending volitional drive both significantly contribute to forelimb strength deficits after cSCI and provide new insight into dynamic muscular dysfunction after cSCI. The use of multiple automated quantitative measures of forelimb dysfunction in the rodent cSCI model will likely aid the search for effective regenerative, pharmacological, and neuroprosthetic treatments for spinal cord injury. PMID:27033345

  5. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.

    PubMed

    Hays, Seth A; Ruiz, Andrea; Bethea, Thelma; Khodaparast, Navid; Carmel, Jason B; Rennaker, Robert L; Kilgard, Michael P

    2016-07-01

    Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID:27255820

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  7. Forelimb Kinematics of Rats Using XROMM, with Implications for Small Eutherians and Their Fossil Relatives

    PubMed Central

    Bonnan, Matthew F.; Shulman, Jason; Varadharajan, Radha; Gilbert, Corey; Wilkes, Mary; Horner, Angela; Brainerd, Elizabeth

    2016-01-01

    The earliest eutherian mammals were small-bodied locomotor generalists with a forelimb morphology that strongly resembles that of extant rats. Understanding the kinematics of the humerus, radius, and ulna of extant rats can inform and constrain hypotheses concerning typical posture and mobility in early eutherian forelimbs. The locomotion of Rattus norvegicus has been extensively studied, but the three-dimensional kinematics of the bones themselves remains under-explored. Here, for the first time, we use markerless XROMM (Scientific Rotoscoping) to explore the three-dimensional long bone movements in Rattus norvegicus during a normal, symmetrical gait (walking). Our data show a basic kinematic profile that agrees with previous studies on rats and other small therians: rats maintain a crouched forelimb posture throughout the step cycle, and the ulna is confined to flexion/extension in a parasagittal plane. However, our three-dimensional data illuminate long-axis rotation (LAR) movements for both the humerus and the radius for the first time. Medial LAR of the humerus throughout stance maintains an adducted elbow with a caudally-facing olecranon process, which in turn maintains a cranially-directed manus orientation (pronation). The radius also shows significant LAR correlated with manus pronation and supination. Moreover, we report that elbow flexion and manus orientation are correlated in R. norvegicus: as the elbow angle becomes more acute, manus supination increases. Our data also suggest that manus pronation and orientation in R. norvegicus rely on a divided system of labor between the ulna and radius. Given that the radius follows the flexion and extension trajectory of the ulna, it must rotate at the elbow (on the capitulum) so that during the stance phase its distal end lies medial to ulna, ensuring that the manus remains pronated while the forelimb is supporting the body. We suggest that forelimb posture and kinematics in Juramaia, Eomaia, and other basal

  8. Forelimb Kinematics of Rats Using XROMM, with Implications for Small Eutherians and Their Fossil Relatives.

    PubMed

    Bonnan, Matthew F; Shulman, Jason; Varadharajan, Radha; Gilbert, Corey; Wilkes, Mary; Horner, Angela; Brainerd, Elizabeth

    2016-01-01

    The earliest eutherian mammals were small-bodied locomotor generalists with a forelimb morphology that strongly resembles that of extant rats. Understanding the kinematics of the humerus, radius, and ulna of extant rats can inform and constrain hypotheses concerning typical posture and mobility in early eutherian forelimbs. The locomotion of Rattus norvegicus has been extensively studied, but the three-dimensional kinematics of the bones themselves remains under-explored. Here, for the first time, we use markerless XROMM (Scientific Rotoscoping) to explore the three-dimensional long bone movements in Rattus norvegicus during a normal, symmetrical gait (walking). Our data show a basic kinematic profile that agrees with previous studies on rats and other small therians: rats maintain a crouched forelimb posture throughout the step cycle, and the ulna is confined to flexion/extension in a parasagittal plane. However, our three-dimensional data illuminate long-axis rotation (LAR) movements for both the humerus and the radius for the first time. Medial LAR of the humerus throughout stance maintains an adducted elbow with a caudally-facing olecranon process, which in turn maintains a cranially-directed manus orientation (pronation). The radius also shows significant LAR correlated with manus pronation and supination. Moreover, we report that elbow flexion and manus orientation are correlated in R. norvegicus: as the elbow angle becomes more acute, manus supination increases. Our data also suggest that manus pronation and orientation in R. norvegicus rely on a divided system of labor between the ulna and radius. Given that the radius follows the flexion and extension trajectory of the ulna, it must rotate at the elbow (on the capitulum) so that during the stance phase its distal end lies medial to ulna, ensuring that the manus remains pronated while the forelimb is supporting the body. We suggest that forelimb posture and kinematics in Juramaia, Eomaia, and other basal

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

    PubMed Central

    Rombola, Angela M.; Rousseau, Celeste A.; Mercier, Lynne M.; Fitzpatrick, Garrett M.; Reier, Paul J.; Fuller, David D.; Lane, Michael A.

    2015-01-01

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

  10. Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

    PubMed

    Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

    2014-12-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding

  11. Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

    PubMed Central

    Alaverdashvili, Mariam; Hackett, Mark J.; Pickering, Ingrid J.; Paterson, Phyllis G.

    2015-01-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The

  12. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

    PubMed Central

    Hasegawa, Atsushi; Takahashi, Masahito; Satomi, Kazuhiko; Ohne, Hideaki; Takeuchi, Takumi; Sato, Shunsuke; Ichimura, Shoichi

    2016-01-01

    The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2 ± 24.7% in juvenile rats and 34.0 ± 19.8% in adult rats. FLS was 60.4 ± 26.8% in juvenile rats and 46.5 ± 26.9% in adult rats. ROM of the elbow and wrist were 88.9 ± 20.6% and 44.4 ± 24.1% in juvenile rats and 70.0 ± 29.2% and 40.0 ± 21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats. PMID:27065569

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

    PubMed

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

    2013-09-01

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

  14. 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

  15. Enhanced function in the good forelimb of hemi-parkinson rats: Compensatory adaptation for contralateral postural instability?

    PubMed Central

    Woodlee, Martin T.; Kane, Jacqueline R.; Chang, Jitsen; Cormack, Lawrence K.; Schallert, Timothy

    2014-01-01

    In this paper we present two new assays of rat motor behavior which can be used to assess function linked to postural stability in each forelimb independently. Postural instability is a major deficit in Parkinson's disease that is resistant to levodopa therapy and contributes to the risk of falling. We applied both tests, one forelimb at a time, to normal rats as well as rats extensively depleted of dopamine by unilateral infusion of 6-hydroxydopamine (6-OHDA, given in the medial forebrain bundle) to produce a hemi-parkinsonian syndrome. The 6-OHDA rats showed severe postural instability in the impaired forelimb, but unexpectedly showed enhanced function in the non-impaired forelimb. The data suggest that the intact hemisphere may undergo rapid reorganization subsequent to unilateral dopamine depletion, which allows for compensatory function of the “intact” limb. Measurements of amphetamine-induced striatal c-fos expression, as well as behavior results gathered when animals were under the influence of apomorphine or haloperidol, indicate that this potential reorganization may require non-dopaminergic neural plasticity. The relevance of these findings for unilateral rat models of neurological disease is discussed. PMID:18417125

  16. Laminar-dependent dendritic spine alterations in the motor cortex of adult rats following callosal transection and forced forelimb use.

    PubMed

    Adkins, DeAnna L; Bury, Scott D; Jones, Theresa A

    2002-07-01

    Previously, the authors found that partial denervation of the motor cortex in adult animals can enhance this region's neuronal growth response to relevant behavioral change. Rats with partial corpus callosum transections that were forced to rely on one forelimb for 18 days had increased dendritic arborization of layer V pyramidal neurons in the opposite motor cortex compared to controls. This was not found as a result of denervation alone or of forced forelimb use alone. However, it seemed possible that each independent manipulation (i.e., forced forelimb use alone and callosal transections alone) resulted in neural structural alterations that were simply not revealed in measurements of dendritic branch number and/or not inclusive of layer V dendrites. This possibility was assessed in the current study with a reexamination of the Golgi-Cox impregnated tissue generated in the previous study. Tissue was quantified from rats that received either partial transections of the rostral two-thirds of the corpus callosum (CCX) or sham operations (Sham) followed either by 18 days of forced use of one forelimb (Use) or unrestricted use of both forelimbs (Cont). Measurements of apical and basilar dendrites from pyramidal neurons of layer II/III and layer V were performed to detect spine addition resulting from either increased spine density or the addition of dendritic material. As hypothesized, significant spine addition was found following forced forelimb use alone (Sham+Use) and callosal transections alone (CCX+Cont). However, forced use primarily increased spines on layer II/III pyramidal neurons, whereas callosal transections primarily increased dendritic spines on layer V pyramidal neurons in comparison to Sham+Cont. A much more robust increase in layer V dendritic spines was found in animals with the combination of forced forelimb use and denervation (CCX+Use). In contrast to the effects of forced use alone, however, CCX+Use rats failed to show major net increases in

  17. 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.

  18. 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

  19. Sensorimotor Experience Influences Recovery of Forelimb Abilities but Not Tissue Loss after Focal Cortical Compression in Adult Rats

    PubMed Central

    Martinez, Marina; Brezun, Jean-Michel; Xerri, Christian

    2011-01-01

    Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5–C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury. PMID:21359230

  20. Large-scale cortical reorganization following forelimb deafferentation in rat does not involve plasticity of intracortical connections.

    PubMed

    Pearson, P P; Arnold, P B; Oladehin, A; Li, C X; Waters, R S

    2001-05-01

    Physiological mapping of the body representation 1 month or longer after forelimb removal in adult rats revealed new pockets of shoulder representation in the forepaw barrel subfield (FBS) in the first somatosensory cortex (SI). These "new" shoulder representations have longer evoked response latencies than sites in the shoulder representation within the trunk subfield, hereafter referred to as the "original" shoulder representation. We postulated that the "new" shoulder representations in the FBS were relayed from the "original" shoulder representation. We investigated this hypothesis by studying anatomical connectivity between the "original" shoulder representation and the FBS in intact control and forelimb deafferented adult rats using Phaseolus vulgaris leucoagglutinin (PHA-L), biocytin, and biotin dextran-amine (BDA) as anterograde tracers. The retrograde tracer cholera toxin beta subunit (CT-B) injected into the FBS was also used to study connectivity between the "original" shoulder representation and the FBS. Using these anatomical tracing techniques, we were unable to show the existence of a direct corticocortical connection between the "original" shoulder representation in the trunk subfield and the FBS in either intact or deafferented rats. Functional connectivity between the two cortical regions was studied by ablating the "original" shoulder representation alone or in combination with the shoulder representation in the second somatosensory cortex (SII) while recording evoked responses in the FBS following electrical stimulation of the shoulder. Both ablations failed to eliminate the evoked responses at the "new" shoulder sites in the FBS, suggesting that SI and SII are not necessary for "new" shoulder input in the FBS. It is suggested that subcortical sites may play a major role in large-scale cortical reorganization. Results of projections from the "original" shoulder representation to parietal medial (PM), parietal lateral (PL), SII, parietal ventral

  1. Complex movement topography and extrinsic space representation in the rat forelimb motor cortex as defined by long-duration intracortical microstimulation.

    PubMed

    Bonazzi, Laura; Viaro, Riccardo; Lodi, Enrico; Canto, Rosario; Bonifazzi, Claudio; Franchi, Gianfranco

    2013-01-30

    Electrical stimulation of the motor cortex in the rat can evoke complex forelimb multi-joint movements, including movement of limb and paw. In this study, these movements have been quantified in terms of 3D displacement and kinematic variables of two markers positioned on the wrist and middle digits (limb and paw movement, respectively). Electrical microstimulation was applied to the motor cortex using a pulse train of 500 ms duration. Movements were measured using a high-resolution 3D optical system. Five classes of limb movements (abduction, adduction, extension, retraction, elevation) and four classes of paw movements (opening, closure, opening/closure sequence, supination) were described according to their kinematics. A consistent topography of these classes of movements was presented across the motor cortex together with a topography of spatial locations to which the paw was directed. In about one-half of cortical sites, a specific pattern of limb-paw movement combination did exist. Four categories of limb-paw movements resembling behavioral repertoire were identified: reach-shaping, reach-grasp sequence, bring-to-body, and hold-like movement. Overall, the forelimb motor region included: (1) a large caudal forelimb area dominated by reach-shaping movement representation; (2) a small rostral area containing reach-grasp sequence and bring-to-body movement representation; and (3) a more lateral portion where hold-like movement was represented. These results support the view that, in rats, the motor cortex controls forelimb movements at a relatively complex level and suggest that the orderly representation of complex movements and their dynamics/kinematics emerge from the principles of forelimb motor cortex organization. PMID:23365246

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

    PubMed Central

    2012-01-01

    Background A complete spinal cord transection results in loss of all supraspinal motor control below the level of the injury. The neural circuitry in the lumbosacral spinal cord, however, can generate locomotor patterns in the hindlimbs of rats and cats with the aid of motor training, epidural stimulation and/or administration of monoaminergic agonists. We hypothesized that there are patterns of EMG signals from the forelimbs during quadrupedal locomotion that uniquely represent a signal for the “intent” to step with the hindlimbs. These observations led us to determine whether this type of “indirect” volitional control of stepping can be achieved after a complete spinal cord injury. The objective of this study was to develop an electronic bridge across the lesion of the spinal cord to facilitate hindlimb stepping after a complete mid-thoracic spinal cord injury in adult rats. Methods We developed an electronic spinal bridge that can detect specific patterns of EMG activity from the forelimb muscles to initiate electrical-enabling motor control (eEmc) of the lumbosacral spinal cord to enable quadrupedal stepping after a complete spinal cord transection in rats. A moving window detection algorithm was implemented in a small microprocessor to detect biceps brachii EMG activity bilaterally that then was used to initiate and terminate epidural stimulation in the lumbosacral spinal cord. We found dominant frequencies of 180–220 Hz in the EMG of the forelimb muscles during active periods, whereas these frequencies were between 0–10 Hz when the muscles were inactive. Results and conclusions Once the algorithm was validated to represent kinematically appropriate quadrupedal stepping, we observed that the algorithm could reliably detect, initiate, and facilitate stepping under different pharmacological conditions and at various treadmill speeds. PMID:22691460

  3. 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

  4. Restoration of complex sensorimotor behavior and skilled forelimb use by a modified nigral cell suspension transplantation approach in the rat Parkinson model.

    PubMed

    Nikkhah, G; Duan, W M; Knappe, U; Jödicke, A; Björklund, A

    1993-09-01

    While intrastriatal transplants of dopamine-rich ventral mesencephalic tissue are effective in reversing a variety of drug-induced behaviors in the rat Parkinson model, previous studies have failed to obtain significant graft-induced effects on deficits in certain aspects of complex sensorimotor behaviors. In the present study we have applied a modified cell suspension transplantation procedure, which allows more reproducible and consistent ventral mesencephalic transplants of large size, as well as more wide-spread distribution of the ventral mesencephalic tissue over multiple graft sites within the denervated caudate-putamen. Using this approach it has for the first time been possible to obtain significant amelioration of the lesion-induced deficits in skilled forelimb use and in the rats ability to switch from one behavior (eating) to another (orientation towards tactile stimuli), so-called disengage behavior. Rats with unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine pathway received a total of 450,000 fetal ventral mesencephalic cells, implanted either as two large deposits along a single injection tract ("Macro" grafts), or as 18 small deposits along six injection tracts in the head of the denervated caudate-putamen ("Micro" grafts) and the behavioral changes were studied up to three months after transplantation. On the drug-induced tests, both types of transplants reversed amphetamine- and D1-receptor agonist-induced turning, and produced a partial (50-75%) reduction in apomorphine-induced and D2-receptor agonist-induced turning. On the spontaneous sensorimotor tests, both types of grafts reversed the deficit in simple sensorimotor orientation. In addition, the Micro-grafted animals (which produced the most extensive reinnervation of the denervated striatum) showed a significant improvement in skilled forelimb use and in response latency in the disengage behavior test. Although the large sized Macro-grafted animals showed a similar trend, it

  5. Voluntary exercise reduces the neurotoxic effects of 6-hydroxydopamine in maternally separated rats

    PubMed Central

    Mabandla, Musa Vuyisile; Russell, Vivienne Ann

    2010-01-01

    Maternal separation has been associated with development of anxiety-like behaviour and learning impairments in adult rats. This has been linked to changes in brain morphology observed after exposure to high levels of circulating glucocorticoids during the stress-hyporesponsive period (P4 to P14). In the present study, adult rats that had been subjected to maternal separation (180 min/day for 14 days) during the stress-hyporesponsive period, received unilateral infusions of a small dose of 6-hydroxydopamine (6-OHDA, 5 μg/4 μl saline) into the medial forebrain bundle. The results showed that voluntary exercise had a neuroprotective effect in both non-stressed and maternally separated rats in that there was a decrease in forelimb akinesia (step test) and limb use asymmetry (cylinder test). Maternal separation increased forelimb akinesia and forelimb use asymmetry and reduced the beneficial effect of exercise on forelimb akinesia. It also reduced exploratory behaviour, consistent with anxiety-like behaviour normally associated with maternal separation. Exercise appeared to reduce dopamine neuron destruction in the lesioned substantia nigra when expressed as a percentage of the non-lesioned hemisphere. However, this appeared to be due to a compensatory decrease in completely stained tyrosine hydroxylase positive neurons in the contralateral, non-lesioned substantia nigra. In agreement with reports that maternal separation increases the 6-OHDA-induced loss of dopamine terminals in the striatum, there was a small increase in dopamine neuron destruction when expressed as a percentage of the non-lesioned hemisphere but there was no difference in dopamine cell number, suggesting that exposure to maternal separation did not exacerbate dopamine cell loss. PMID:20206210

  6. 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

  7. 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

  8. Forelimb training drives transient map reorganization in ipsilateral motor cortex.

    PubMed

    Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

    2016-10-15

    Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. PMID:27392641

  9. Cineradiographic (video X-ray) analysis of skilled reaching in a single pellet reaching task provides insight into relative contribution of body, head, oral, and forelimb movement in rats.

    PubMed

    Alaverdashvili, Mariam; Leblond, Hugues; Rossignol, Serge; Whishaw, Ian Q

    2008-10-10

    The forelimb movements (skilled reaching) used by rats to reach for a single food pellet to place into the mouth have been used to model many neurological conditions. They have been described as a sequence of oppositions of head-pellet, paw-pellet and pellet-mouth that can be described as movements of the distal portion of body segments in relation to their fixed proximal joints. Movement scoring is difficult, however, because the location and movement of body segments is estimated through the overlying fur and skin, which is pliable and partially obscures movement. Using moderately high-speed cineradiographic filming from lateral, dorsal, and frontal perspectives, the present study describes how forelimb and skeletal bones move during the skilled reaching act. The analysis indicates that: (i) head movements for orienting to food, enabled by the vertical orientation of the rostral spinal cord, are mainly independent of trunk movement, (ii) skilled reaching consists of a sequence of upper arm and extremity movements each involving a number of concurrent limb segment and joint movements and (iii) food pellets are retrieved from the paw using either the incisors and/or tongue. The findings are discussed in relation to the idea that X-ray cinematography is valuable tool for assisting descriptive analysis and can contribute to understanding general principles of the relations between whole body, head, oral, and upper extremity movement. PMID:18514337

  10. Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke.

    PubMed

    Starkey, Michelle Louise; Bleul, Christiane; Zörner, Björn; Lindau, Nicolas Thomas; Mueggler, Thomas; Rudin, Markus; Schwab, Martin Ernst

    2012-11-01

    Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the

  11. 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.

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

    PubMed

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

    2013-12-01

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

  13. Phylogeny and forelimb disparity in waterbirds.

    PubMed

    Wang, Xia; Clarke, Julia A

    2014-10-01

    Previous work has shown that the relative proportions of wing components (i.e., humerus, ulna, carpometacarpus) in birds are related to function and ecology, but these have rarely been investigated in a phylogenetic context. Waterbirds including "Pelecaniformes," Ciconiiformes, Procellariiformes, Sphenisciformes, and Gaviiformes form a highly supported clade and developed a great diversity of wing forms and foraging ecologies. In this study, forelimb disparity in the waterbird clade was assessed in a phylogenetic context. Phylogenetic signal was assessed via Pagel's lambda, Blomberg's K, and permutation tests. We find that different waterbird clades are clearly separated based on forelimb component proportions, which are significantly correlated with phylogeny but not with flight style. Most of the traditional contents of "Pelecaniformes" (e.g., pelicans, cormorants, and boobies) cluster with Ciconiiformes (herons and storks) and occupy a reduced morphospace. These taxa are closely related phylogenetically but exhibit a wide range of ecologies and flight styles. Procellariiformes (e.g., petrels, albatross, and shearwaters) occupy a wide range of morphospace, characterized primarily by variation in the relative length of carpometacarpus and ulna. Gaviiformes (loons) surprisingly occupy a wing morphospace closest to diving petrels and penguins. Whether this result may reflect wing proportions plesiomorphic for the waterbird clade or a functional signal is unclear. A Bayesian approach detecting significant rate shifts across phylogeny recovered two such shifts. At the base of the two sister clades Sphenisciformes + Procellariiformes, a shift to an increase evolutionary rate of change is inferred for the ulna and carpometacarpus. Thus, changes in wing shape begin prior to the loss of flight in the wing-propelled diving clade. Several shifts to slower rate of change are recovered within stem penguins. PMID:24989899

  14. Forelimb muscle activity during equine locomotion.

    PubMed

    Harrison, Simon M; Whitton, R Chris; King, Melissa; Haussler, Kevin K; Kawcak, Chris E; Stover, Susan M; Pandy, Marcus G

    2012-09-01

    Few quantitative data exist to describe the activity of the distal muscles of the equine forelimb during locomotion, and there is an incomplete understanding of the functional roles of the majority of the forelimb muscles. Based on morphology alone it would appear that the larger proximal muscles perform the majority of work in the forelimb, whereas the smaller distal muscles fulfil supplementary roles such as stabilizing the joints and positioning the limb for impact with the ground. We measured the timing and amplitude of the electromyographic activity of the intrinsic muscles of the forelimb in relation to the phase of gait (stance versus swing) and the torque demand placed on each joint during walking, trotting and cantering. We found that all forelimb muscles, except the extensor carpi radialis (ECR), were activated just prior to hoof-strike and deactivated during stance. Only the ECR was activated during swing. The amplitudes of muscle activation typically increased as gait speed increased. However, the amplitudes of muscle activation were not proportional to the net joint torques, indicating that passive structures may also contribute significantly to torque generation. Our results suggest that the smaller distal muscles help to stabilize the forelimb in early stance, in preparation for the passive structures (tendons and ligaments) to be stretched. The distal forelimb muscles remain active throughout stance only during canter, when the net torques acting about the distal forelimb joints are highest. The larger proximal muscles activate in a complex coordination to position and stabilize the shoulder and elbow joints during ground contact. PMID:22875767

  15. Experimental Forelimb Allotransplantation in Canine Model.

    PubMed

    Hong, Sa-Hyeok; Eun, Seok-Chan

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  16. Experimental Forelimb Allotransplantation in Canine Model

    PubMed Central

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  17. 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 (α-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

  18. Forelimb lameness in the young patient.

    PubMed

    Cook, J L

    2001-01-01

    Forelimb lameness is a common problem in young dogs and can be caused by a wide variety of problems. Accurate and comprehensive diagnosis and treatment must be provided for these patients. Differential diagnoses for forelimb lameness in the young patient fall into the categories of congenital abnormalities; developmental disorders; trauma; and infectious, nutritional, metabolic, and neoplastic causes. The etiopathogeneses of many of these disorders are still unknown, and treatment options and prognoses vary tremendously. Until definitive causes are determined, it is the responsibility of veterinarians to address the factors that contribute to the development and progression of these disorders. These areas primarily involve weight and nutritional management as well as breeding programs. PMID:11787264

  19. 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...

  20. Viewing a forelimb induces widespread cortical activations.

    PubMed

    Raos, Vassilis; Kilintari, Marina; Savaki, Helen E

    2014-04-01

    Given that prerequisite of activating the mirror neuron system is the preshaping of the hand and its interaction with the object during observation of a reaching-to-grasp-an-object action, the effects of viewing the object, the reaching forelimb and the static hand may obscure the effects of observing the grasping action per se. To disentangle these effects, we employed the (14)C-deoxyglucose quantitative autoradiographic method to map the functional activity in the entire cortex of monkeys (Macaca mulatta) which observed the experimenter performing non-goal-directed (purposeless) forelimb movements towards an object that was previously presented but no longer visible. Thus, our monkeys were exposed to the view of an object, a moving arm and a static hand with extended wrist and fingers. The distribution of metabolic activity was analyzed in 20μm thick brain sections, and two dimensional maps were reconstructed in the occipital operculum, the temporal, the lateral and medial parietal, the lateral and medial frontal, the lateral prefrontal and orbitofrontal cortices, including the cortex within the lunate, superior temporal, lateral, parietoccipital, intraparietal, central, arcuate and principal sulci. Increased metabolic activity, as compared to fixation-control monkeys, was measured in the forelimb representation of the primary motor and somatosensory cortices, the premotor cortices F2 and F5, cingulate motor areas, the secondary somatosensory cortex SII, the posterior intraparietal area 5 and areas TPOc and FST, in the hemisphere contralateral to the moving arm. Moreover, bilateral activations were elicited in areas pre-SMA, 8m, SSA and the somatorecipient area VS, the retroinsula, the auditory belt area CM, motion areas MT, MST, LOP/CIP, area 31, visual areas TEO, V6, V6Av and the parafoveal and peripheral visual representations of areas V1 and V2, respectively. Few parietal, auditory and visual areas were bilaterally depressed. In brief, a surprisingly wide

  1. Essential oil compounds as stress reducing agents in rats.

    PubMed

    Kaewwongse, M; Sanesuwan, K; Pupa, P; Bullangpoti, V

    2013-01-01

    Essential oil compounds were studied to demonstrate their potential as stress reducing agents against rats. Rats were intraperitoneal administered with Linalool, Cineole and Thymol, respectively. Anxiety-related behaviors were determined by open field test and elevated plus maze test. Thymol reduced anxiety-related behavior of the animals. Linalool had no effect in both sexes of rats in the open field test. Thus, the results suggested that Thymol and Linalool are safe to control pets without harming non-target mammals PMID:25145237

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

    PubMed Central

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

    2012-01-01

    Summary The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development. PMID:23213437

  3. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

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

  4. Reduced exposure to microwave radiation by rats: frequency specific effects

    SciTech Connect

    D'Andrea, J.A.; DeWitt, J.R.; Portuguez, L.M.; Gandhi, O.P.

    1988-01-01

    Previous research has shown that SAR hotspots are induced within the laboratory rat and that the resulting thermal hotspots are not entirely dissipated by bloodflow. Two experiments were conducted to determine if hotspot formation in the body and tail of the rat, which is radiation frequency specific, would have behavioral consequences. In the first experiment rats were placed in a plexiglas cage one side of which, when occupied by the rat, commenced microwave radiation exposure; occupancy of the other side terminated exposure. Groups of rats were tested during a baseline period to determine the naturally preferred side of the cage. Subsequent exposure to 360-MHz, 700-MHz or 2450-MHz microwave radiation was made contingent on preferred-side occupancy. A significant reduction in occupancy of the preferred side of the cage, and hence, microwaves subsequently occurred. Reduced exposure to 360-MHz and 2450-MHz microwaves at 1, 2, 6 and 10 W/kg were significantly different from 700-MHz microwaves. In the second experiment semichronic exposures revealed the threshold for reduced exposure of 2450-MHz microwaves to be located between whole-body SAR's of 2.1 and 2.8 W/kg.

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

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

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

  6. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

    PubMed

    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation. PMID:26138461

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

    PubMed

    Kao, Tina; Shumsky, Jed S; Murray, Marion; Moxon, Karen A

    2009-06-10

    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/d, 5 d/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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  10. Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

    PubMed Central

    Bordia, Tanuja; McIntosh, J. Michael

    2012-01-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use. PMID:22144565

  11. The comparative anatomy of the forelimb veins of primates.

    PubMed Central

    Thiranagama, R; Chamberlain, A T; Wood, B A

    1989-01-01

    One hundred and thirteen forelimbs taken from 62 individuals belonging to 17 primate genera were dissected to reveal the entire course of the superficial venous system. The course of the deep venous system was also documented in at least one forelimb of each primate genus, and the number and location of perforating veins was recorded in 18 human and 45 non-human primate limbs. In Pan, Gorilla and in about 25% of human specimens the lateral superficial vein was confined to the forearm, while in all other primates, and in the majority of humans, this vein extended from the carpus to the clavicular region. Only Pongo and humans exhibited a second main superficial vein on the medial side of the forearm. In all primates the deep veins of the forelimb usually accompanied the arteries. Thus variation in the deep venous system reflected the different arterial patterns exhibited by these primates. The number of perforating veins in the forelimb was related to the length of the limb. Primate genera with longer forelimbs had more perforators, though not as many as would be expected if the number of perforators scaled linearly with limb length. PMID:2514175

  12. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

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

    2009-01-01

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

  13. 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

  14. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

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

    2015-01-01

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

  15. Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes.

    PubMed

    Liu, Zheng; Zhang, Li-Ping; Ma, Hui-Jie; Wang, Chuan; Li, Ming; Wang, Qing-Shan

    2005-10-25

    Resveratrol (trans-3, 4', 5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity. The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentration ([Ca(2+)](i)) in rat ventricular myocytes. [Ca(2+)](i) was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 mumol/L) reduced [Ca(2+)](i) in normal and Ca(2+)-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca(2+)](i) in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644 (10 mumol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca(2+)](i) increase in Ca(2+)-free Tyrode's solution (P<0.01). When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, resveratrol (60 mumol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca(2+)](i). These results suggest that resveratrol may reduce the [Ca(2+)](i) in isolated rat ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel and tyrosine kinase, and alleviation of Ca(2+) release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease. PMID:16220198

  16. Parkinson's disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.

    PubMed

    Zhu, Hongyan; Wang, Ziyi; Jin, Jiahui; Pei, Xiao; Zhao, Yuxiao; Wu, Hao; Lin, Weide; Tao, Jie; Ji, Yonghua

    2016-07-15

    Parkinson's disease (PD) is a neurodegenerative disorder and characterized by motor disabilities which are mostly linked with high levels of synchronous oscillations in the basal ganglia neurons. Voltage-gated sodium channels (VGSCs) play a vital role in the abnormal electrical activity of neurons in the globus pallidus (GP) and the subthalamic nucleus (STN) in PD. BmK I, a α-like toxin purified from the Chinese scorpion Buthus martensi Karsch, has been identified a site-3-specific modulator of VGSCs. The present study shows that forelimb akinesia can be induced by the injection of BmK I into the globus pallidus (GP) in rats. In addition, BmK I cannot produce neuronal damage in vivo and in vitro at 24h after treatment, indicating that the forelimb akinesia does not result from neuronal damage. Electrophysiological studies further revealed that the inactivated Na(+) currents were showed to be more vulnerably modulated by BmK I than the activated Na(+) currents in human neuron-like SHSY5Y cells. Furthermore, the modulation of BmK I on inactivation was preferentially attributed to fast inactivation rather than slow inactivation. Therefore, the PD-like forelimb akinesia may result from the modulation of sodium channels in neuron by BmK I. These findings not only suggest that BmK I may be an effective and novel molecule for the study of pathogenesis in PD but also support the idea that VGSCs play a crucial role in the motor disabilities in PD. PMID:27108049

  17. Noribogaine reduces nicotine self-administration in rats.

    PubMed

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

    2015-06-01

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

  18. Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

    PubMed Central

    XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

    2016-01-01

    The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

  19. Dimensions of forelimb muscles in orangutans and chimpanzees

    PubMed Central

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

    2009-01-01

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

  20. SKELETAL MORPHOLOGY OF THE FORELIMB OF MYRMECOPHAGA TRIDACTYLA.

    PubMed

    Sesoko, Natália Ferreira; Rahal, Sheila Canevese; Bortolini, Zara; de Souza, Lívia Pasini; Vulcano, Luiz Carlos; Monteiro, Frederico Ozanan Barros; Teixeira, Carlos Roberto

    2015-12-01

    Anteater forelimbs are morphologically adapted to obtain food and to provide defense and locomotion. Four species are known, but there are few anatomical studies presenting the morphologic features of each species. The aim of this study was to describe the skeletal morphology of the giant anteater (Myrmecophaga tridactyla) forelimb. Pictures and schematic drawings of six cadavers were created to show the bone morphology. In addition, radiographs and computed tomographs were obtained. The skeletal structure of the forelimb had several notable anatomical features. The scapula had two spines, with apparent differences between infant and adult animals. The humerus had a pectoral ridge, a pectoral tubercle, and a pronounced medial epicondyle that represent the origins of muscles important for fossorial activity. The radius had cranial, lateral, and caudal ridges that became more prominent in older animals, and the distal condyle joint provided enhanced support of the dorsal articulation for the manus. Knowledge of the bone morphology of the forelimb generates a better understanding of giant anteater habits and helps in the diagnosis of skeletal abnormalities and in the routine medical assessment of this species. PMID:26667527

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

    PubMed

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

    2011-01-01

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

  2. Naturally-occurring forelimb lameness in the horse results in significant compensatory load redistribution during trotting.

    PubMed

    Maliye, Sylvia; Voute, Lance C; Marshall, John F

    2015-05-01

    This study aimed to quantify the compensatory response to naturally-occurring forelimb lameness on load redistribution. Data from lameness investigations using an inertial sensor based system to monitor the response to forelimb diagnostic anaesthesia were reviewed. Horses with primary forelimb lameness were grouped for analysis as (1) all horses combined (n= 28), (2) forelimb-only lameness (n= 8/28), (3) forelimb-contralateral hindlimb lameness (n= 14/28), (4) forelimb-ipsilateral hindlimb lameness (n= 6/28). The effect of diagnostic anaesthesia on measures of head and pelvic movement asymmetry was determined using the Wilcoxon signed rank test. Spearman's correlation analysis was performed between forelimb and hindlimb variables. Statistical significance was set at P< 0.05. Forelimb diagnostic anaesthesia resulted in a decrease in pelvic movement asymmetry among all horses and the forelimb-only and forelimb-contralateral hindlimb lameness groups. Pelvic movement asymmetry associated with the contralateral hindlimb decreased by a median of 38% (interquartile range [IQR] 10-65%), 43% (IQR 28-60%) and 28% (IQR 12-67%) in all horses, forelimb-only and forelimb-contralateral hindlimb groups respectively (P< 0.05). Maximum pelvic height difference (PDMax) significantly decreased in all horses combined and the forelimb-contralateral hindlimb lameness group by a median of 66% (IQR 24-100%) and 78% (IQR 27-100%, P< 0.01), respectively. Change in head movement asymmetry and vector sum was significantly positively correlated with PDMax in all horses combined and the forelimb-contralateral hindlimb group (P< 0.05). Forelimb lameness had a significant effect on hindlimb and pelvic movement in horses with clinical lameness resulting in compensatory load redistribution and decreased push-off from the contralateral hindlimb. PMID:25862395

  3. Pyramidal tract neurons receptive to different forelimb joints act differently during locomotion

    PubMed Central

    Stout, Erik E.

    2012-01-01

    During locomotion, motor cortical neurons projecting to the pyramidal tract (PTNs) discharge in close relation to strides. How their discharges vary based on the part of the body they influence is not well understood. We addressed this question with regard to joints of the forelimb in the cat. During simple and ladder locomotion, we compared the activity of four groups of PTNs with somatosensory receptive fields involving different forelimb joints: 1) 45 PTNs receptive to movements of shoulder, 2) 30 PTNs receptive to movements of elbow, 3) 40 PTNs receptive to movements of wrist, and 4) 30 nonresponsive PTNs. In the motor cortex, a relationship exists between the location of the source of afferent input and the target for motor output. On the basis of this relationship, we inferred the forelimb joint that a PTN influences from its somatosensory receptive field. We found that different PTNs tended to discharge differently during locomotion. During simple locomotion shoulder-related PTNs were most active during late stance/early swing, and upon transition from simple to ladder locomotion they often increased activity and stride-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically did not change activity, modulation, or discharge duration on the ladder. Wrist-related PTNs were most active during swing and upon transition to the ladder often decreased activity and increased modulation while reducing discharge duration. These data suggest that during locomotion the motor cortex uses distinct mechanisms to control the shoulder, elbow, and wrist. PMID:22236716

  4. Reduced intravenous toxicity of amiodarone nanosuspension in mice and rats.

    PubMed

    Barle, Ester Lovšin; Cerne, Manica; Peternel, Luka; Homar, Miha

    2013-07-01

    The toxicity of amiodarone Lek formulation (test formulation) was investigated after a single intravenous (i.v.) administration to mice and rats. When compared to the reference item, Cordarone (Cordarone(®); Wyeth Pharmaceuticals Inc., Collegeville, Pennsylvania, USA), median lethal dose (LD(50)) after i.v. administration in female mice was 294.0 mg/kg body weight (b.w.) for the test formulation and 227.5 mg/kg b.w. for Cordarone. In female rats after i.v. administration, the LD(50) value was 269.9 mg/kg b.w. for the test formulation and 192.4 mg/kg b.w. for Cordarone. By altering the particle size of amiodarone in the Lek formulation, we were able to improve the solubility of amiodarone, thereby decreasing the number and quantity of excipients needed for preparation of the i.v. formulation and, consequently, reduced the acute toxic effects observed in the present study. PMID:22950665

  5. Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage.

    PubMed

    Lekic, Tim; Flores, Jerry; Klebe, Damon; Doycheva, Desislava; Rolland, William B; Tang, Jiping; Zhang, John H

    2016-01-01

    Germinal matrix hemorrhage (GMH) is the most devastating neurological problem of premature infants. Current treatment strategies are ineffective and brain injury is unpreventable. Insulin-like growth factor 1 (IGF-1) is an endogenous protein shown to have multiple neuroprotective properties. We therefore hypothesized that IGF-1 would reduce brain injury after GMH. Neonatal rats (P7 age) received stereotactic collagenase into the right ganglionic eminence. The following groups were studied: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal IGF-1. Three days later, the animals were evaluated using the righting-reflex (early neurobehavior), Evans blue dye leakage (blood-brain barrier (BBB) permeability), brain water content (edema), and hemoglobin assay (extent of bleeding). Three weeks later, juvenile rats were tested using a water maze (delayed neurobehavior), and then were sacrificed on day 28 for assessment of hydrocephalus (ventricular size). Intranasal IGF-1 treated animals had improved neurological function, and amelioration of BBB permeability, edema, and re-bleeding. IGF-1 may play a part in protective brain signaling following GMH, and our observed protective effect may offer new promise for treatment targeting this vulnerable patient population. PMID:26463950

  6. Noribogaine reduces nicotine self-administration in rats

    PubMed Central

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

    2015-01-01

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

  7. The timing and amount of vagus nerve stimulation during rehabilitative training affect post-stroke recovery of forelimb strength

    PubMed Central

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

    2014-01-01

    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 demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training substantially improves recovery of forelimb strength compared to 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 two hours after daily rehabilitative training sessions resulted in significantly less improvement compared to 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 to 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 post-stroke and indicate that both the timing and amount of VNS should be optimized to maximize therapeutic benefits. PMID:24818637

  8. 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

  9. Statins Reduce the Risks of Relapse to Addiction in Rats.

    PubMed

    Chauvet, Claudia; Nicolas, Celine; Lafay-Chebassier, Claire; Jaber, Mohamed; Thiriet, Nathalie; Solinas, Marcello

    2016-05-01

    Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks. PMID:26466819

  10. Stepping test in mice: a reliable approach in determining forelimb akinesia in MPTP-induced Parkinsonism.

    PubMed

    Blume, Shannon R; Cass, Daryn K; Tseng, Kuei Y

    2009-09-01

    Currently existing behavioral measures for motor impairments in rodent models with bilateral dopamine depletion have demonstrated to be difficult to assess due to the degree of task complexity. There is clearly a need for a behavioral test that is simplistic in design and does not require the animal to learn a specific task, in particular for mice. Here we adapted the stepping test, originally designed for assessing asymmetric motor deficits in rats (Olsson, M., Nikkhah, G., Bentlage, C., Bjorklund, A., 1995. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J. Neurosci. 15, 3863-3875; Schallert, T., De Ryck, M., Whishaw, I.Q., Ramirez, V.D., Teitelbaum, P., 1979. Excessive bracing reactions and their control by atropine and l-DOPA in an animal analog of Parkinsonism. Exp. Neurol. 64, 33-43), into a mouse-friendly version for bilateral dopamine lesion induced by subacute MPTP injection. We found that MPTP-treated mice exhibit a significant and persistent reduction in the number of adjusting steps when compared to saline-treated animals. Typically, MPTP-induced stepping deficit becomes apparent by the fourth MPTP injection. The number of adjusting steps continues to decline throughout the injections, and by day 10 from the last MPTP injection, the stepping deficit observed is associated with approximately 65% TH positive cells loss in the SN. Importantly, L-DOPA administration significantly improved stepping performance in MPTP-treated mice. Thus, stepping test in mice is a reliable and simple behavioral measure for assessing forelimb akinesia induced by systemic MPTP. PMID:19460369

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

    PubMed

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

    2009-10-31

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

  12. Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

    PubMed

    Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

    2016-04-01

    It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. PMID:26826333

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

    PubMed Central

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

    2015-01-01

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

  14. 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 β-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacupuncture, or both, at Baihui (GV20) and Shenshu (BL23). Axin expression was lower, β-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 β-catenin expression in the Wnt signal transduction pathway. PMID:25206919

  15. Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats.

    PubMed

    Reeves, Philip G; Demars, Lana C S; Johnson, W Thomas; Lukaski, Henry C

    2005-01-01

    The mechanism for reduced Fe absorption in Cu deficiency is unknown, but may involve the intestinal Cu-dependent ferroxidase, Hephaestin (Hp). A 2 x 2 factorial experiment was designed to include Cu-deficient (CuD) and Cu-adequate (CuA) male and female rats. Weanling rats of both sexes were randomly divided into 2 groups each and fed an AIN-93G diet with low (<0.3 mg/kg; CuD) or adequate Cu (5.0 mg/kg; CuA). After 19 d, rats were fed 1.0 g each of their respective diets labeled with (59)Fe. Retained (59)Fe was monitored by whole-body counting for 12 d. Then, rats were killed for (59)Fe and Fe measurements in blood and various organs. Duodenal enterocytes were isolated for Western blot analysis of Hp. Signs of Cu and Fe deficiency were evident in both sexes. CuD male rats absorbed 60% as much Fe as CuA male rats (P < 0.001), whereas CuD female rats absorbed 70% (P < 0.001) as much as CuA females, with no difference between the sexes. Hp protein in enterocytes of CuD rats of both sexes was only 35% of that in CuA rats. The biological half-life of (59)Fe in CuD rats was only 50% (P < 0.001) of that in CuA rats, suggesting that Fe turnover was faster in CuD rats than CuA rats. Serum, spleen, and kidney Fe were lower (P < 0.001) in CuD rats than in CuA rats. Duodenal mucosa and liver Fe were higher (P < 0.01) in CuD male rats than CuA rats. Duodenal Fe but not liver Fe was higher in CuD female rats than CuA rats. Liver Fe was much higher (<0.001) overall in females than males. The data suggest that Cu deficiency reduces Fe absorption in rats through reduced expression of duodenal Hp protein. PMID:15623839

  16. Endurance exercise facilitates relearning of forelimb motor skill after focal ischemia.

    PubMed

    Ploughman, Michelle; Attwood, Zachary; White, Nicole; Doré, Jules J E; Corbett, Dale

    2007-06-01

    Endurance exercise (i.e. running), by up-regulating brain-derived neurotrophic factor (BDNF) and other modulators of synaptic plasticity, improves attention and learning, both critical components of stroke rehabilitation. We hypothesized that, following middle cerebral artery occlusion in male Sprague-Dawley rats, endurance exercise would act synergistically with a challenging skilled forelimb task to facilitate motor recovery. Animals were randomly assigned to one of four rehabilitation conditions: no rehabilitation, running only, reach training only, and reach training preceded by running (run/reach training) for 5 weeks beginning 5 days after stroke. The behavioral outcome, morphological change and mRNA expression of proteins implicated in neuroplasticity (BDNF, synapsin I and microtubule-associated protein 2) were compared. Endurance exercise on a motorized running wheel, prior to reach training, enhanced recovery of skilled reaching ability but did not transfer to gross motor skills such as postural support (forelimb asymmetry test) and gait (ladder rung walking test). Microtubule-associated protein 2 staining density in the run/reach group was slightly enhanced in the contralateral motor cortex compared with the contralateral sensory and ipsilateral cingulate cortices, suggesting that running preceding reach training may have resulted in more dendritic branching within the motor cortex in this group. No significant differences in mRNA levels were detected among the training paradigms; however, there was a trend toward greater BDNF and synapsin I mRNA in the reaching groups. These findings suggest that exercise facilitates learning of subsequent challenging reaching tasks after stroke, which has the potential to optimize outcomes in patients with stroke. PMID:17553014

  17. 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…

  18. Constraints on Mammalian forelimb development: insights from developmental disparity.

    PubMed

    Ross, Darcy; Marcot, Jonathan D; Betteridge, Keith J; Nascone-Yoder, Nanette; Bailey, C Scott; Sears, Karen E

    2013-12-01

    Tetrapod limb development has been studied extensively for decades, yet the strength and role of developmental constraints in this process remains unresolved. Mammals exhibit a particularly wide array of limb morphologies associated with various locomotion modes and behaviors, providing a useful system for identifying periods of developmental constraint and conserved developmental mechanisms or morphologies. In this study, landmark-based geometric morphometrics are used to investigate levels and patterns of morphological diversity (disparity) among the developing forelimbs of four mammals with diverse limb morphologies: mice, opossums, horses, and pigs. Results indicate that disparity among the forelimbs of these species slightly decreases or stays the same from the appearance of the limb ridge to the bud stage, and increases dramatically from the paddle through tissue regression stages. Heterochrony exhibited by the precocial opossum limb was not found to drive these patterns of morphological disparity, suggesting that the low disparity of the middle stages of limb development (e.g., paddle stage) is driven by processes operating within the limb and is likely not a result of embryo-wide constraint. PMID:24299415

  19. Functional anatomy of the cheetah (Acinonyx jubatus) forelimb.

    PubMed

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

    2011-04-01

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

  20. Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs

    PubMed Central

    Liu, Shiqiu; Smith, Adam S.; Gu, Yuting; Tan, Jie; Liu, C. Karen; Turk, Greg

    2015-01-01

    Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability. PMID:26683221

  1. Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs.

    PubMed

    Liu, Shiqiu; Smith, Adam S; Gu, Yuting; Tan, Jie; Liu, C Karen; Turk, Greg

    2015-12-01

    Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability. PMID:26683221

  2. Comparative myology of the forelimb of squirrels (Sciuridae).

    PubMed

    Thorington, R W; Darrow, K; Betts, A D

    1997-11-01

    The musculature of the shoulder, arm, and forearm was studied in 19 genera of squirrels, representing the Pteromyinae (flying squirrels) and all 7 tribes of the Sciurinae (tree and ground squirrels). The objective was to locate derived anatomical features of functional or phylogenetic significance and to determine how much morphological variation underlies the diverse locomotor behavior of squirrels, which includes terrestrial and arboreal bounding, climbing, digging, and gliding. The fossil evidence suggests that arboreality is primitive for squirrels, and in fact tree squirrels appear to represent the primitive sciurid morphology. Ground squirrels are less uniform and exhibit a few derived features, including a clavobrachialis muscle not seen in other squirrels. Pygmy tree squirrels, which have evolved independently in three tribes, exhibit convergence of forelimb anatomy, including the loss or reduction of several muscles in the shoulder and forearm. The forelimb anatomy of flying squirrels is the most derived and differs from that of tree squirrels in details of shoulder, arm, and forearm musculature. Some of these muscular differences among squirrels have phylogenetic significance, being shared by closely related genera, but none has significance above the tribal level. Many of the differences suggest a variety of changes in function that are amenable to further study. PMID:9360319

  3. Immediate Postsession Feeding Reduces Operant Responding in Rats

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  4. 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.

  5. 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…

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

    PubMed

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

    2012-01-01

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

  7. 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 TNFα 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 TNFα 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

  8. Apc-driven colon carcinogenesis in Pirc rat is strongly reduced by polyethylene glycol.

    PubMed

    Femia, Angelo Pietro; Becherucci, Caterina; Crucitta, Stefania; Caderni, Giovanna

    2015-11-01

    Polyethylene glycol (PEG) is one of the most powerful agents in reducing chemically induced carcinogenesis in rat colon. However, contrasting results in Min mice dampened the enthusiasm on this potentially strong and virtually safe, cancer chemopreventing agent. Pirc (F344/NTac-Apc (am1137) ) rats carrying a germline heterozygous mutation in the Apc gene, spontaneously develop multiple tumours in the colon thus modelling both familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC). Given this similarity, we thought that these rats could be appropriate to test the efficacy of PEG 8000 in reducing carcinogenesis. Pirc male rats aged one month were treated with 5% PEG in drinking water for 2 or 6 months. Precancerous lesions were dramatically reduced after 2 months of PEG treatment (Mucin depleted foci (MDF)/colon were 99 ± 17 and 12 ± 8 in Controls and PEG-treated rats, respectively; p < 0.001; mean ± SD). Similarly, colon tumors were significantly reduced after 6 months of treatment (tumors/rat were 8.1 ± 2.3 and 3.6 ± 2.2 in Controls and PEG-treated rats, respectively; p < 0.05; mean ± SD). Colon proliferation, a parameter correlated to cancer risk, was also significantly lower in PEG-treated rats than in Controls, while apoptosis was not significantly affected. In conclusion, PEG markedly reduces colon carcinogenesis in Pirc rats mutated in Apc; we thus suggest that PEG may be used as chemopreventive agent to reduce cancer risk in FAP and CRC patients. PMID:25912754

  9. Robotic Rehabilitator of the Rodent Upper Extremity: A System and Method for Assessing and Training Forelimb Force Production after Neurological Injury.

    PubMed

    Sharp, Kelli G; Duarte, Jaime E; Gebrekristos, Berkenesh; Perez, Sergi; Steward, Oswald; Reinkensmeyer, David J

    2016-03-01

    Rodent models of spinal cord injury are critical for the development of treatments for upper limb motor impairment in humans, but there are few methods for measuring forelimb strength of rodents, an important outcome measure. We developed a novel robotic device--the Robotic Rehabilitator of the Rodent Upper Extremity (RUE)--that requires rats to voluntarily reach for and pull a bar to retrieve a food reward; the resistance of the bar can be programmed. We used RUE to train forelimb strength of 16 rats three times per week for 23 weeks before and 38 weeks after a mild (100 kdyne) unilateral contusion at the cervical level 5 (C5). We measured maximum force produced when RUE movement was unexpectedly blocked. We compared this blocked pulling force (BPF) to weekly measures of forelimb strength obtained with a previous, well-established method: the grip strength meter (GSM). Before injury, BPF was 2.6 times higher (BPF, 444.6 ± 19.1 g; GSM, 168.4 ± 3.1 g) and 4.9 times more variable (p < 0.001) than pulling force measured with the GSM; the two measurement methods were uncorrelated (R(2) = 0.03; p = 0.84). After injury, there was a significant decrease in BPF of 134.35 g ± 14.71 g (p < 0.001). Together, our findings document BPF as a repeatable measure of forelimb force production, sensitive to a mild spinal cord injury, which comes closer to measuring maximum force than the GSM and thus may provide a useful measure for quantifying the effects of treatment in rodent models of SCI. PMID:26414700

  10. Peripheral oxytocin administration reduces ethanol consumption in rats

    PubMed Central

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague–Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose–response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5 mg/kg (I.P.). Next, rats received 0.3 mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3 mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism. PMID:26519603

  11. Hippocampal long-term potentiation is reduced in mature compared to young male rats but not in female rats.

    PubMed

    Monfort, P; Felipo, V

    2007-05-11

    Aging is associated with a decline in cognitive function which could be due to reduced synaptic plasticity. Hippocampal long-term potentiation (LTP) is an activity-dependent form of increased transmission efficacy at synapses that is considered the basis for some forms of learning and memory. We studied the N-methyl-d-aspartic acid (NMDA) receptor-dependent LTP in the CA1 region of hippocampus in young (2 months) and mature (8 months) male and female rats. We have found that in young male rats the tetanus increased the magnitude of excitatory post-synaptic potentials to 204+/-10% of basal while in mature male rats the magnitude of the LTP was significantly lower reaching only 153+/-11% of basal. This decrease did not occur in female rats. Similar changes occurred in the content of the NMDA receptor subunits NR1 and NR2A in hippocampus. The amount of both subunits was reduced significantly (15-16%) in hippocampus of 8-month-old compared with 2-month-old male rats. This decrease was not observed in female rats. Moreover, there is a significant correlation between the content of NR1 subunit and the magnitude of the potentiation. These data suggest that some of the neurobiological changes induced in hippocampus by aging are different in males and females. PMID:17395392

  12. Blood-brain barrier transport of choline is reduced in the aged rat.

    PubMed

    Mooradian, A D

    1988-02-01

    An age-related impairment in choline transport across the blood-brain barrier (BBB) may contribute to the cholinergic mechanisms of geriatric memory dysfunction. To test this hypothesis, the brain choline uptake in male Fisher 344 rats at 2, 18 and 24 months of age was studied using the Oldendorf technique. The Vmax of choline transport in the 24-month-old rats (0.05 +/- 0.04 nmol/min/g) was significantly lower than that in the 2-month-old rat (2.5 +/- 1.0 nmol/min/g) (P less than 0.05). The Km of transport in old rats (13 +/- 35 microM) was also significantly smaller than the value in 24-month-old rats (450 +/- 195 microM), while the constant of the non-saturable component of the transport, Kd, was not significantly different in older rats (1.2 +/- 0.3 vs 0.6 +/- 0.1 microliter/min/g). These results indicate that the carrier in old rats has reduced capacity and increased affinity to choline. The reduced choline carrier capacity explains the significant decrease in BBB choline transport in aged rats. PMID:3359216

  13. Transgenic mice ectopically expressing HOXA5 in the dorsal spinal cord show structural defects of the cervical spinal cord along with sensory and motor defects of the forelimb.

    PubMed

    Krieger, Karin E; Abbott, Matthew A; Joksimovic, Milan; Lueth, Paul A; Sonea, Ioana M; Jeannotte, Lucie; Tuggle, Christopher K

    2004-06-21

    Mutation of murine Hoxa5 has shown that HOXA5 controls lung, gastrointestinal tract and vertebrae development. Hoxa5 is also expressed in the spinal cord, yet no central nervous system phenotype has been described in Hoxa5 knockouts. To identify the role of Hoxa5 in spinal cord development, we developed transgenic mice that express HOXA5 in the dorsal spinal cord in the brachial region. Using HOXA5-specific antibodies, we show this expression pattern is ectopic as the endogenous protein is expressed only in the ventral spinal cord at this anterio-posterior level. This transgenic line (Hoxa5SV2) also displays forelimb-specific motor and sensory defects. Hoxa5SV2 transgenic mice cannot support their body weight in a forelimb hang, and forelimb strength is decreased. However, Rotarod performance was not impaired in Hoxa5SV2 mice. Hoxa5SV2 mice also show a delayed forelimb response to noxious heat, although hindlimb response time was normal. Administration of an analgesic significantly reduced the hang test defect and decreased the transgene effect on forelimb strength, indicating that pain pathways may be affected. The morphology of transgenic cervical (but not lumbar) spinal cord is highly aberrant. Nissl staining indicates superficial laminae of the dorsal horn are severely disrupted. The distribution of cells and axons immunoreactive for substance P, neurokinin-B, and their primary receptors were aberrant only in transgenic cervical spinal cord. Further, we see increased levels of apoptosis in transgenic spinal cord at embryonic day 13.5. Our evidence suggests apoptosis due to HOXA5 misexpression is a major cause of loss of superficial lamina cells in Hoxa5SV2 mice. PMID:15158076

  14. Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.

    PubMed

    Kaysen, G A; Hoye, E; Jones, H

    1995-03-01

    Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats. PMID:7900854

  15. Morphological integration in the forelimb of musteloid carnivorans

    PubMed Central

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

    2014-01-01

    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

  16. Forelimb skeletal morphology and flight mode evolution in pelecaniform birds.

    PubMed

    Simons, Erin L R

    2010-01-01

    The total length and mid-shaft diameters of wing elements of 50 species of pelecaniform birds were examined to investigate how forelimb skeletal morphology varies with body size and flight mode within this group. Pelecaniforms were assigned to flight mode categories based on primary habitual behaviors (soar, flap-glide, continuous flap). Allometric and discriminant function analyses were conducted on wing element variables in both historical (using independent contrasts) and ahistorical contexts. Results of this study indicate that when phylogenetic relationships are taken into account, only the length of the ulna scales with positive allometry, whereas all other variables exhibit isometry. These results differ from the ahistorical allometric analysis. Discriminant function analysis (DFA) significantly separated the flight mode groups (Wilk's lambda=0.002, p<0.00001), with only six individuals from two species (out of n=284) misclassified. Results of historical canonical variates analysis supported the ahistorical DFA and identified two carpometacarpal (CMC) variables as important for separating the flight mode groups: dorsoventral CMC diameter and total CMC length. The carpometacarpus is that portion of the forelimb skeleton that serves as the attachment point for the primary flight feathers, and thus, that portion of the airfoil surface that mediates detailed flight control. Its morphology, more than any other element, reflects differences in flight mode in pelecaniforms. Results of this study indicate that, in pelecaniforms, wing bones generally exhibit isometry (with the exception of the ulna) and do possess specific morphologies reflective of the demands associated with different types of aerial locomotor specialization. PMID:20071157

  17. The “good” limb makes the “bad” limb worse: Experience-dependent interhemispheric disruption of functional outcome after cortical infarcts in rats

    PubMed Central

    Allred, R.P.; Cappellini, C.H.; Jones, T.A.

    2016-01-01

    Following stroke-like lesions to the sensorimotor cortex in rats, experience with the ipsi-to-lesion (ipsilesional, “nonparetic”) forelimb worsens deficits in the contralesional (“paretic”) forelimb. We tested whether the maladaptive effects of experience with the nonparetic limb are mediated through callosal connections and the contralesional sensorimotor cortex. Adult male rats with proficiency in skilled reaching with their dominant (for reaching) forelimb received ischemic bilateral sensorimotor cortex lesions, or unilateral lesions with or without callosal transections. After assessing dominant forelimb function (the paretic forelimb in rats with unilateral lesions), animals were trained with their non-dominant/nonparetic forelimb or underwent control procedures for 15 days. Animals were then tested with their dominant/paretic forelimb. In animals with unilateral lesions only, nonparetic forelimb training worsened subsequent performance with the paretic forelimb, as found previously. This effect was not found in animals with both callosal transections and unilateral lesions. After bilateral lesions, training the non-dominant limb did not worsen function of the dominant limb compared with controls. Thus, the maladaptive effects of training the nonparetic limb on paretic forelimb function depend upon the contralesional cortex and transcallosal projections. This suggests that this experience-dependent disruption of functional recovery is mediated through interhemispheric connections of the sensorimotor cortex. PMID:20141287

  18. Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats.

    PubMed

    Tsuyoshi, Hideaki; Orisaka, Makoto; Fukuda, Shin; Hattori, Katsushige; Tsang, Benjamin K; Yoshida, Yoshio

    2015-01-01

    Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy. PMID:25449767

  19. Motor and postural asymmetries in marsupials: Forelimb preferences in the red-necked wallaby (Macropus rufogriseus).

    PubMed

    Spiezio, Caterina; Regaiolli, Barbara; Vallortigara, Giorgio

    2016-07-01

    In the last decades, several studies on mammal motor lateralization have been carried out. However, data on marsupials are still underrepresented in the literature, despite their importance in tracing the evolution of motor laterality and its functional value. This study aimed at investigating motor lateralization in a sample of captive red-necked wallabies (Macropus rufogriseus), considering different daily unimanual activities and forelimb implication in postural support. Data on forelimb preference for food reaching, pulling food out of the mouth, self-scratching and starting locomotion from quadrupedal posture were collected; furthermore, to investigate the role of posture in determining the forelimb laterality of wallabies, data on forelimb use for postural support in tripedal stance were recorded. Our results revealed significant group-level left forelimb preferences for self-scratching and starting locomotion, as well as for providing postural support in tripedal stance. These results are discussed in the light of theories for a right hemisphere dominance for emotion processing and for postural influences on forelimb dominance throughout evolution. The reported left biases in forelimb use for different behaviours are in agreement with previous literature on macropods. PMID:27150458

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

    PubMed

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

    2005-01-01

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

  1. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Ghareeb, Doaa A.; Khalil, Sofia; Hafez, Hani S.; Bajorath, Jürgen; Ahmed, Hany E. A.; Sarhan, Eman; Elwakeel, Eiman; El-Demellawy, Maha A.

    2015-01-01

    Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (Aβ40) and increased beta-amyloid42 (Aβ42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity. PMID:26576191

  2. Xiayuxue decoction reduces renal injury by promoting macrophage apoptosis in hepatic cirrhotic rats.

    PubMed

    Liu, C; Cai, J; Cheng, Z; Dai, X; Tao, L; Zhang, J; Xue, D

    2015-01-01

    Renal pathological changes in cirrhotic rat have not been extensively reported. The aim of this study was to investigate whether Xiayuxue decoction (XYXD) could attenuate renal injury induced by bile duct ligation (BDL), with special focus on the mechanisms promoting renal macrophage apoptosis. The rats were treated with BDL for 5 weeks and administered 0.36 g/kg XYXD intragastrically from day 1 of initiating BDL. Renal tissue was monitored by hematoxylin-eosin and Sirius red staining. Macrophage infiltration and proinflammatory cytokines such as tumor necrosis factor and chemokine ligand 2 were detected by quantitative polymerase chain reaction. Macrophage apoptosis was detected by double immunofluorescence staining. Blood urea nitrogen, creatinine, and glomerulus diameter increased significantly after a 5-week BDL treatment in XYXD (BDL-XYXD) rats. CD68 and pro-inflammatory cytokine mRNA increased in the kidneys of control (BDL-water) rats. Fluorescence microscopy analysis showed that XYXD promoted apoptosis in renal CD68+ macrophages. Collogen1 (Col 1), pro-fibrogenic cytokines, and α-smooth muscle actin in kidneys of BDL-water rats increased significantly compared to the sham group. XYXD inhibited Col 1 and pro-fibrotic factors in BDL-XYXD rats. Our results demonstrated that XYXD significantly reduced renal injury by, at least in part, promoting macrophage apoptosis in rats with damaged renal histopathology due to BDL-induced cirrhosis. PMID:26400305

  3. ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

    PubMed Central

    Porritt, Michelle J; Chen, Michelle; Rewell, Sarah S J; Dean, Rachael G; Burrell, Louise M; Howells, David W

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR. PMID:20407464

  4. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

    PubMed

    Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2016-01-01

    Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression. PMID:27579183

  5. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

    PubMed Central

    Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2016-01-01

    Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression. PMID:27579183

  6. Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

    PubMed Central

    Cissé, Youssouf; Inoue, Isao; Kido, Hiroshi

    2012-01-01

    Background Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. Objective The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. Methods Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. Results We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. Conclusion Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

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

    PubMed Central

    2014-01-01

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

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.; Thomas, Joshua D.

    2014-12-01

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

  10. Swim therapy reduces mechanical allodynia and thermal hyperalgesia induced by chronic constriction nerve injury in rats

    PubMed Central

    Shen, Jun; Fox, Lyle E.; Cheng, Jianguo

    2013-01-01

    Objective Neuropathic pain is common and often difficult to treat because it generally does not respond well to the currently available pain medications or nerve blocks. Recent studies in both humans and animals have suggested that exercise may induce a transient analgesia and reduce acute pain in normal healthy individuals. We examined whether swim therapy could alleviate neuropathic pain in rats. Design Rats were trained to swim over a two week period in warm water. After the rats were trained, neuropathic pain was induced by constricting the right sciatic nerve and regular swimming was resumed. The sensitivity of each hind paw was monitored using the Hargreaves test and von Frey test to evaluate the withdrawal response thresholds to heat and touch. Results The paw ipsilateral to the nerve ligation expressed pain-like behaviors including thermal hyperalgesia and mechanical allodynia. Regular swim therapy sessions significantly reduced the mechanical allodynia and thermal hyperalgesia. Swim therapy had little effect on the withdrawal thresholds for the contralateral paw. In addition, swim therapy alone did not alter the thermal or mechanical thresholds of normal rats. Conclusions The results suggest that regular exercise, including swim therapy, may be an effective treatment for neuropathic pain caused by nerve injuries. This study, showing that swim therapy reduces neuropathic pain behavior in rats, provides a scientific rationale for clinicians to test the efficacy of exercise in the management of neuropathic pain. It may prove to be a safe and cost-effective therapy in a variety of neuropathic pain states. PMID:23438327

  11. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively. PMID:25157962

  12. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats.

    PubMed

    Guo, Lili; Shi, Mingyi; Zhang, Ling; Li, Guangzhi; Zhang, Lingxiang; Shao, Hu; Fang, Penghua; Ma, Yingping; Li, Jian; Shi, Qiaojia; Sui, Yumei

    2011-08-01

    Seeing that galanin increases animal body weight on the conditions of inhibiting insulin secretion and animals with metabolic disorder of galanin easily suffer from diabetes, we postulate that endogenous galanin is necessary to reduce insulin resistance in adipocytes. To test this hypothesis, we compared four groups of rats to examine whether an increase in galanin secretion stimulated by swimming may reduce insulin resistance. The rats from sedentary and trained drug groups were injected by M35, a galanin antagonist. The rats from trained control and trained drug groups swam after each injection for four weeks. We found that exercise significantly elevated plasma galanin contents and glucose transporter 4 (GLUT4) mRNA levels in adipocytes. Meanwhile, M35 treatment reduced GLUT4 and GLUT4 mRNA levels, and glucose infusing rates in euglycemic-hyperinsulinemic clamp tests. The ratios of GLUT4 concentrations at plasma membranes to total cell membranes in both drug groups were lower compared with each control group, respectively. These observations suggest that endogenous galanin reduces insulin resistance by increasing GLUT4 contents and promoting GLUT4 transportation from intracellular membranes to plasma membranes in adipocytes. Galanin is an important hormone to reduce insulin resistance in rats. PMID:21664358

  13. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity.

    PubMed

    Ji, Hong; Friedman, Mark I

    2007-08-01

    High-fat, energy-dense diets promote weight gain and obesity in humans and other animals, but the mechanisms underlying such diet-induced obesity remain elusive. To determine whether a reduced capacity to oxidize fat is involved in the etiology of diet-induced obesity, we examined different measures of fatty acid oxidation in rats selectively bred for susceptibility (DIO) or resistance (DR) to dietary obesity before and after they were fed a high-fat diet and became obese. DIO rats eating a low-fat diet oxidized less dietary fatty acid in vivo and had lower levels of plasma ketone bodies during fasting compared with DR rats. Lean DIO rats fed a low-fat diet showed reduced liver messenger RNA expression of CD36, which transports fatty acids across cell membranes, and long-chain acyl-coenzyme A dehydrogenase (ACADL), which catalyzes the first step in the mitochondrial beta-oxidation of fatty acids. The deficit in CD36 and ACADL messenger RNA expression was also seen in obese DIO rats that had been eating a high-fat diet and, in addition, was accompanied by reduced expression of liver carnitine palmitoyl transferase I, the enzyme that mediates transport of long-chain fatty acids into mitochondria. No differences were found in the expression of liver enzymes involved in fat synthesis; however, in muscle, DIO rats fed the low-fat, but not high-fat, diet showed greater expression of diacylglycerol O-acyltransferase 1 and lipoprotein lipase than did DR rats. Expression of muscle enzymes involved in fatty acid oxidation was similar in the 2 groups. These findings provide a metabolic mechanism for the development of diet-induced obesity and thus suggest potential targets for intervention strategies to treat or prevent it. PMID:17618960

  14. Comparative kinematics of the forelimb during swimming in red-eared slider (Trachemys scripta) and spiny softshell (Apalone spinifera) turtles.

    PubMed

    Pace, C M; Blob, R W; Westneat, M W

    2001-10-01

    Softshell turtles (Family Trionychidae) possess extensive webbing between the digits of the manus, suggesting that the forelimb may serve as an effective thrust generator during aquatic locomotion. However, the hindlimb has previously been viewed as the dominant propulsive organ in swimming freshwater turtles. To evaluate the potential role of the forelimb in thrust production during swimming in freshwater turtles, we compared the forelimb morphology and three-dimensional forelimb kinematics of a highly aquatic trionychid turtle, the spiny softshell Apalone spinifera, and a morphologically generalized emydid turtle, the red-eared slider Trachemys scripta. Spiny softshells possess nearly twice as much forelimb surface area as sliders for generating drag-based thrust. In addition, although both species use drag-based propulsion, several aspects of forelimb kinematics differ significantly between these species. During the thrust phase of the forelimb cycle, spiny softshells hold the elbow and wrist joints significantly straighter than sliders, thereby further increasing the surface area of the limb that can move water posteriorly and increasing the velocity of the distal portion of the forelimb. These aspects of swimming kinematics in softshells should increase forelimb thrust production and suggest that the forelimbs make more substantial contributions to forward thrust in softshell turtles than in sliders. Spiny softshells also restrict forelimb movements to a much narrower dorsoventral and anteroposterior range than sliders throughout the stroke, thereby helping to minimize limb movements potentially extraneous to forward thrust production. These comparisons demonstrate considerable diversity in the forelimb kinematics of turtles that swim using rowing motions of the limbs and suggest that the evolution of turtle forelimb mechanics produced a variety of contrasting solutions for aquatic specialization. PMID:11606600

  15. Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis.

    PubMed

    Nardelli, Paul; Vincent, Jacob A; Powers, Randall; Cope, Tim C; Rich, Mark M

    2016-08-01

    The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron excitability and compared its magnitude to the contributions of myopathy, neuropathy and failure of neuromuscular transmission. We injected constant depolarizing current pulses (5s) into the soma of alpha motor neurons in the lumbosacral spinal cord of anesthetized rats to trigger repetitive firing. In response to constant depolarization, motor neurons in untreated control rats fired at steady and continuous firing rates and generated smooth and sustained tetanic motor unit force as expected. In contrast, following induction of sepsis, motor neurons were often unable to sustain firing throughout the 5s current injection such that force production was reduced. Even when firing, motor neurons from septic rats fired erratically and discontinuously, leading to irregular production of motor unit force. Both fast and slow type motor neurons had similar disruption of excitability. We followed rats after recovery from sepsis to determine the time course of resolution of the defect in motor neuron excitability. By one week, rats appeared to have recovered from sepsis as they had no piloerection and appeared to be in no distress. The defects in motor neuron repetitive firing were still striking at 2weeks and, although improved, were present at one month. We infer that rats suffered from weakness due to reduced

  16. TRH injected into the nucleus accumbens shell releases dopamine and reduces feeding motivation in rats.

    PubMed

    Puga, L; Alcántara-Alonso, V; Coffeen, U; Jaimes, O; de Gortari, P

    2016-06-01

    The thyrotropin-releasing hormone (TRH), an anorexigenic factor that reduces food intake in food-restricted animals, may be involved in motivation for food. Injected centrally, TRH impairs acquisition of food-rewarded behavior. Through the TRH-R1 receptors, TRH injected in the nucleus accumbens increases dopamine content-perhaps the mechanism by which the peptide modulates food motivation. This, however, is still to be demonstrated. We sought to evaluate dopamine release by microdialysis after a TRH injection into the nucleus accumbens shell in free-moving fasted rats. In addition, we assessed dopamine content and turnover by HPLC and the relationship with the motivation for food by analyzing the performance of rats during a progressive-ratio (PR) operant-conditioning test. Finally, we determined serum leptin and triiodothyronine (T3) levels in order to evaluate the animals' metabolic response to food restriction and the impact of intra-accumbal TRH administration on circulating hormones. Intra-accumbal injections of TRH reduced food intake in food-restricted rats-compared to counterparts treated with saline-, without further decreasing T3 or leptin levels, which dropped due to their dietary regime. TRH-injected rats had lower breaking points on the PR schedule, which indicated lower motivation to eat. Accordingly, compared to saline-treated animals, dopamine release and turnover increased in the nucleus accumbens of TRH-injected rats, a finding that suggests a relationship between motivation for food and TRH-induced release of dopamine. PMID:27006143

  17. 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

  18. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    PubMed Central

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  19. Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats.

    PubMed

    Choi, Joo Sun; Koh, In-Uk; Song, Jihyun

    2012-11-01

    Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and carnitine palmitoyltransferase and the rate of β-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance. PMID:23176795

  20. NOS inhibition increases bubble formation and reduces survival in sedentary but not exercised rats

    PubMed Central

    Wisløff, Ulrik; Richardson, Russell S; Brubakk, Alf O

    2003-01-01

    Previously we have shown that chronic as well as a single bout of exercise 20 h prior to a simulated dive protects rats from severe decompression illness (DCI) and death. However, the mechanism behind this protection is still not known. The present study determines the effect of inhibiting nitric oxide synthase (NOS) on bubble formation in acutely exercised and sedentary rats exposed to hyperbaric pressure. A total of 45 adult female Sprague-Dawley rats (270-320 g) were randomly assigned into exercise or sedentary control groups, with and without NOS inhibition, using l-NAME (0.05 or 1 mg ml−1) (a nonselective NOS inhibitor). Exercising rats ran intervals on a treadmill for 1.5 h, 20 h prior to the simulated dive. Intervals alternated between 8 min at 85–90 % of maximal oxygen uptake, and 2 min at 50–60 %. Rats were compressed (simulated dive) in a pressure chamber, at a rate of 200 kPa min−1 to a pressure of 700 kPa, and maintained for 45 min breathing air. At the end of the exposure period, rats were decompressed linearly to the ‘surface’ (100 kPa) at a rate of 50 kPa min−1. Immediately after reaching the surface the animals were anaesthetised and the right ventricle was insonated using ultrasound. The study demonstrated that sedentary rats weighing more than 300 g produced a large amount of bubbles, while those weighing less than 300 g produced few bubbles and most survived the protocol. Prior exercise reduced bubble formation and increased survival in rats weighing more than 300 g, confirming the results from the previous study. During NOS inhibition, the simulated dive induced significantly more bubbles in all sedentary rats weighing less than 300 g. However, this effect could be attenuated by a single bout of exercise 20 h before exposure. The present study demonstrates two previously unreported findings: that administration of l-NAME allows substantial bubble formation and decreased survival in sedentary rats, and that a single bout of exercise

  1. Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency.

    PubMed

    Cordeiro, Karina Kohn; Jiang, Wei; Papazoglou, Anna; Tenório, Sérgio Bernardo; Döbrössy, Máté; Nikkhah, Guido

    2010-10-15

    The Staircase test measures lateralised deficits in skilled paw reaching in rodents, and there is a long-standing discrepancy in the literature on whether the paradigm is sensitive to graft-mediated functional recovery in the rodent model of Parkinson's disease. The aim of the current study was to evaluate the critical influence of test conditions like pellet density on dopamine-dependent graft-mediated functional recovery. Rats were pre-trained on the Staircase test with a configuration of 8 pellets in each of the 6 wells bilaterally prior to receiving unilateral 6-OHDA lesions of the medial forebrain bundle. Later, the lesioned animals received E14 VM grafts into the striatum, and were tested on the Staircase test under one of two test configurations: bilaterally, either with 10 (HIGH) or with 2 (LOW) pellets per well. Subsequent sessions included unilateral forced-choice testing under the same pellet configuration, and second bilateral and forced-choice sessions with the pellet density configurations switched around between the groups (Cross-over). Animals were also tested on the Corridor and the Cylinder test, and subjected to drug-induced rotation. Graft-mediated functional recovery was observed in the pellets taken criteria only under the HIGH pellet configuration during the bilateral and the forced choice condition. When tested under the LOW configuration, the graft provided no measurable benefit. The presence of VM grafts reduced lateralised motor deficits in the Cylinder test, the adjacent version of the Corridor test, and drug-induced rotation. Our results confirm that VM transplants can partially restore skilled forelimb sensorimotor deficits under specific testing configuration. PMID:20394782

  2. Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

    PubMed Central

    Akcan, Alper; Kucuk, Can; Sozuer, Erdogan; Esel, Duygu; Akyildiz, Hizir; Akgun, Hulya; Muhtaroglu, Sabahattin; Aritas, Yucel

    2008-01-01

    AIM: To investigate the effects of exogenous melatonin on bacterial translocation and apoptosis in a rat ulcerative colitis model. METHODS: Rats were randomly assigned to three groups: groupI: control, group II: experimental colitis, group III: colitis plus melatonin treatment. On d 11 after colitis, plasma tumor necrosis factor-α, portal blood endotoxin levels, colon tissue myeloperoxidase and caspase-3 activity were measured. Bacterial translocation was quantified by blood, lymph node, liver and spleen culture. RESULTS: We observed a significantly reduced incidence of bacterial translocation to the liver, spleen, mesenteric lymph nodes, portal and systemic blood in animals treated with melatonin. Treatment with melatonin significantly decreased the caspase-3 activity in colonic tissues compared to that in trinitrobenzene sulphonic acid- treated rats (16.11 ± 2.46 vs 32.97 ± 3.91, P < 0.01). CONCLUSION: Melatonin has a protective effect on bacterial translocation and apoptosis. PMID:18240350

  3. Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

    PubMed Central

    Deng, Quan-Jun; Deng, Ding-Jing; Che, Jin; Zhao, Hai-Rong; Yu, Jun-Jie; Lu, Yong-Yu

    2016-01-01

    AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in

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

    PubMed Central

    Wisløff, Ulrik; Brubakk, Alf O

    2001-01-01

    The formation of bubbles is the basis for injury to divers after decompression, a condition known as decompression illness. In the present study we investigated the effect of endurance training in the rat on decompression-induced bubble formation. A total of 52 adult female Sprague-Dawley rats (300-370 g) were randomly assigned to one of two experimental groups: training or sedentary control. Trained rats exercised on a treadmill for 1.5 h per day for 1 day, or for 2 or 6 weeks (5 days per week) at exercise intervals that alternated between 8 min at 85-90 % of maximal oxygen uptake (V̇O2,max) and 2 min at 50-60 % of V̇O2,max. Rats were compressed (simulated dive) in a decompression chamber in pairs, one sedentary and one trained, at a rate of 200 kPa min−1 to a pressure of 700 kPa, and maintained for 45 min breathing air. At the end of the exposure period, rats were decompressed linearly to the ‘surface’ (100 kPa) at a rate of 50 kPa min−1. Immediately after reaching the ‘surface’ (100 kPa) the animals were anaesthetized and the right ventricle was insonated using Doppler ultrasound. Intensity-controlled interval training significantly increased V̇O2,max by 12 and 60 % after 2 and 6 weeks, respectively. At 6 weeks, left and right ventricular weights were 14 and 17 % higher, respectively, in trained compared to control rats. No effect of training was observed on skeletal muscle weight. Bubble formation was significantly reduced in trained rats after both 2 and 6 weeks. However, the same effect was seen after a single bout of aerobic exercise lasting 1.5 h on the day prior to decompression. All of the rats that exercised for 1.5 h and 2 weeks, and most of those that trained for 6 weeks, survived the protocol, whereas most sedentary rats died within 60 min post-decompression. This study shows that aerobic exercise protects rats from severe decompression and death. This may be a result of less bubbling in the trained animals. The data showed that the

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

    PubMed Central

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

    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 (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

  6. 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

  7. MAG-EPA reduces severity of DSS-induced colitis in rats.

    PubMed

    Morin, Caroline; Blier, Pierre U; Fortin, Samuel

    2016-05-15

    Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats. PMID:27012773

  8. Vitamin E reduces glucocorticoid-induced growth inhibition and lipid peroxidation in rats.

    PubMed

    Ohtsuka, A; Ohtani, T; Horiguchi, H; Kojima, H; Hayashi, K

    1998-04-01

    This experiment was conducted to study the effects of vitamin E on growth inhibition and lipid peroxidation in rats treated with different levels of corticosterone (CTC). Rats (Sprague-Dawley strain, 5 weeks of age) were divided into two groups: control group receiving a basal diet containing 60 mg DL-alpha-tocopheryl acetate/kg diet, and vitamin E group receiving the same diet supplemented with 5,000 mg tocopherol. After 6 days, rats of both diet groups were further divided into three groups by dose levels of CTC treatment (0, 25, and 100 mg CTC/kg body weight/d). CTC was administered to the rats by subcutaneous injection for 4 d. Growth was dose-dependently inhibited by the CTC treatment. Feeding the vitamin E diet significantly (p < 0.05) improved growth retardation. Feed efficiency was lowered by CTC treatment, while this was significantly (p < 0.05) minimized by feeding the vitamin E diet. Lipid peroxidation (TBARS) in the liver was elevated by the CTC treatment (p < 0.001) when the rats were fed the basal diet. The increment in TBARS was significantly (p < 0.001) reduced by vitamin E. The activities of glutathione S-transferase (GST) and superoxide dismutase (SOD) were significantly reduced by the CTC treatment in a dose-dependent manner in both dietary groups. Feeding vitamin E significantly (p < 0.001) improved the reduction in GST activity. The SOD activity showed some tendency. The present results demonstrate the effectiveness of vitamin E in improving growth retardation in glucocorticoid-treated rats and suggest that reductions in increased lipid peroxidation due to CTC may be an important factor of the action of vitamin E. PMID:9675704

  9. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

    PubMed Central

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

  10. Early social and physical deprivation leads to reduced social motivation in adulthood in Wistar rats.

    PubMed

    Mintz, Matti; Rüedi-Bettschen, Daniela; Feldon, Joram; Pryce, Christopher R

    2005-01-30

    Behavioural abnormalities in adulthood may have their origin in a disturbed interaction with the environment during postnatal development. We tested the consequences for adult social motivation of early deprivation (ED) of rat pups from mothers and littermates relative to nonhandled (NH) pups. Early deprivation was performed at room or warm ambient temperatures, cold-ED and warm-ED, respectively, and during either the dark or light phase of the daily cycle. In adulthood, rats that were unrelated and unfamiliar but of the same treatment group were introduced in pairs to an open field for a 30-min test. Social behaviour in home base and exploration modes was assessed using algorithmic analysis of the XY locations of the two rats. Findings revealed that Cold-ED induced a preference for a separate home base, which limited significantly the episodes of social interactions, in comparison to NH. Warm-ED had no comparable effect on the rats' social behaviour. These findings indicate that ED under ambient conditions that constitute severe thermal stress for rat pups leads to development of reduced social motivation in adulthood. PMID:15582117

  11. Testosterone reduces cumulative burying in female Wistar rats with minimal participation of estradiol.

    PubMed

    Gutiérrez-García, Ana G; Contreras, Carlos M; Vásquez-Hernández, Diana I; Molina-Jiménez, Tania; Jacome-Jacome, Emma

    2009-10-01

    Testosterone exerts anxiolytic effects, but the participation of its aromatase metabolic product estradiol is controversial. Therefore, we used the defensive burying paradigm in female Wistar rats to explore testosterone's (1.0 mg/rat, s.c.) interactions with picrotoxin (a noncompetitive gamma-aminobutyric acid-A receptor [GABA(A)] antagonist; 1.0 mg/kg, i.p.), formestane (an aromatase inhibitor; 3.0 mg/rat, s.c.), and tamoxifen (an estrogen receptor-beta antagonist; 1.0 mg/kg, s.c.). Serum levels of testosterone, estradiol, and progesterone were determined in the same rats. Burying latency and locomotion did not significantly change. Systemic testosterone administration enhanced serum testosterone and estradiol levels and reduced defensive burying. This reduction in total burying was blocked by pretreatment with picrotoxin and tamoxifen, but not formestane. We conclude that testosterone produced anxiolytic-like effects in female rats that were mediated by actions at the GABA(A) receptor, with participation of the estradiol receptor-beta, rather than estradiol aromatization. PMID:19520107

  12. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model.

    PubMed

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang; Wu, Shengli

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200-300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

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

    PubMed

    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

  14. 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

  15. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. PMID:25138717

  16. Exposure to sucrose during periods of withdrawal does not reduce cocaine-seeking behavior in rats

    PubMed Central

    Nicolas, Céline; Lafay-Chebassier, Claire; Solinas, Marcello

    2016-01-01

    Concomitant access to drugs of abuse and alternative rewards such as sucrose has been shown to decrease addiction-related behaviors in animals. Here we investigated whether access to sucrose during abstinence in contexts that are temporally and physically distinct from drug-related contexts could reduce subsequent drug seeking. In addition, we investigated whether a history of cocaine self-administration would alter the rewarding effects of sucrose. Rats self-administered cocaine for ten sessions, while yoked-saline rats received only saline injections, and then we subjected them to a 30-day withdrawal period during which they had access to water and sucrose continuously or intermittently according to a schedule that induces binge-drinking behavior. At the end of the withdrawal period, rats were tested for cocaine seeking behavior during a single 6 h session. We found that exposure to cocaine increased sucrose consumption only when rats had intermittent access to sucrose, but exposure to sucrose did not alter drug seeking regardless of the schedule of access. These results suggest that exposure to cocaine cross-sensitizes to the rewarding effects of sucrose, but exposure to sucrose during abstinence, temporally and physically distinct from drug-related environments, does not to reduce drug seeking. PMID:26997496

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

    PubMed

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

    2015-02-01

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

  18. A simple method for reducing autotomy in rats after peripheral nerve lesions.

    PubMed

    Sporel-Ozakat, R E; Edwards, P M; Hepgul, K T; Savas, A; Gispen, W H

    1991-02-01

    Experiments using peripheral nerve lesions (crush or transection) in rats to study repair processes are hampered by the tendency for the animals to attack the limb in which the peripheral nerves are damaged (autotomy). In this paper we describe a simple method which significantly reduces the incidence of autotomy after peripheral nerve lesions. The method consists of painting the hind paws of operated rats with a commercially available non-toxic lotion, which is used to discourage nail-biting and thumb-sucking in humans. Although the method is not absolute, it was extremely beneficial in our experiments, since the number of animals that had to be taken out of the experiment due to severe autotomy was greatly reduced. We believe that this method may prove to be as beneficial to other investigators who are using experimental peripheral nerve lesions to study the regenerative aspects of the nervous system. PMID:2062121

  19. Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats.

    PubMed

    Pelloux, Yann; Dilleen, Ruth; Economidou, Daina; Theobald, David; Everitt, Barry J

    2012-10-01

    Whereas the majority of cocaine users quit as they experience the negative consequences of drug use, some lose control over their drug taking and compulsively seek drugs. We report that 20% of rats compulsively seek cocaine despite intermittent negative outcomes after escalating their cocaine self-administration. This compulsive subgroup showed marked reductions in forebrain serotonin utilization; increasing serotonin transmission reduced their compulsive cocaine seeking. Depleting forebrain serotonin induced compulsive cocaine seeking in rats with a limited cocaine taking history; this was reversed by systemic treatment with a 5-hydroxytryptamine (5-HT2C) receptor agonist and mimicked by systemic treatment with a 5-HT2C receptor antagonist in intact animals. These results indicate the causal involvement of reduced serotoninergic transmission in the emergence of compulsive drug seeking after a long cocaine-taking history. PMID:22763621

  20. Morphologic radiographic study of the proximal sesamoid bones of the forelimb in thoroughbred racehorses in training.

    PubMed

    Beccati, F; Gialletti, R; Giontella, A; Davanzo, S; Di Meo, A; Pepe, M

    2014-10-01

    The aim of this study was to identify differences in bone shape (height and width) of proximal sesamoid bones (PSB) in 2-year-old Thoroughbred racehorses in training. Dorsal 15° proximal-palmarodistal oblique images of each metacarpophalangeal joint were acquired before the horses started training and at 1 year after the start of exercise and racing. There were no changes in height and width of PSBs induced by training. There was a significant difference of height and width between medial and lateral PSBs. In both forelimbs, the medial PSB was significantly wider and shorter than the lateral PSB. The medial PSB of the right forelimb was significantly wider than that of the left forelimb. These results might explain some limb predilection for fracture of PSBs. The difference in strain pattern between medial and lateral PSBs in different loading conditions needs to be investigated. PMID:23796007

  1. 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

  2. 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

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

    PubMed

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

    2012-12-15

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

  4. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause

    PubMed Central

    2013-01-01

    Background The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. BMSCs and GCs were isolated from rats. GCs were separated into one of the following three groups: an untreated control group (control), a cisplatin (5 mg/L) treatment group (cisplatin), and group co-cultured with BMSCs and treated with cisplatin (BMSC). GC apoptosis was analyzed by annexin V staining and real-time PCR analysis for apoptosis-related genes. The effect of BMSCs was also determined in 9 to 10 month-old perimenopausal rats that were separated into the following groups: saline control, BMSC transplantation (1–2 × 106 cells), and estrogen treatment (0.158 mg/kg/d) groups. A young group consisting of 3 to 4 month-old rats that were treated with saline was also evaluated as a control. After 1 and 3 months, GC apoptosis was evaluated by TUNEL analysis. Results Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). Conclusions BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs. PMID:23510080

  5. Functional morphology of the forelimb of living and extinct tree-kangaroos (Marsupialia: Macropodidae).

    PubMed

    Warburton, Natalie M; Harvey, Kathryn J; Prideaux, Gavin J; O'Shea, James E

    2011-10-01

    Tree-kangaroos are a unique group of arboreal marsupials that evolved from terrestrial ancestors. The recent discovery of well-preserved specimens of extinct tree-kangaroo species (genus Bohra) within Pleistocene cave deposits of south-central Australia provides a unique opportunity to examine adaptive evolution of tree-kangaroos. Here, we provide the first detailed description of the functional anatomy of the forelimb, a central component of the locomotor complex, in the extant Dendrolagus lumholtzi, and compare its structure and function with representatives of other extant marsupial families. Several features were interpreted as adaptations for coping with a discontinuous, uneven and three-dimensional arboreal substrate through enhanced muscular strength and dexterity for propulsion, grasping, and gripping with the forelimbs. The forelimb musculoskeletal anatomy of Dendrolagus differed from terrestrial kangaroos in the following principal ways: a stronger emphasis on the development of muscles groups responsible for adduction, grasping, and gripping; the enlargement of muscles that retract the humerus; and modified shape of the scapula and bony articulations of the forelimb bones to allow improved mobility. Many of these attributes are convergent with other arboreal marsupials. Tree-kangaroos, however, still retain the characteristic bauplan of their terrestrial ancestors, particularly with regard to skeletal morphology, and the muscular anatomy of the forelimb highlights a basic conservatism within the group. In many instances, the skeletal remains of Bohra have similar features to Dendrolagus that suggest adaptations to an arboreal habit. Despite the irony of their retrieval from deposits of the Nullarbor "Treeless" Plain, forelimb morphology clearly shows that the species of Bohra were well adapted to an arboreal habitat. PMID:21630322

  6. Intrajejunal infusion of 2-monoacylglycerol reduced food intake without inducing diarrhea in rats.

    PubMed

    Okuma, Chihiro; Ohta, Takeshi; Ito, Makoto; Tadaki, Hironobu; Oda, Tomohiro; Kume, Shinichi; Nishiu, Jun; Kakutani, Makoto

    2016-02-01

    Some nutrients, such as carbohydrate, fat and protein, are known to stimulate satiety. However, the effect of sn-2-monoacylglycerol (2-MG), one of the digestive products of triglycerides, on food intake is still unclear. In the present study, the effects of 2-MG on food intake and diarrhea were evaluated and compared with long-chain fatty acid (LCFA) in rats by intrajejunal infusion. Intrajejunal infusion of 2-MG reduced food intake. In addition, 2-MG did not induce diarrhea at the condition that it comparably reduced food intake as compared with LCFA. These results suggest that 2-MG stimulates satiety without inducing diarrhea, different from LCFA. PMID:26883454

  7. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    PubMed

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients. PMID:26834859

  8. Spent turmeric reduces fat mass in rats fed a high-fat diet.

    PubMed

    Han, Kyu-Ho; Lee, Chang-Hyun; Kinoshita, Mikio; Oh, Chan-Ho; Shimada, Ken-Ichiro; Fukushima, Michihiro

    2016-04-20

    Indigestible carbohydrates may improve obesity. Spent turmeric contains high levels of dietary fibre and resistant starch (RS), which have fermentation potential in vitro. We hypothesised that indigestible carbohydrates in spent turmeric might prevent obesity development. In the first study, rats were administered 10% turmeric powder (TP) or spent turmeric powder (STP) in a high-fat (HF) diet for 28 d. In the second study, rats were fed 10% STP in a HF diet with or without antibiotics for 15 d. In the third study, rats were treated with a STP-containing suspension. In study 1, the TP and STP diet increased the caecal short-chain fatty acid (SCFA) content compared to that of a control diet. The lower energy intake in the TP and STP group was strongly related to the decrease in visceral fat weight. In study 2, after caecal fermentation suppression with antibiotics, STP treatment decreased the visceral fat mass. In study 3, the plasma glucose levels and incremental area under the curve (AUC) after ingestion of a STP-containing suspension were lower than those after ingestion of suspension alone. These findings suggest the reduction of carbohydrate absorption during the gastrointestinal passage after TP and STP treatment. Our data indicate that the reduced obesity development in rats fed a HF diet may be attributed to the low metabolisable energy density of carbohydrates in the spent turmeric, independent of SCFA-mediated factors. PMID:26583652

  9. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  10. Oxygen toxicity is reduced by acetylcholinesterase inhibition in the developing rat brain.

    PubMed

    Sifringer, Marco; Bendix, Ivo; von Haefen, Clarissa; Endesfelder, Stefanie; Kalb, Alexander; Bührer, Christoph; Felderhoff-Mueser, Ursula; Spies, Claudia D

    2013-01-01

    The cholinergic anti-inflammatory pathway is a neural mechanism that suppresses the innate inflammatory response and controls inflammation employing acetylcholine as the key endogenous mediator. In this study, we investigated the effects of the cholinergic agonists, physostigmine and donepezil, on neurodegeneration, inflammation and oxidative stress during oxygen toxicity in the developing rat brain. The aim of this study was to investigate the level of neurodegeneration, expression of proinflammatory cytokines, glutathione and lipid peroxidation after hyperoxia and treatment with the acetylcholinesterase (AChE) inhibitors, physostigmine and donepezil in the brain of neonatal rats. Six-day-old Wistar rats were exposed to 80% oxygen for 12-24 h and received 100 μg/kg physostigmine or 200 μg/kg donepezil intraperitoneally. Sex-matched littermates kept in room air and injected with normal saline, physostigmine or donepezil served as controls. Treatment with both inhibitors significantly reduced hyperoxia-triggered activity of AChE, neural cell death and the upregulation of the proinflammatory cytokines IL-1β and TNF-α in the immature rat brain on the mRNA and protein level. In parallel, hyperoxia-induced oxidative stress was reduced by concomitant physostigmine and donepezil administration, as shown by an increased reduced/oxidized glutathione ratio and attenuated malondialdehyde levels, as a sign of lipid peroxidation. Our results suggest that a single treatment with AChE inhibitors at the beginning of hyperoxia attenuated the detrimental effects of oxygen toxicity in the developing brain and may pave the way for AChE inhibitors, which are currently used for the treatment of Alzheimer's disease, as potential candidates for adjunctive neuroprotective therapies to the immature brain. PMID:23445753

  11. Protective effects of drag-reducing polymers on ischemic reperfusion injury of isolated rat heart.

    PubMed

    Hu, Feng; Wang, Yali; Gong, Kaizheng; Ge, Gaoyuan; Cao, Mingqiang; Zhao, Pei; Sun, Xiaoning; Zhang, Zhengang

    2016-01-01

    Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on ischemic reperfusion (I/R) injury of isolated rat hearts. Experiments were performed on isolated rat hearts subjected to 30 min of ischemia followed by 90 min of reperfusion in Langendorff preparations. Adult Wistar rats were divided into the following five groups: control group, I/R group, group III (I/R and 2×10(-7)  g/ml PEO reperfusion), group IV (I/R and 1×10(-6)  g/ml PEO reperfusion), and group V (I/R and 5×10(-6)  g/ml PEO reperfusion). Left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of ventricular pressure increase and decrease ( ± dp/dtmax), heart rate (HR) and coronary flow were measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity and coronary flow, myocardial infarction size and cardiomyocytes apoptosis were also assayed. Our results showed that PEO decreased LVEDP and increased LVSP, ± dP/dtmax in group IV and group V compared with the I/R group (all P <  0.05). The coronary flow significantly increased and the activities of LDH and CK in the coronary flow significantly decreased in group IV and group V compared with those in the I/R group (all P <  0.05). Cell apoptosis and myocardial infarction size were reduced in group IV and group V compared with the I/R group (all P <  0.05). Collectively, these results suggested that DRPs had a protective effect on cardiac I/R injury of isolated rat hearts and it may offer a new potential approach for the treatment of acute ischemic heart diseases. PMID:25633566

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

    PubMed

    Diogo, Rui; Molnar, Julia

    2014-06-01

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

  13. Aged Male Rats Regenerate Cortical Bone with Reduced Osteocyte Density and Reduced Secretion of Nitric Oxide After Mechanical Stimulation

    PubMed Central

    Tayim, Riyad J.; McElderry, John-David; Morris, Michael D.; Goldstein, Steven A.

    2016-01-01

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

  14. Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats.

    PubMed

    Hao, Fan; Gu, Ying; Tan, Xing; Deng, Yu; Wu, Zhao-Tang; Xu, Ming-Juan; Wang, Wei-Zhong

    2016-01-01

    Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause. PMID:26640612

  15. Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

    PubMed

    Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

    2014-03-21

    Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. PMID:24468273

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

    PubMed Central

    Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

    2012-01-01

    AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

  17. Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats

    PubMed Central

    Hao, Fan; Gu, Ying; Tan, Xing; Deng, Yu; Wu, Zhao-Tang; Xu, Ming-Juan; Wang, Wei-Zhong

    2016-01-01

    Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause. PMID:26640612

  18. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    PubMed Central

    Ropelle, Eduardo R; Pauli, José R; Prada, Patrícia; Cintra, Dennys E; Rocha, Guilherme Z; Moraes, Juliana C; Frederico, Marisa J S; da Luz, Gabrielle; Pinho, Ricardo A; Carvalheira, José B C; Velloso, Licio A; Saad, Mario A; De Souza, Cláudio T

    2009-01-01

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity. PMID:19332486

  19. Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice.

    PubMed

    Qinna, Nidal A; Ismail, Obbei A; Alhussainy, Tawfiq M; Idkaidek, Nasir M; Arafat, Tawfiq A

    2016-04-01

    The aim of the current investigation was to assess the ability GFJ to modulate the pharmacokinetic profile of paracetamol following single or repeated administrations of GFJ in Sprague-Dawley rats. Diclofenac and carbamazepine were both used as positive controls. Rats received single GFJ or single distilled water doses or pretreated with three doses of GFJ prior to test drug administration. Blood samples were collected, processed and analyzed using validated HPLC methods, and pharmacokinetic data were constructed for each group. Increase in the bioavailability of both diclofenac and carbamazepine following multiple GFJ ingestion was revealed. Conversely, the bioavailability of paracetamol was significantly reduced following multiple GFJ administration. The percentage of reduction in the C max and AUC of paracetamol were calculated as 31 and 51 %, respectively, compared to none-GFJ-treated control (P < 0.05). The T max was not essentially changed. In conclusion, frequent administration of GFJ was confirmed to modulate the pharmacokinetics of paracetamol in rats by reducing its bioavailability. Meanwhile, it may be advisable not to ingest large amounts of GFJ along with paracetamol to avoid a possible potential loss of the efficacy. PMID:25547640

  20. 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

  1. Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.

    PubMed

    de la Garza, Ana Laura; Etxeberria, Usune; Haslberger, Alexander; Aumueller, Eva; Martínez, J Alfredo; Milagro, Fermín I

    2015-08-01

    Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats. PMID:25599391

  2. Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

    PubMed Central

    Wu, Wen-shiann; Chou, Ming-ting; Chao, Chien-ming; Chang, Chen-kuei; Lin, Mao-tsun; Chang, Ching-ping

    2012-01-01

    Aim: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats. Methods: Heatstroke was induced by exposing anesthetized rats to heat stress (36 °C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 °C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity. The concentrations of tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide (NO) level was determined by Griess method. The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA). Results: Melatonin (1 and 5 mg/kg) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury, including edema, neutrophil infiltration, and hemorrhage scores; (iv) down-regulated exudate volume, BALF PMN cell number, and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1β, and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase. Conclusion: Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury. PMID:22609835

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

    PubMed Central

    2012-01-01

    Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642

  4. 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

  5. Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in rats with pulmonary hypertension.

    PubMed

    Liles, John T; Hoyer, Kirsten; Oliver, Jason; Chi, Liguo; Dhalla, Arvinder K; Belardinelli, Luiz

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right ventricular (RV) failure and death. During disease progression, structural and electrical remodeling of the right ventricle impairs pump function, creates proarrhythmic substrates, and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in patients with PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has cardioprotective effects in experimental and clinical settings of left-sided heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. We therefore hypothesized that RAN could reduce the maladaptive structural and electrical remodeling of the right ventricle and could prevent triggered ventricular arrhythmias in the monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental settings, chronic RAN treatment reduced electrical heterogeneity (right ventricular-left ventricular action potential duration dispersion), shortened heart-rate corrected QT intervals in the right ventricle, and normalized RV dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular hypertrophy, reduced circulating levels of B-type natriuretic peptide, and decreased the expression of fibrotic markers. In addition, the acute administration of RAN prevented isoproterenol-induced ventricular tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats with established PAH. These results support the notion that RAN can improve the electrical and functional properties of the right ventricle, highlighting its potential benefits in the setting of RV impairment. PMID:25770134

  6. TEMPONE reduces renal dysfunction and injury mediated by oxidative stress of the rat kidney.

    PubMed

    Patel, Nimesh S A; Chatterjee, Prabal K; Chatterjee, Bristi E; Cuzzocrea, Salvatore; Serraino, Ivana; Brown, Paul A J; Stewart, Keith N; Mota-Filipe, Helder; Thiemermann, Christoph

    2002-12-01

    Here we investigate the effects of the stable, water-soluble nitroxyl radical, TEMPONE, on renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the rat kidney in vivo. TEMPONE significantly improved both glomerular and tubular function (serum urea, creatinine, creatinine clearance, and fractional excretion of Na(+)) in a dose-dependent manner and significantly attenuated the reperfusion-injury associated with I/R (urinary N-acetyl-beta-D-glucosaminidase, aspartate aminotransferase, assessment of renal histology). TEMPONE also markedly reduced the immunohistochemical evidence of the formation of nitrotyrosine and poly(ADP-ribose), indicating reduction of nitrosative and oxidative stress, respectively. The latter was reflected in vitro, where TEMPONE significantly reduced cellular injury of primary cultures of rat renal proximal tubular (PT) cells caused by hydrogen peroxide in a dose-dependent manner. Importantly, in contrast to its in vivo metabolite TEMPOL (which also provided protective effects against renal I/R and oxidative stress of PT cells), TEMPONE reduced renal dysfunction and injury without causing a significant reduction in blood pressure upon administration. These results suggest, for the first time, that TEMPONE can reduce the renal dysfunction and injury caused by I/R and the injury caused to PT cells by oxidative stress without producing the adverse cardiovascular effects observed when using other nitroxyl radicals. PMID:12446215

  7. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model.

    PubMed

    Chen, C H; Manaenko, A; Zhan, Y; Liu, W W; Ostrowki, R P; Tang, J; Zhang, J H

    2010-08-11

    Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested the effect of hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague-Dawley rats (n=72) were divided into the following groups: sham; sham treated with hydrogen gas (H(2)); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H(2) (MCAO+H(2)). All rats received an injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 h during reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluated by measuring the level of 8 Hydroxyguanosine (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), and matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after ischemia. We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen was accompanied by a reduction of the expression of 8OHG, HNE, and nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500+/-32.51 to 366+/-68.22 mg/dl at 4 h after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occludin, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation. PMID:20423721

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

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2014-12-01

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

  9. Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2015-11-01

    Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine. PMID:26162424

  10. Hydrogen Gas Reduced Acute Hyperglycemia-Enhanced Hemorrhagic Transformation in a Focal Ischemia Rat Model

    PubMed Central

    CHEN, C.H.; ANATOL, M.; ZHAN, Y.; LIU, W.W.; OSTROWKI, R.P.; TANG, JIPING; ZHANG, J. H.

    2010-01-01

    Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague–Dawley rats (n=72) were divided into the following groups: sham; sham treated with hydrogen gas (H2); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H2 (MCAO+H2). All the rats received an injection of 50% dextrose (6ml/kg intraperitoneally) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 hr during reperfusion. We measured the level of blood glucose at 0 hr, 0.5 hr, 4 hr, and 6 hr after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluating by the level of 8OHG, HNE and nitrotyrosine), MMP-2/MMP-9 activity were measured at 24 hr after ischemia. We found that hydrogen inhalation for 2 hr reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen is accompanied by a reduction of the expressions of 8OHG, HNE, nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500±32.51 to 366±68.22 mg/dl at 4 hr after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occluding, collagen IV or AQP4. In conclusion, hydrogen gas reduced the infarction, hemorrhagic transformation, and improved neurological functions in rat. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation. PMID:20423721

  11. 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)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ 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-γ] 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-1α/β 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

  12. A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats.

    PubMed

    Lorrai, Irene; Piga, Valentina; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola

    2016-01-01

    Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a "reinstatement" procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding - being unreinforced - diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40-45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752

  13. A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats

    PubMed Central

    Lorrai, Irene; Piga, Valentina; Carai, Mauro A. M.; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola

    2016-01-01

    Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752

  14. 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

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

    PubMed

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

    2012-01-01

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

  16. Scapular Morphology and Forelimb Use during Foraging in Four Sympatric Cercopithecids.

    PubMed

    Dunham, Noah T; Kane, Erin E; McGraw, W Scott

    2015-01-01

    Most investigations of primate scapular morphology use differences in locomotion to explain variation; less is known about how scapular geometry covaries with nonlocomotor behavior. We examined forelimb use during foraging in 4 cercopithecids ranging throughout the Ivory Coast's Tai Forest. During 5-min feeding bouts, we recorded the frequency individuals of Piliocolobus badius, Colobus polykomos, Cercocebus atys and Cercopithecus diana performed 5 forelimb behaviors involved in the acquisition and introduction of food to the oral cavity. Scapulae from these populations were examined to determine whether differences in forelimb use were reflected in features known to correspond with varying degrees of arm flexion, abduction and elevation. Our results reveal that the species differ markedly in forelimb use and that these differences are interpretable via their scapular morphology. For example, P. badius engages in more frequent flexion, abduction and elevation of the arm above the head relative to C. polykomos, and red colobus scapulae are longer craniocaudally and have larger, more cranially directed supraspinous fossae than those of closely related black-and-white colobus. Our attempt to explore how nonlocomotor behavior covaries with skeletal morphology should provide for more informed interpretations of the primate fossil record. PMID:26745141

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

    PubMed

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

    2013-12-01

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

  18. 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

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

    PubMed Central

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

    2013-01-01

    BACKGROUND AND PURPOSE We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. EXPERIMENTAL APPROACH We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). KEY RESULTS In rats, THCA (0.05 and/or 0.5 mg·kg−1) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg−1) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg−1) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. CONCLUSIONS AND IMPLICATIONS THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting. PMID:23889598

  20. 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 PPARα (peroxisome proliferator–activated receptor α) 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 PPARα 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 PPARα-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

  1. The scaling of postcranial muscles in cats (Felidae) I: forelimb, cervical, and thoracic muscles.

    PubMed

    Cuff, Andrew R; Sparkes, Emily L; Randau, Marcela; Pierce, Stephanie E; Kitchener, Andrew C; Goswami, Anjali; Hutchinson, John R

    2016-07-01

    The body masses of cats (Mammalia, Carnivora, Felidae) span a ~300-fold range from the smallest to largest species. Despite this range, felid musculoskeletal anatomy remains remarkably conservative, including the maintenance of a crouched limb posture at unusually large sizes. The forelimbs in felids are important for body support and other aspects of locomotion, as well as climbing and prey capture, with the assistance of the vertebral (and hindlimb) muscles. Here, we examine the scaling of the anterior postcranial musculature across felids to assess scaling patterns between different species spanning the range of felid body sizes. The muscle architecture (lengths and masses of the muscle-tendon unit components) for the forelimb, cervical and thoracic muscles was quantified to analyse how the muscles scale with body mass. Our results demonstrate that physiological cross-sectional areas of the forelimb muscles scale positively with increasing body mass (i.e. becoming relatively larger). Many significantly allometric variables pertain to shoulder support, whereas the rest of the limb muscles become relatively weaker in larger felid species. However, when phylogenetic relationships were corrected for, most of these significant relationships disappeared, leaving no significantly allometric muscle metrics. The majority of cervical and thoracic muscle metrics are not significantly allometric, despite there being many allometric skeletal elements in these regions. When forelimb muscle data were considered in isolation or in combination with those of the vertebral muscles in principal components analyses and MANOVAs, there was no significant discrimination among species by either size or locomotory mode. Our results support the inference that larger felid species have relatively weaker anterior postcranial musculature compared with smaller species, due to an absence of significant positive allometry of forelimb or vertebral muscle architecture. This difference in strength

  2. The lateral reticular nucleus; integration of descending and ascending systems regulating voluntary forelimb movements

    PubMed Central

    Alstermark, Bror; Ekerot, Carl-Fredrik

    2015-01-01

    Cerebellar control of movements is dependent on mossy fiber input conveying information about sensory and premotor activity in the spinal cord. While much is known about spino-cerebellar systems, which provide the cerebellum with detailed sensory information, much less is known about systems conveying motor information. Individual motoneurones do not have projections to spino-cerebellar neurons. Instead, the fastest route is from last order spinal interneurons. In order to identify the networks that convey ascending premotor information from last order interneurons, we have focused on the lateral reticular nucleus (LRN), which provides the major mossy fiber input to cerebellum from spinal interneuronal systems. Three spinal ascending systems to the LRN have been investigated: the C3-C4 propriospinal neurones (PNs), the ipsilateral forelimb tract (iFT) and the bilateral ventral flexor reflex tract (bVFRT). Voluntary forelimb movements involve reaching and grasping together with necessary postural adjustments and each of these three interneuronal systems likely contribute to specific aspects of forelimb motor control. It has been demonstrated that the command for reaching can be mediated via C3-C4 PNs, while the command for grasping is conveyed via segmental interneurons in the forelimb segments. Our results reveal convergence of ascending projections from all three interneuronal systems in the LRN, producing distinct combinations of excitation and inhibition. We have also identified a separate descending control of LRN neurons exerted via a subgroup of cortico-reticular neurones. The LRN projections to the deep cerebellar nuclei exert a direct excitatory effect on descending motor pathways via the reticulospinal, vestibulospinal, and other supraspinal tracts, and might play a key role in cerebellar motor control. Our results support the hypothesis that the LRN provides the cerebellum with highly integrated information, enabling cerebellar control of complex forelimb

  3. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  4. 2-methoxycinnamaldehyde reduces IL-1beta-induced prostaglandin production in rat cerebral endothelial cells.

    PubMed

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

    2006-11-01

    Prostaglandin E2 (PGE2) works as a common final mediator of the febrile. Guizhi-Tang, one of the most famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions, was previously reported to reduce the production of PGE 2 in rats. 2-Methoxycinnamaldehyde is a principle compound isolated from Guizhi-Tang. The aim of the present study was to investigate the effects of 2-methoxycinnamaldehyde on PGE2 production of rat cerebral endothelial cells (CECs). 2-Methoxycinnamaldehyde dose-dependently inhibited interleukin (IL)-1beta-induced PGE2 production in CECs with IC50 values of 174 microM. IL-1beta stimulation increased the protein, activity and mRNA expression of cyclooxygenase (COX)-2 but not COX-1. 2-Methoxycinnamaldehyde reduced IL-1beta-induced protein and activity of COX-2, but did not influence the COX-2 mRNA expression. Our results show that prostaglandin production in CECs during stimulated conditions is sensitive to inhibition by 2-methoxycinnamaldehyde and suggest that 2-methoxycinnamaldehyde may reduce COX-2 protein level and activity but not COX-2 mRNA. PMID:17077517

  5. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    PubMed

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  6. BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.

    PubMed

    Veljaca, M; Lesch, C A; Pllana, R; Sanchez, B; Chan, K; Guglietta, A

    1995-01-01

    The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is characterized by areas of necrosis surrounded by areas of acute inflammation. The damage is associated with high myeloperoxidase (MPO) activity, mainly as a reflection of neutrophilic infiltration into the damaged tissue. In this study, 1 hr before a single intracolonic administration of 50 mg/kg of TNBS in 50% ethanol, the animals were treated with one of the following doses of BPC-15: 0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10 nmol/kg administered intracolonically. The animals were sacrificed 3 days later and the extent of colonic necrosis and hyperemia was measured with an image analyzer. The i.p. administration of BPC-15 significantly reduced the extent of TNBS-induced colonic damage in a dose-dependent manner. This was associated with a statistically significant and dose-dependent reduction in colonic tissue MPO activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15 did not significantly reduce either the extent of the colonic damage or the increase in MPO activity induced by TNBS. In conclusion, this study showed that i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats. PMID:7815358

  7. Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats.

    PubMed

    Aoyama, Kenjiro; Barnes, Jesse; Koerber, Jon; Glueck, Edwin; Dorsey, Kylan; Eaton, Laura; Grimm, Jeffrey W

    2016-10-01

    Conditioned cues can elicit drug- and sucrose-seeking behaviors that have been shown to depend on dopamine (DA) D1 receptors. If DAD1 receptors are also involved in seeking behavior in general, blocking these receptors should reduce seeking behavior for a non-caloric, non-drug of abuse reinforcer such as saccharin. Forty-six male Long-Evans rats lever pressed for 0.3% saccharin solution 1 h/day for 10 days. A lever response also activated a tone plus a white stimulus light. This compound stimulus lasted for 5 s. After 1 day of forced abstinence, rats received systemic (0, 1, or 10 μg/kg IP; n = 15-16 per group) injections of SCH 23390 15 min prior to extinction testing. Systemic SCH 23390 reduced saccharin seeking evidenced by a significant reduction in active lever responding and a significant reduction in the number of active lever-contingent deliveries of the tone + light cue following pretreatment with 10 μg/kg SCH 23390. The slope of responding across the Test session in this group was also significantly steeper, indicating that SCH 23390 may have reduced the persistence of saccharin seeking. The results indicate that DAD1 receptors are involved in saccharin seeking and generalize the previously demonstrated anti-seeking effects of DAD1 antagonism to a non-caloric, non-drug of abuse reinforcer. PMID:27179937

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  9. Propofol anesthesia reduces Lempel-Ziv complexity of spontaneous brain activity in rats.

    PubMed

    Hudetz, Anthony G; Liu, Xiping; Pillay, Siveshigan; Boly, Melanie; Tononi, Giulio

    2016-08-15

    Consciousness is thought to scale with brain complexity, and it may be diminished in anesthesia. Lempel-Ziv complexity (LZC) of field potentials has been shown to be a promising measure of the level of consciousness in anesthetized human subjects, neurological patients, and across the sleep-wake states in rats. Whether this relationship holds for intrinsic networks obtained by functional brain imaging has not been tested. To fill this gap of knowledge, we estimated LZC from large-scale dynamic analysis of functional magnetic resonance images (fMRI) in conscious sedated and unconscious anesthetized rats. Blood oxygen dependent (BOLD) signals were obtained from 30-min whole-brain resting-state scans while the anesthetic propofol was infused intravenously at constant infusion rates of 20mg/kg/h (conscious sedated) and 40mg/kg/h (unconscious). Dynamic brain networks were defined at voxel level by sliding window analysis of regional homogeneity (ReHo) of the BOLD signal. From scans performed at low to high propofol dose, the LZC was significantly reduced by 110%. The results suggest that the difference in LZC between conscious sedated and anesthetized unconscious subjects is conserved in rats and this effect is detectable in large-scale brain network obtained from fMRI. PMID:27291459

  10. Cryotherapy reduces skeletal muscle damage after ischemia/reperfusion in rats

    PubMed Central

    Puntel, Gustavo O; Carvalho, Nélson R; Dobrachinski, Fernando; Salgueiro, Andréia C F; Puntel, Robson L; Folmer, Vanderlei; Barbosa, Nilda B V; Royes, Luiz F F; Rocha, João Batista T; Soares, Félix A A

    2013-01-01

    The aim of this study was to analyze the effects of cryotherapy on the biochemical and morphological changes in ischemic and reperfused (I/R) gastrocnemius muscle of rats. Forty male Wistar rats were divided into control and I/R groups, and divided based on whether or not the rats were submitted to cryotherapy. Following the reperfusion period, biochemical and morphological analyses were performed. Following cryotherapy, a reduction in thiobarbituric acid-reactive substances and dichlorofluorescein oxidation levels were observed in I/R muscle. Cryotherapy in I/R muscle also minimized effects such as decreased cellular viability, levels of non-protein thiols and calcium ATPase activity as well as increased catalase activity. Cryotherapy also limited mitochondrial dysfunction and decreased the presence of neutrophils in I/R muscle, an effect that was corroborated by reduced myeloperoxidase activity in I/R muscle treated with cryotherapy. The effects of cryotherapy are associated with a reduction in the intensity of the inflammatory response and also with a decrease in mitochondrial dysfunction. PMID:23231035

  11. Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats.

    PubMed

    Alexandrov, Andrei V; Barlinn, Kristian; Strong, Roger; Alexandrov, Anne W; Aronowski, Jaroslaw

    2011-09-01

    It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128 mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas. PMID:24323655

  12. Extended exposure to environmental cues, but not to sucrose, reduces sucrose cue reactivity in rats.

    PubMed

    Harkness, John H; Wells, Jason; Webb, Sierra; Grimm, Jeffrey W

    2016-03-01

    In the present study, we examined the effects of extinction of sucrose-predictive contextual cues and/or sucrose satiation on the expression of sucrose cue reactivity in a rat model of relapse. Context extinction was imposed by housing rats in their home cage or in the operant conditioning chamber for 17 h prior to testing. For sucrose satiation, rats were allowed unlimited access to water or sucrose for 17 h prior to testing. Cue reactivity was assessed after either one (Day 1) or 30 (Day 30) days of forced abstinence from sucrose self-administration. An abstinence-dependent increase in sucrose cue reactivity was observed in all conditions ("incubation of craving"). Context extinction dramatically reduced lever responding on both Day 1 and Day 30. Sucrose satiation had no significant effect on cue reactivity in any condition. These results demonstrate that the context in which self-administration occurs maintains a powerful influence over cue reactivity, even after extended forced abstinence. In contrast, the primary reinforcer has little control over cue reactivity. These findings highlight the important role of conditioned contextual cues in driving relapse behavior. PMID:26169836

  13. Tyrphostin AG 126 reduces intestinal ischemia-reperfusion injury in the rat.

    PubMed

    Marzocco, Stefania; Mazzon, Emanuela; Pinto, Aldo; Autore, Giuseppina; Cuzzocrea, Salvatore

    2006-02-01

    In this study, we evaluated the effect of tyrphostin AG126, a tyrosine kinase inhibitor, in the splanchnic artery occlusion (SAO) shock mediated injury. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO shocked rats developed a significant fall in mean arterial blood pressure. Ileum analysis revealed that SAO shock is characterized by a significant (P<0.01) induction in TNF-alpha and IL-1 ileum levels, while immunohistochemistry examination of necrotic ileum demonstrated a marked increase in the immunoreactivity in intracellular adhesion molecule (ICAM-1) and nitrotyrosine formation. A significant increase in myeloperoxidase activity (P<0.01) was also observed in rats subjected to ischemia-reperfusion injury. Tyrphostin AG126, given intraperitoneally 30 min before ischemia at the dose of 5 mg/kg, significantly improved mean arterial blood pressure, markedly reduced TNF-alpha and IL-1beta levels and the positive staining of ICAM-1 into the reperfused ileum. Tyrphostin AG126 significantly improved the histological status of the reperfused tissue. In conclusion, this study demonstrates that tyrphostin AG126 exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock and suggests that this tyrosine kinase inhibitor may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury. PMID:16485131

  14. The edible brown seaweed Ecklonia cava reduces hypersensitivity in postoperative and neuropathic pain models in rats.

    PubMed

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

    2014-01-01

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

  15. mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of Metabolic Syndrome

    PubMed Central

    Rovira, Jordi; Ramírez-Bajo, María Jose; Banon-Maneus, Elisenda; Moya-Rull, Daniel; Ventura-Aguiar, Pedro; Hierro-Garcia, Natalia; Lazo-Rodriguez, Marta; Revuelta, Ignacio; Torres, Armando; Oppenheimer, Federico; Campistol, Josep M.; Diekmann, Fritz

    2016-01-01

    Background Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β-cell toxicity. Methods Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, β-cell proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to analyze insulin content, insulin secretion, and gene expression. Results After 12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR. Treatment prolongation induced increase of area under the curve of IPGTT in LZR and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2 hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as well as insulin content. Insulin secretion was only affected in OZR. Islets from OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes related with insulin secretion remained unchanged or upregulated. Conclusions In conditions that require adaptive β-cell proliferation, SRL might reveal harmful effects by blocking β-cell proliferation, insulin production and secretion. These effects disappeared when removing the therapy.

  16. 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

  17. Reduced capillary density in the myocardium of uremic rats--a stereological study.

    PubMed

    Amann, K; Wiest, G; Zimmer, G; Gretz, N; Ritz, E; Mall, G

    1992-11-01

    Using stereological techniques capillaries, interstitium and myocardial fibers were analyzed in perfusion-fixed hearts of subtotally nephrectomized male Sprague-Dawley rats with uremia of 14 months duration (or their sham-operated controls). Uremic rats had higher systolic blood pressure (140 +/- 20.3 mm Hg vs. 119 +/- 6.61 mm Hg) and left ventricular weight/body weight ratio (3.37 +/- 0.09 mg/kg vs. 2.01 +/- 0.12 mg/kg) than controls, and had slight anemia (Hct 35.0 +/- 3.16% vs. 40.4 +/- 3.3%). Length density (Lv) of capillaries, that is, capillary length per unit myocardial volume, was significantly (P < 0.001) decreased in uremia (2485 +/- 264 mm/mm3 vs. 3329 +/- 194 mm/mm3) versus controls. In parallel, surface density and volume density of the capillary lumina were also reduced (7.95 +/- 1.69 cm3/cm3 vs. 11.4 +/- 1.8 cm3/cm3) in the uremic rats. We conclude that in experimental uremia, cardiac hypertrophy is not accompanied by a commensurate increase in capillaries. PMID:1453595

  18. Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

    PubMed

    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 (1)H 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

  19. Intranasal leptin reduces appetite and induces weight loss in rats with diet-induced obesity (DIO).

    PubMed

    Schulz, Carla; Paulus, Kerstin; Jöhren, Olaf; Lehnert, Hendrik

    2012-01-01

    Resistance to brain-mediated effects of leptin is a characteristic feature of obesity, resulting from alterations in leptin receptor signaling in hypothalamic neurons and/or transport across the blood-brain-barrier. We have shown previously, that the latter can be circumvented by intranasal (i.n.) application of leptin in lean rats. This prompted us to test i.n. leptin in animals with diet-induced obesity (DIO) as a basis for future human administration. DIO was induced in male Wistar rats by feeding a cafeteria diet for 25 or 32 wk, respectively. Consecutively, these DIO animals (seven to eight per treatment) and standard diet rats (lean) (14-15 per treatment, matched for age and diet duration) were treated with 0.1, 0.2 mg/kg leptin, or control solution i.n. daily for 4 wk before onset of dark period. Energy intake and body weight were measured daily; blood glucose, serum insulin, and leptin were measured before and after treatment. Expression of hypothalamic neuropeptides was assessed by quantitative real-time PCR. We demonstrate, for the first time, that i.n. leptin reduces appetite and induces weight loss in DIO to the same extent as in lean rats. Our findings are supported accordingly by an altered expression pattern of anorexigenic and orexigenic neuropeptides in the hypothalamus, e.g. proopiomelanocortin, cocaine and amphetamine-related transcript, neuropeptide Y, agouti-related protein. It now appears clear that i.n. leptin is effectively acting in obese animals in the same fashion as in their lean counterparts. These findings now clearly warrant studies in humans and may open new perspectives in the treatment of obesity. PMID:22128019

  20. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    PubMed Central

    Mota, Marcelo Mendonça; da Silva, Tharciano Luiz Teixeira Braga; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos; de Oliveira, Antônio Cesar Cabral; Wichi, Rogério Brandão; Santos, Márcio Roberto Viana

    2014-01-01

    Background Resistance exercise effects on cardiovascular parameters are not consistent. Objectives The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Conclusions Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats. PMID:25120082

  1. Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

    PubMed Central

    Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

    2015-01-01

    Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the

  2. D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats.

    PubMed

    Seif, Taban; Simms, Jeffrey A; Lei, Kelly; Wegner, Scott; Bonci, Antonello; Messing, Robert O; Hopf, F Woodward

    2015-09-01

    There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at -70 mV in vitro by optogenetic stimulation of mPFC-NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs. PMID:25801502

  3. Shengmai San reduces hepatic lipids and lipid peroxidation in rats fed on a high-cholesterol diet.

    PubMed

    Yao, Hsien-Tsung; Chang, Yi-Wei; Chen, Chiung-Tong; Chiang, Meng-Tsan; Chang, Ling; Yeh, Teng-Kuang

    2008-02-28

    Shengmai San (SMS), which is comprised of the medicinal herbs of Panax ginseng C.A. Meyer, Schisandra chinensis Baill., and Ophiopogon japonicus Ker-Gawl (2:1:2)., is a traditional Chinese medicine being used for treating coronary heart disease. The aim of this study was to investigate the effects of SMS on the plasma and liver lipids, lipid peroxidation and antioxidant systems in liver and heart of cholesterol-fed rats. Rats were fed on a high-cholesterol (0.5%) diet (control group), high-cholesterol diet containing 2% SMS (2% SMS group) and 4% SMS (4% SMS group) for four weeks. The oxidative stress marker (thiobarbituric acid reactive substances, TBARS) and antioxidant defense systems including glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities in rat liver and heart were evaluated. Results showed that rats fed with SMS-containing diet had reduced the H(2)O(2)-induced erythrocytes susceptibility to hemolysis, and 4% SMS feeding rats had higher plasma GSH concentration compared to the animals fed with the control diet. However, SMS had no effect on plasma lipids (total cholesterol, triglyceride and high-density lipoprotein cholesterol) and TBARS concentration. On the other hand, rats fed with the 4% SMS diet reduced the hepatic cholesterol and triglyceride contents. Fecal bile acid excretion was significantly increased in rats fed with the SMS-containing diet. Higher hepatic GSH and lower TBARS concentrations were observed in rats fed with the 4% SMS diet compared with the rats fed with the control diet. No significant difference in activities of GSH-Px, GST and SOD was found in liver and heart after the SMS treatment. Results from this study indicate that the SMS may reduce hepatic lipids and lipid peroxidation in rats. PMID:18162350

  4. Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia- reperfusion injury★

    PubMed Central

    Zhang, Ying; Liu, Xiangrong; Yan, Feng; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2012-01-01

    Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury. PMID:25745448

  5. Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats.

    PubMed

    Hood, Suzanne; Sorge, Robert E; Stewart, Jane

    2007-03-01

    The mechanisms through which buprenorphine (BUP), a mixed opioid agonist-antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues. PMID:17346785

  6. 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

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

    PubMed Central

    Burch, Sara H

    2014-01-01

    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

  8. 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

  9. Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

    PubMed Central

    Babaee, Abdolreza; Eftekhar-Vaghefi, Seyed Hassan; Asadi-shekaari, Majid; Shahrokhi, Nader; Soltani, Samereh Dehghani; Malekpour-Afshar, Reza; Basiri, Mohsen

    2015-01-01

    Objective(s): Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis) in several models of brain injury. Secondary injury following the primary traumatic brain injury (TBI) results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis), as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline) and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg). All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP) marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P<0.05) in melatonin- treated groups (no dose dependent) compared to the vehicle group. Furthermore, based on TUNEL results, melatonin treatment considerably reduced the number of apoptotic cells (P<0.05). Conclusion: In total, the present findings suggest that melatonin treatment following TBI diminishes astrocyte reactivity and neuronal cells apoptosis in brain cortex in the rat model. PMID:26523219

  10. Yellow pea fiber improves glycemia and reduces Clostridium leptum in diet-induced obese rats.

    PubMed

    Eslinger, Amanda J; Eller, Lindsay K; Reimer, Raylene A

    2014-08-01

    Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P < .05). Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P < .05). Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P < .05). The Firmicutes/Bacteroidetes ratio was reduced with OFS, PF, and PFL when compared with PS (P < .05). Taken together, this work suggests that yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats. PMID:25156790

  11. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  12. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats.

    PubMed

    Ren, Xiaoyan; Ma, Hong; Zuo, Zhiyi

    2016-06-01

    Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues. PMID:26932203

  13. Rapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin Synthesis in Aged Rats.

    PubMed

    Scarpace, Philip J; Matheny, Michael; Strehler, Kevin Y E; Toklu, Hale Zerrin; Kirichenko, Nataliya; Carter, Christy S; Morgan, Drake; Tümer, Nihal

    2016-07-01

    This investigation examines whether a low intermittent dose of rapamycin will avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin while still decreasing body weight and adiposity in aged obese rats. Furthermore, we examined if the rapamycin-mediated decrease in serum leptin was a reflection of decreased adiposity, diminished leptin synthesis, or both. To these ends, rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old rats. Body weight, food intake, body composition, mTORC1 signaling, markers of metabolism, as well as serum leptin levels and leptin synthesis in adipose tissue were examined and compared to that following a central infusion of rapamycin. Our data suggest that the dosing schedule of rapamycin acts on peripheral targets to inhibit mTORC1 signaling, preferentially reducing adiposity and sparing lean mass in an aged model of obesity resulting in favorable outcomes on blood triglycerides, increasing lean/fat ratio, and normalizing elevated serum leptin with age. The initial mechanism underlying the rapamycin responses appears to have a peripheral action and not central. The peripheral rapamycin responses may communicate an excessive nutrients signal to the hypothalamus that triggers an anorexic response to reduce food consumption. This coupled with potential peripheral mechanism serves to decrease adiposity and synthesis of leptin. PMID:25617379

  14. Sleep deprivation reduces proliferation of cells in the dentate gyrus of the hippocampus in rats

    PubMed Central

    guzmán-marín, Ruben; Suntsova, Natalia; Stewart, Darya R; Gong, Hui; Szymusiak, Ronald; McGinty, Dennis

    2003-01-01

    The dentate gyrus (DG) of the adult hippocampus gives rise to progenitor cells, which have the potential to differentiate into neurons. To date it is not known whether sleep or sleep loss has any effect on proliferation of cells in the DG. Male rats were implanted for polysomnographic recording, and divided into treadmill sleep-deprived (SD), treadmill control (TC) and cage control (CC) groups. SD and TC rats were kept for 96 h on a treadmill that moved either for 3 s on/12 s off (SD group) or for 15 min on/60 min off (TC group) to equate total movement but permit sustained rest periods in TC animals. To label proliferating cells the thymidine analogue 5-bromo-2′-deoxyuridine (BrdU) was injected after the first 48 h of the experimental procedure in all groups (50 mg kg−1, i.p.). The percentage of time awake per day was 93.2 % in the SD group vs. 59.6 % in the TC group and 49.9 % in the CC group (P < 0.001). Stereological analysis showed that the number of BrdU-positive cells in the DG of the dorsal hippocampus was reduced by 54 % in the SD group in comparison with the TC and by 68 % in comparison with the CC group. These results suggest that sleep deprivation reduces proliferation of cells in the DG of the dorsal hippocampus. PMID:12679377

  15. Papain reduces gastric acid secretion induced by histamine and other secretagogues in anesthetized rats.

    PubMed

    Cho, C H; Han, P W

    1984-04-01

    We studied the effect of papain on rats' gastric acid secretion and found that: 1. Feeding of latex of unripe papaya fruit significantly reduced gastric acid secretion induced by methacholine; 2. Feeding of crystalline papain in doses of 3.2 mg/kg reduced gastric acid secretion induced by histamine, methacholine and tetragastrin; 3. The reduction of gastric acid secretion was observed as early as 2 hours after papain feeding, lasted up to 48 hours, and waned within 96 hours; 4. Intraperitoneal injection of papain had no effect on acid secretion. These results led us to believe tha the effect of papain on gastric acid secretion is a local one acting directly on the gastric mucosa, and this local effect of a single dose of papain is reversible, causing no permanent damage to the mucosa. PMID:6400589

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

    PubMed

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

    2015-06-01

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

  17. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

    PubMed

    Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

    2016-03-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self

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

    PubMed

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

    2008-08-01

    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 bundlesto 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 GI. 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

  19. 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

  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

  1. Reduced NOS3 phosphorylation mediates reduced NO/cGMP signaling in mesenteric arteries of deoxycorticosterone acetate-salt hypertensive rats.

    PubMed

    Sasser, Jennifer M; Sullivan, Jennifer C; Elmarakby, Ahmed A; Kemp, Bruce E; Pollock, David M; Pollock, Jennifer S

    2004-05-01

    Salt-sensitive hypertension is associated with impaired NO/cGMP signaling. We hypothesized that increased superoxide production by NADPH oxidase and altered endothelial NO synthase (NOS3) phosphorylation determine endothelial dysfunction in hypertension. Experiments tested if NO/cGMP signaling and NOS3 serine phosphorylation are decreased and NADPH oxidase activity is increased in mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt rats compared with arteries from placebo rats. Concentration response curves to phenylephrine were performed in mesenteric arteries in the presence and absence of Nomega-nitro-L-arginine (LNA) and antioxidants to determine the influence of basal NO and superoxide production on vascular tone. LNA increased phenylephrine sensitivity in arteries from placebo, but not DOCA-salt rats, regardless of antioxidant treatment. To determine basal cGMP production, mesenteric arteries were incubated with 3-isobutyl-1-methylxanthine in the presence or absence of LNA, sodium nitroprusside (SNP), antioxidants, or tetrahydrobiopterin. NOS-dependent cGMP production was reduced in arteries from DOCA-salt rats compared with arteries from placebo rats and was not restored by acute treatment with antioxidants or tetrahydrobiopterin. SNP-induced cGMP production was similar between groups as was NADPH oxidase activity, measured by lucigenin chemiluminescence, in mesenteric arteries. Expression and phosphorylation of NOS3 were examined by Western blotting. Phosphorylation of NOS3 was decreased in arteries from DOCA-salt rats compared with placebo at serine residues 1179 and 635. These findings indicate that diminished NO/cGMP signaling in mesenteric arteries from DOCA-salt rats is caused by reduced phosphorylation of NOS3 at serine 1179 and serine 635, rather than NO scavenging by superoxide. PMID:14993198

  2. 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 β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β 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 β 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

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

    PubMed

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

    2008-01-01

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

  4. Taurine Supplementation Reduces Blood Pressure and Prevents Endothelial Dysfunction and Oxidative Stress in Post-Weaning Protein-Restricted Rats

    PubMed Central

    Maia, Aline R.; Batista, Thiago M.; Victorio, Jamaira A.; Clerici, Stefano P.; Delbin, Maria A.; Carneiro, Everardo M.; Davel, Ana P.

    2014-01-01

    Introduction Taurine is a sulfur-containing amino acid that exerts protective effects on vascular function and structure in several models of cardiovascular diseases through its antioxidant and anti-inflammatory properties. Early protein malnutrition reprograms the cardiovascular system and is linked to hypertension in adulthood. This study assessed the effects of taurine supplementation in vascular alterations induced by protein restriction in post-weaning rats. Methods and Results Weaned male Wistar rats were fed normal- (12%, NP) or low-protein (6%, LP) diets for 90 days. Half of the NP and LP rats concomitantly received 2.5% taurine supplementation in the drinking water (NPT and LPT, respectively). LP rats showed elevated systolic, diastolic and mean arterial blood pressure versus NP rats; taurine supplementation partially prevented this increase. There was a reduced relaxation response to acetylcholine in isolated thoracic aortic rings from the LP group that was reversed by superoxide dismutase (SOD) or apocynin incubation. Protein expression of p47phox NADPH oxidase subunit was enhanced, whereas extracellular (EC)-SOD and endothelial nitric oxide synthase phosphorylation at Ser 1177 (p-eNOS) were reduced in aortas from LP rats. Furthermore, ROS production was enhanced while acetylcholine-induced NO release was reduced in aortas from the LP group. Taurine supplementation improved the relaxation response to acetylcholine and eNOS-derived NO production, increased EC-SOD and p-eNOS protein expression, as well as reduced ROS generation and p47phox expression in the aortas from LPT rats. LP rats showed an increased aortic wall/lumen ratio and taurine prevented this remodeling through a reduction in wall media thickness. Conclusion Our data indicate a protective role of taurine supplementation on the high blood pressure, endothelial dysfunction and vascular remodeling induced by post-weaning protein restriction. The beneficial vascular effect of taurine was

  5. Linseed dietary fibers reduce apparent digestibility of energy and fat and weight gain in growing rats.

    PubMed

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

    2013-08-01

    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

  6. 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

  7. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  8. Select forelimb muscles have evolved superfast contractile speed to support acrobatic social displays.

    PubMed

    Fuxjager, Matthew J; Goller, Franz; Dirkse, Annika; Sanin, Gloria D; Garcia, Sarah

    2016-01-01

    Many species perform rapid limb movements as part of their elaborate courtship displays. However, because muscle performance is constrained by trade-offs between contraction speed and force, it is unclear how animals evolve the ability to produce both unusually fast appendage movement and limb force needed for locomotion. To address this issue, we compare the twitch speeds of forelimb muscles in a group of volant passerine birds, which produce different courtship displays. Our results show that the two taxa that perform exceptionally fast wing displays have evolved 'superfast' contractile kinetics in their main humeral retractor muscle. By contrast, the two muscles that generate the majority of aerodynamic force for flight show unmodified contractile kinetics. Altogether, these results suggest that muscle-specific adaptations in contractile speed allow certain birds to circumvent the intrinsic trade-off between muscular speed and force, and thereby use their forelimbs for both rapid gestural displays and powered locomotion. PMID:27067379

  9. 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 μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; 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 μ-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

  10. Sodium salicylate reduces the level of GABAB receptors in the rat's inferior colliculus.

    PubMed

    Butt, S; Ashraf, F; Porter, L A; Zhang, H

    2016-03-01

    Previous studies have indicated that sodium salicylate (SS) can cause hearing abnormalities through affecting the central auditory system. In order to understand central effects of the drug, we examined how a single intraperitoneal injection of the drug changed the level of subunits of the type-B γ-aminobutyric acid receptor (GABAB receptor) in the rat's inferior colliculus (IC). Immunohistochemical and western blotting experiments were conducted three hours following a drug injection, as previous studies indicated that a tinnitus-like behavior could be reliably induced in rats within this time period. Results revealed that both subunits of the receptor, GABABR1 and GABABR2, reduced their level over the entire area of the IC. Such a reduction was observed in both cell body and neuropil regions. In contrast, no changes were observed in other brain structures such as the cerebellum. Thus, a coincidence existed between a structure-specific reduction in the level of GABAB receptor subunits in the IC and the presence of a tinnitus-like behavior. This coincidence likely suggests that a reduction in the level of GABAB receptor subunits was involved in the generation of a tinnitus-like behavior and/or used by the nervous system to restore normal hearing following application of SS. PMID:26705739

  11. Farnesoid X receptor agonist CDCA reduces blood pressure and regulates vascular tone in spontaneously hypertensive rats.

    PubMed

    Li, Chenyu; Li, Jing; Weng, Xu; Lan, Xiaofang; Chi, Xiangbo

    2015-07-01

    The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, which plays an essential role in lipid homeostasis and glucose metabolism. However, whether or not FXR can prevent rise in blood pressure remains unknown. Here, we investigate the possibility of using chenodeoxycholic acid (CDCA), a natural ligand of FXR, to attenuate elevated blood pressure in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were treated with CDCA (30 mg/kg) for 8 weeks. Compared with vehicle control, CDCA attenuated rise in blood pressure in SHR. In addition, CDCA improved vasorelaxation and diminished the contractile response to endothelin-1 (ET-1) in mesenteric arteries from SHR. CDCA also stimulated endothelial nitric oxide synthase (eNOS) expression, repressed ET-1 levels, and inhibited NF-κB activities in mesenteric arteries of the SHR. Overall, we showed that CDCA treatment reduces systolic blood pressure, improves vascular relaxation, and inhibits vasoconstriction activity in SHR. The repressed ET-1 level, the raised eNOS expression, and the ameliorated inflammation in mesenteric arteries could be responsible for the vasorelaxant and hypotensive effect of CDCA. These findings support a potential role for FXR as a regulator in vascular activities and in the development of treatment for hypertension. PMID:26188398

  12. 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 μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; 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 μ-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

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

    SciTech Connect

    Noble, E.P.; Ritchie, T. )

    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.

  14. Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats.

    PubMed

    Jawna-Zboińska, Katarzyna; Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Wawer, Adriana; Pyrzanowska, Justyna; Piechal, Agnieszka; Mirowska-Guzel, Dagmara; Widy-Tyszkiewicz, Ewa

    2016-05-01

    Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26814055

  15. Repair of a canine forelimb skin deficit by microvascular transfer of a caudal superficial epigastric flap.

    PubMed

    Lewin, G A; Smith, J H

    2010-02-01

    Extensive skin loss from the forelimb of a Border collie was repaired by a microvascular caudal superficial epigastric flap, with secondary meshing of the flap to increase coverage. The caudal superficial epigastric artery and vein were anastomosed to the brachial artery and vein. End-to-end anastomosis to the brachial artery and vein did not compromise peripheral blood flow, and no flap necrosis was observed after subsequent limited meshing of the flap. PMID:20070493

  16. 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.

  17. 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-κB ligand (receptor activator of nuclear factor-κB 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-α, interleukin (IL)-1β 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

  18. 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

  19. Reduced cell proliferation and increased apoptosis in the hippocampal formation in a rat model of Hirschsprung's disease.

    PubMed

    Xie, Dan; Croaker, G David H; Li, Jimei; Song, Zan-Min

    2016-07-01

    Hirschsprung's disease (HSCR) is a congenital malformation characterized by the absence of enteric ganglia in the distal intestine and gut obstruction. Some HSCR patients also have associated neurological symptoms. We studied a rat model of HSCR, also known as spotting lethal (sl/sl) rat, which carries a spontaneous deletion in the gene of endothelin receptor B (EDNRB) and a similar phenotype as humans with HSCR. We focused on the changes in cell proliferation and apoptosis in the hippocampal formation of the sl/sl rat. Proliferating cells in wildtype (+/+), heterozygous (+/sl) and homozygous (sl/sl) rats were labelled by intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) at postnatal day 2. The density of proliferating cells in the CA1 and CA3 regions of the hippocampus and dentate gyrus of sl/sl rats was significantly reduced compared to +/+ rats. The effect of EDNRB mutation on cell apoptosis was examined by using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling assay. This showed that the density of apoptotic cells in the hippocampal formation, particularly in the CA1 region of sl/sl rats, was significantly increased compared to +/+ rats. The expression of brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) was measured with ELISA in the hippocampal formation, but no difference was revealed between genotypes. These results suggest that EDNRB mutation reduces cell proliferation and increases apoptosis in the hippocampal formation of the sl/sl rat, but does not alter the levels of BDNF and GDNF. Our findings provide an insight into the cellular changes in the brains of HSCR patients caused by EDNRB mutation. PMID:27017960

  20. 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.

  1. Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

    PubMed

    González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

    2008-01-01

    It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage. PMID:18579343

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed Central

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

    2012-01-01

    Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either, FB1 control, FB1 + 2% NS or absolute control group. FB1 alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day−1) or placebo (1.5 g day−1) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB1 biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analyzed (n = 186) had detectable levels of FB1. Median urinary FB1 levels were significantly (p < 0.05) decreased by > 90% in the high dose NS group (3 g day−1) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB1 (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB1. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB1 is suspected to be a dietary risk factor for HCC and esophageal cancer in humans. PMID:22324939

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

    PubMed

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

    2011-05-01

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

  8. Phencyclidine (PCP) reduces the intensity of caffeine-induced convulsions in rats.

    PubMed

    Turgeon, S M; Leccese, A P

    1989-01-01

    The effects of phencyclidine (PCP) on the threshold and intensity of caffeine-induced convulsions in rats were examined. There was a dose-dependent effect of PCP on convulsion intensity with significant reduction in intensity at 4.0 and 8.0 mg/kg PCP. At 16.0 mg/kg PCP, convulsant intensity was reduced in 50% of subjects but potentiated to the point of death in the remaining 50%. PCP had no significant effect on threshold for caffeine-induced convulsions. These results suggest that PCP antagonizes caffeine-induced convulsions and further suggests that the mechanisms involved in onset of caffeine-induced convulsions and the decrease of convulsion intensity are pharmacologically dissociable. PMID:2733542

  9. Chronic treatment with epigallocatechin gallate reduces motor hyperactivity and affects in vitro tested intestinal motility of spontaneously hypertensive rats

    PubMed Central

    Potenza, Maria Assunta; Montagnani, Monica; Nacci, Carmela; De Salvia, Maria Antonietta

    2016-01-01

    Background Green tea catechins seem to contribute toward reducing body weight and fat. Objective We aimed to investigate whether chronic administration of (–)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. Design Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. Results Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05–5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1–10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG

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

    PubMed

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

    2008-03-01

    In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists on known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight-bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 min under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2h, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2mg/kg, i.p. or 30 microg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1mg/kg, i.p.) failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine, an alpha(2)-adrenergic antagonist, reduced the EA-induced analgesia in a dose-dependent manner, whereas terazosin, an alpha(1)-adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal alpha(2)-adrenoceptor mechanisms. PMID:17537577