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1

Rapid and persistent impairments of the forelimb motor representations following cervical deafferentation in rats  

PubMed Central

Skilled motor control is regulated by the convergence of somatic sensory and motor signals in brain and spinal motor circuits. Cervical deafferentation is known to diminish forelimb somatic sensory representations rapidly and to impair forelimb movements. Our focus was to determine what effect deafferentation has on the motor representations in motor cortex, knowledge of which could provide new insights into the locus of impairment following somatic sensory loss, such as after spinal cord injury or stroke. We hypothesized that somatic sensory information is important for cortical motor map topography. To investigate this we unilaterally transected the dorsal rootlets in adult rats from C4 to C8 and mapped the forelimb motor representations using intracortical microstimulation, immediately after rhizotomy and following a 2-week recovery period. Immediately after deafferentation we found that the size of the distal representation was reduced. However, despite this loss of input there were no changes in motor threshold. Two weeks after deafferentation, animals showed a further distal representation reduction, an expansion of the elbow representation, and a small elevation in distal movement threshold. These changes were specific to the forelimb map in the hemisphere contralateral to deafferentation; there were no changes in the hindlimb or intact-side forelimb representations. Degradation of the contralateral distal forelimb representation probably contributes to the motor control deficits after deafferentation. We propose that somatic sensory inputs are essential for the maintenance of the forelimb motor map in motor cortex and should be considered when rehabilitating patients with peripheral or spinal cord injuries or after stroke. PMID:24329730

Jiang, Yuqiu; Williams, Preston TJA; Martin, John H.

2013-01-01

2

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

NASA Technical Reports Server (NTRS)

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.

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

1984-01-01

3

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

PubMed

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 is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. PMID:25192655

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

2014-12-01

4

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

PubMed

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

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

2013-09-01

5

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

PubMed

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

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

2015-02-01

6

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

PubMed

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

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

2014-09-01

7

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

NASA Astrophysics Data System (ADS)

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

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

2011-06-01

8

A Novel Method for Assessing Proximal and Distal Forelimb Function in the Rat: the Irvine, Beatties and Bresnahan (IBB) Forelimb Scale  

PubMed Central

Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences of damage to this level of the spinal cord (Pearse et al., 2005, Gensel et al., 2006, Anderson et al., 2009), as the majority of human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss of forelimb function due to damage to the white matter affecting both descending motor and ascending sensory systems, and to the gray matter containing the segmental circuitry for processing sensory input and motor output for the forelimb. Additionally, a key priority for human patients with cervical SCI is restoration of hand/arm function (Anderson, 2004). Thus, outcome measures that assess both proximal and distal forelimb function are needed. Although there are several behavioral assays that are sensitive to different aspects of forelimb recovery in experimental models of cervical SCI (Girgis et al., 2007, Gensel et al., 2006, Ballerman et al., 2001, Metz and Whishaw, 2000, Bertelli and Mira, 1993, Montoya et al., 1991, Whishaw and Pellis, 1990), few techniques provide detailed information on the recovery of fine motor control and digit movement. The current measurement technique, the Irvine, Beatties and Bresnahan forelimb scale (IBB), can detect recovery of both proximal and distal forelimb function including digit movements during a naturally occurring behavior that does not require extensive training or deprivation to enhance motivation. The IBB was generated by observing recovery after a unilateral C6 SCI, and involves video recording of animals eating two differently shaped cereals (spherical and doughnut) of a consistent size. These videos were then used to assess features of forelimb use, such as joint position, object support, digit movement and grasping technique. The IBB, like other forelimb behavioral tasks, shows a consistent pattern of recovery that is sensitive to injury severity. Furthermore, the IBB scale could be used to assess recovery following other types of injury that impact normal forelimb function. PMID:21206464

Irvine, Karen-Amanda; Ferguson, Adam R.; Mitchell, Kathleen D.; Beattie, Stephanie B.; Beattie, Michael S.; Bresnahan, Jacqueline C.

2010-01-01

9

Encoding of forelimb forces by corticospinal tract activity in the rat  

PubMed Central

In search of a solution to the long standing problems encountered in traditional brain computer interfaces (BCI), the lateral descending tracts of the spinal cord present an alternative site for taping into the volitional motor signals. Due to the convergence of the cortical outputs into a final common pathway in the descending tracts of the spinal cord, neural interfaces with the spinal cord can potentially acquire signals richer with volitional information in a smaller anatomical region. The main objective of this study was to evaluate the feasibility of extracting motor control signals from the corticospinal tract (CST) of the rat spinal cord. Flexible substrate, multi-electrode arrays (MEA) were implanted in the CST of rats trained for a lever pressing task. This novel use of flexible substrate MEAs allowed recording of CST activity in behaving animals for up to three weeks with the current implantation technique. Time-frequency and principal component analyses (PCA) were applied to the neural signals to reconstruct isometric forelimb forces. Computed regression coefficients were then used to predict isometric forces in additional trials. The correlation between measured and predicted forces in the vertical direction averaged across six animals was 0.67 and R2 value was 0.44. Force regression in the horizontal directions was less successful, possibly due to the small amplitude of forces. Neural signals above and near the high gamma band made the largest contributions to prediction of forces. The results of this study support the feasibility of a spinal cord computer interface (SCCI) for generation of command signals in paralyzed individuals. PMID:24847198

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

2014-01-01

10

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

PubMed Central

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

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

2013-01-01

11

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

PubMed

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

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

2015-01-01

12

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

PubMed Central

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

2012-01-01

13

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

PubMed Central

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

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

14

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

PubMed

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

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

2012-02-10

15

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury  

NASA Astrophysics Data System (ADS)

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.

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

2013-08-01

16

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

PubMed Central

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

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

2014-01-01

17

A new rodent behavioral paradigm for studying forelimb movement  

PubMed Central

The center-out task is a standard paradigm often used to study the neural control of reaching movements in human and non-human primates. However, there are several disadvantages to the use of monkeys, notably costs, infrastructural requirements, and ethical considerations. Here we describe a similar task designed to examine forelimb movements in rats. Rats were trained to grasp a joystick with their forepaw and use it to control the movements of a sipper tube in two dimensions. The rats learned to move the joystick in four directions with at least 70% accuracy after about 45 days of training. In addition, rats were able to learn a reversed mapping between joystick and sipper tube movement. This is a more complicated behavior than has been previously demonstrated for rats, and it could allow more motor behavior studies to be conducted in rodents instead of monkeys. We currently are using this behavior to decode the ratsforelimb movements from their brain signals. PMID:20691727

Slutzky, Marc W.; Jordan, Luke R.; Bauman, Matthew J.; Miller, Lee E.

2010-01-01

18

Oxymatrine reduces neuroinflammation in rat brain  

PubMed Central

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

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

2012-01-01

19

Activity-Based Therapies To Promote Forelimb Use after a Cervical Spinal Cord Injury  

PubMed Central

Abstract Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways. PMID:19317604

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.

2009-01-01

20

Forelimb biomechanics of nonavian theropod dinosaurs in predation  

Microsoft Academic Search

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

Kenneth Carpenter

2002-01-01

21

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

PubMed

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

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

2008-02-01

22

Neuromuscular anatomy and evolution of the cetacean forelimb.  

PubMed

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

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

2007-09-01

23

Fructus aurantii reduced portal pressure in portal hypertensive rats.  

PubMed

The purpose of this study was to investigate the effects of Fructus Aurantii (the unripe fruits of Citrus aurantium L.) on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL) in Sprague-Dawley rats. Sham-operated (Sham) rats served as controls. Hemodynamic and in vitro contractile studies were performed at 14 days after surgery. Both the aqueous extract of Fructus Aurantii and synephrine, one of its purified principles with pressor activity, were infused into the conscious PVL and Sham rats via a syringe pump. Fructus Aurantii (1.25, 2.5, & 5.0 mg/kg/min) dose-dependently reduced portal pressure in PVL and Sham rats, with the percentage change in portal pressure more pronounced in PVL rats. Mean arterial pressure was dose-dependently elevated by Fructus Aurantii. Synephrine (0.095, 0.19, & 0.38 mg/kg/min) also dose-dependently reduced portal pressure and elevated mean arterial pressure in PVL and Sham rats. Fructus Aurantii (2.8-280 micrograms/ml) induced dose-dependent contractile responses mainly in aorta and mesenteric artery, but little response in portal vein. The results showed that Fructus Aurantii infusion reduced portal pressure, possibly by way of arterial vasoconstriction. PMID:7475952

Huang, Y T; Wang, G F; Chen, C F; Chen, C C; Hong, C Y; Yang, M C

1995-01-01

24

Architectural Properties of Distal Forelimb Muscles in Horses, Equus caballus  

E-print Network

were measured for nine distal forelimb muscles. Physiological cross-sectional area (PCSAArchitectural Properties of Distal Forelimb Muscles in Horses, Equus caballus Nicholas A.T. Brown,1. To accurately and noninvasively predict muscle and joint contact forces, a detailed model of musculoskeletal

Meyers, Ron

25

Functional implications of felid forelimb anatomy.  

PubMed

The elbow and wrist anatomy of 17 felid species were studied and compared with that of other representative mammaliam carnivores. Based on the shape and position of the olecranon fossa, it was determined that for felids the forelimb cannot travel in a "pendulum-like" motion during locomotion, but must travel through an arch away from the parasagittal plane of the body. For the anterior limb, the degree of deviation from the parasagittal plane was correlated with habitat preference. In this regard, those felids that are exclusive forest dwellers (found exclusively in high, densely structured habitats) had the greatest angle of inclination of the olecranon fossa. In addition, these, species had a large lateral olecranon tuberosity for the attachment of the lateral head of the triceps muscle. For those felids that inhabit more open terrain (low-structured habitat), the olecranon fossa was less inclined, the medical olecranon tuberosity relatively large, and the medial head of the triceps was significantly heavier than those of the forest felids. Both the wrist and elbow joints exhibited a large degree of mobility which was reflective of the claw-equipped forelimb being used as a hunting weapon. PMID:685643

Gonyea, W J

1978-01-01

26

Reduced neurons in the ileum of proctocolectomized rat models.  

PubMed

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

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

2014-11-29

27

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

PubMed Central

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

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

2014-01-01

28

Red maca (Lepidium meyenii) reduced prostate size in rats  

PubMed Central

Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions Red Maca, a cruciferous plant from the highland of Peru, reduced ventral prostate size in normal and TE treated rats. PMID:15661081

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

2005-01-01

29

Reduced motoneuron excitability in a rat model of sepsis  

PubMed Central

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW. PMID:23303860

Nardelli, Paul; Khan, Jaffar; Powers, Randall; Cope, Tim C.

2013-01-01

30

Evolutionary Morphology of the Tenrecoidea (Mammalia) Forelimb Skeleton  

Microsoft Academic Search

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

Justine A. Salton; Eric J. Sargis

31

Acetyl l -carnitine reduces impulsive behaviour in adolescent rats  

Microsoft Academic Search

The attention deficit\\/hyperactivity disorder (ADHD) can affect human infants and adolescents. One important feature of this disorder is behavioural impulsivity. This study assessed the ability of chronic acetyl-l-carnitine (ALC, saline or 100 mg\\/kg SC, plus 50 mg\\/kg orally) to reduce impulsivity in a validated animal model for ADHD. Food-restricted rats were tested during adolescence (postnatal days, pnd, 30–45) in operant chambers with

Walter Adriani; Monica Rea; Marta Baviera; William Invernizzi; Mirjana Carli; Orlando Ghirardi; Antonio Caprioli; Giovanni Laviola

2004-01-01

32

New, puzzling insights from comparative myological studies on the old and unsolved forelimb/hindlimb enigma.  

PubMed

Most textbooks and research reports state that the structures of the tetrapod forelimbs and hindlimbs are serial homologues. From this view, the main challenge of evolutionary biologists is not to explain the similarity between tetrapod limbs, but instead to explain why and how they have diverged. However, these statements seem to be related to a confusion between the serial homology of the vertebrate pelvic and pectoral appendages as a whole, and the serial homology of the specific soft- and hard-tissue structures of the tetrapod forelimbs and hindlimbs, leading to an even more crucial and puzzling question being overlooked: why are the skeletal and particularly the muscle structures of the forelimb and hindlimb actually so strikingly similar to each other? Herein we provide an updated discussion of these questions and test two main hypotheses: (i) that the similarity of the limb muscles is due to serial homology; and (ii) that tetrapods that use hindlimbs for a largely exclusive function (e.g. bipedalism in humans) exhibit fewer cases of similarity between forelimbs and hindlimbs than do quadrupedal species. Our review shows that of the 23 arm, forearm and hand muscles/muscle groups of salamanders, 18 (78%) have clear 'topological equivalents' in the hindlimb; in lizards, 14/24 (58%); in rats, 14/35 (40%); and in modern humans, 19/37 (51%). These numbers seem to support the idea that there is a plesiomorphic similarity and subsequent evolutionary divergence, but this tendency actually only applies to the three former quadrupedal taxa. Moreover, if one takes into account the total number of 'correspondences', one comes to a surprising and puzzling conclusion: in modern humans the number of forelimb muscles/muscle groups with clear 'equivalents' in the hindlimb (19) is substantially higher than in quadrupedal mammals such as rats (14), lizards (14) and even salamanders (18). These data contradict the hypothesis that divergent functions lead to divergent morphological structures. Furthermore, as we show that at least five of the 19 modern human adult forelimb elements that have a clear hindlimb 'equivalent' derive from embryonic anlages that are very different from the ones giving rise to their adult hindlimb 'equivalents', they also contradict the hypothesis that the similarity in muscle structures between the forelimb and hindlimb of tetrapods such as modern humans are due to their origin as serial homologues. This similarity is instead the result of phylogenetically independent evolutionary changes leading to a parallelism/convergence due to: (i) developmental constraints, i.e. similar molecular mechanisms are involved (particularly in the formation of the neomorphic hand), but this does not necessarily mean that similar anlages are used to form the similar adult structures; (ii) functional constraints, related to similar adaptations; (iii) topological constraints, i.e. limited physical possibilities; and even (iv) phylogenetic constraints, which tend to prevent/decrease the occurrence of new homoplasic similarities, but also help to keep older, ancestral homoplasic resemblances. PMID:22958734

Diogo, Rui; Linde-Medina, Marta; Abdala, Virginia; Ashley-Ross, Miriam A

2013-02-01

33

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

PubMed

We characterized the architecture, fiber type, titin isoform distribution, and collagen content of 27 portions of 22 muscles in the murine forelimb. The mouse forelimb was different from the human arm in that it had the extensor digitorum lateralis muscle and no brachioradialis muscle. Architecturally, the mouse forelimb differed from humans with regard to load bearing, having a much larger contribution from extensors than flexors. In mice, the extensor : flexor PCSA ratio is 2.7, whereas in humans it is only 1.4. When the architectural difference index was calculated, similarities became especially apparent between flexors and extensors of the distal forelimb, as well as pronators. Discriminant analysis revealed that biochemical measures of collagen, titin, and myosin heavy chain were all strong between-species discriminators. In terms of composition, when compared with similar muscles in humans, mice had, on average, faster muscles with higher collagen content and larger titin isoforms. This report establishes the anatomical and biochemical properties of mouse forelimb muscles. Given the prevalence of this species in biological studies, these data will be invaluable for studying the biological basis of mouse muscle structure and function. PMID:22938020

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

2012-11-01

34

Perindopril May Improve the Hippocampal Reduced Glutathione Content in Rats  

PubMed Central

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

Mashhoody, Tahereh; Rastegar, Karim; Zal, Fatemeh

2014-01-01

35

Acute nicotine reduces brain arachidonic acid signaling in unanesthetized rats  

PubMed Central

Nicotine exerts its central effects by activating pre- and post-synaptic nicotinic acetylcholine receptors (nAChRs). Pre-synaptic nAChRs modulate the release of many neurotransmitters that bind to post-synaptic receptors. These may be coupled to the activation of cytosolic phospholipase A2 (cPLA2), which hydrolyzes arachidonic acid (AA) from membrane phospholipids. We hypothesized that nicotine would modify brain signaling involving AA by binding to nAChRs. Nicotine (0.1 mg/kg s.c.) or saline was injected 2 or 10 min before infusing [1-14C]AA in unanesthetized rats. The AA incorporation coefficient k* (a marker of the AA signal) was measured in 80 brain regions by quantitative autoradiography. Nicotine, compared to saline, when given 2 min before [1-14C]AA, significantly decreased k* for AA in 26 regions, including cerebral cortex, thalamus and habenula-interpeduncular regions, by 13% to 45%. These decreases could be entirely prevented by pretreatment with mecamylamine (1.0 mg/kg s.c.). When given 10 min before [1-14C]AA, nicotine did not alter any value of k*. In summary, nicotine given to unanesthetized rats rapidly reduces signaling involving AA in brain regions containing nAChRs, likely by modulating pre-synaptic release of neurotransmitters. The effect shows rapid desensitization and is produced at a nicotine dose equivalent to smoking one cigarette in humans. PMID:19142197

Chang, Lisa; Rapoport, Stanley I.; Nguyen, Henry N.; Greenstein, Dede; Chen, Mei; Basselin, Mireille

2009-01-01

36

Dimensions of forelimb muscles in orangutans and chimpanzees.  

PubMed

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

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

2009-10-01

37

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

E-print Network

conditioning, rats were injected with saline, propranolol, or peripheral -receptor blocker sotalol (both 10 mg, sotalol did not affect fear expression, although both drugs significantly reduced heart rate

Quirk, Gregory J.

38

Forelimb-hindlimb developmental timing changes across tetrapod phylogeny  

PubMed Central

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

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

2007-01-01

39

Does endogenous progesterone promote recovery of chronic sensorimotor deficits following contusion to the forelimb representation of the sensorimotor cortex?  

PubMed

We studied sensorimotor recovery in male, normal-cycling and pseudopregnant female rats following unilateral FL-SMC contusions. Forelimb use (push off before a rear, support against the walls, and landing after a rear) and the foot fault test (foot misplacements during locomotion on an elevated grid) were analyzed from videotapes taken before surgery, and then again on post-surgical days 2 and 36. High endogenous progesterone levels in females at the time of injury did not affect recovery as there were no differences between males, pseudopregnant females and normal-cycling female rats on these behaviors. None of the brain-injured rats recovered symmetrical forelimb use between 2 and 36 days after injury (P>0.05) and they also showed foot misplacements (P>0.05) in the foot fault test. Male and female rats with contusions had fewer mean foot misplacements on day 36 than 2 days after injury (P<0.001), indicating that there was partial recovery on this task. These results were taken to show that there were no sex differences in motor deficits caused by unilateral FL-SMC injury. In addition, higher endogenous progesterone levels in females did not protect them from the chronic sensorimotor deficits caused by unilateral FL-SMC contusions. PMID:11080545

Grossman, K J; Stein, D G

2000-12-01

40

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.  

PubMed

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli. PMID:8666332

Llovet, J M; Bartolí, R; Planas, R; Viñado, B; Pérez, J; Cabré, E; Arnal, J; Ojanguren, I; Ausina, V; Gassull, M A

1996-04-01

41

PARP inhibition reduces acute colonic inflammation in rats.  

PubMed

Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20-40 mg/kg) and 1,5-dihydroxyisoquinoline (4-8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E2 (PGE2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS induction was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cells infiltration in the mucosa and necrosis. Furthermore, increased MPO activity, cyclooxygenase-2 expression and PGE2 synthesis were significantly augmented after TNBS instillation. On the contrary, treatment with 1,5-dihydroxyisoquinoline significantly reduced the degree of colon injury and also caused a substantial reduction in the rise in MPO activity, in the increase of staining for cyclooxygenase-2, as well as in the up-regulation of PGE2 caused by TNBS in the colon. Although nicotinamide significantly did not reduce macroscopic damage, it decreased both MPO activity and PGE2 colonic levels. In conclusion, we demonstrated that PARP inhibition can exert beneficial effects in experimental colitis and may, therefore, be useful in the treatment of ulcerative colitis. PMID:17374531

Sánchez-Fidalgo, Susana; Villegas, Isabel; Martín, Antonio; Sánchez-Hidalgo, Marina; Alarcón de la Lastra, Catalina

2007-06-01

42

Carvedilol protected diabetic rat hearts via reducing oxidative stress  

PubMed Central

Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats. PMID:16909474

Huang, He; Shan, Jiang; Pan, Xiao-hong; Wang, Hui-ping; Qian, Ling-bo

2006-01-01

43

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

PubMed Central

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

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

2014-01-01

44

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

PubMed

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

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

2014-05-01

45

Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis  

Microsoft Academic Search

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering\\u000a effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine\\u000a whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver\\u000a injury. Female rats were subjected to a sham (n = 10)

Sava? Demirbilek; Erkan Tas; Kubilay Gurunluoglu; Melih Akin; Rauf T. Aksoy; Memet H. Emre; Nasuhi E. Aydin; Selma Ay; Nilufer Ozatay

2007-01-01

46

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

Microsoft Academic Search

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

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

2000-01-01

47

Estrogen reduces CCL4- induced liver fibrosis in rats  

Microsoft Academic Search

AIM: Chronic liver diseases, such as fibrosis or cirrhosis, are more common in men than in women. This gender difference may be related to the effects of sex hormones on the liver. The aim of the present work was to investigate the effects of estrogen on CCL4-induced fibrosis of the liver in rats. METHODS: Liver fibrosis was induced in male,

Jun-Wang Xu; Jun Gong; Xin-Ming Chang; Jin-Yan Luo; Lei Dong; Zhi-Ming Hao; Ai Jia; Gui-Ping Xu

2002-01-01

48

Fore-Aft Ground Force Adaptations to Induced Forelimb Lameness in Walking and Trotting Dogs  

PubMed Central

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

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

2012-01-01

49

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

PubMed Central

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

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

2014-01-01

50

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

ERIC Educational Resources Information Center

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…

Lee, Scott A.; Thomas, Joshua D.

2014-01-01

51

Effect of walking velocity on forelimb kinematics and kinetics.  

PubMed

A database of biomechanical variables obtained from normal horses walking at a range of velocities is needed for comparison with the variables obtained from lame horses in which velocity cannot be predetermined. The objective was to investigate velocity-dependent changes in selected kinematic variables, ground reaction forces (GRF) and net joint energies in the forelimb and to develop statistical equations to calculate expected values of these variables for horses walking at different velocities. Five sound horses walked at a range of velocities (0.82 to 1.91 m/s) over a force plate. Kinematic data were recorded simultaneously for 51 trials. Kinematic, GRF and energetic variables were determined using standard methods. Correlation and simple regression analyses between velocity and measured variables were performed. An increase in walking velocity was correlated with an increase in stride length and decreases in stride and stance duration. Vertical, braking and propulsive impulses decreased as a consequence of the large reduction in stance duration, even though peak vertical, braking and propulsive GRFs increased. There was no significant increase in energy generation at any of the forelimb joints, indicating that muscle activity was not the source of the increase in GRFs. Changes in the longitudinal GRFs appeared to be influenced by velocity-dependent increases in head and neck oscillations. The equations obtained in this study can be used to calculate the expected normal variables from a range of walking velocities and to detect deviations from normal values in lame horses. PMID:12405709

Khumsap, S; Clayton, H M; Lanovaz, J L; Bouchey, M

2002-09-01

52

Functional anatomy of the cheetah (Acinonyx jubatus) forelimb  

PubMed Central

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

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

2011-01-01

53

Intraperitoneal capsaicin treatment reduces postoperative gastric ileus in awake rats  

Microsoft Academic Search

Introduction: Postoperative gastric ileus interferes with postoperative recovery of the patients. Previous studies suggest that capsaicin-sensitive afferent neurons are involved in the mediation of postoperative gastric ileus. Methods: A group of rats were equipped with a strain gauge transducer sutured to the gastric wall. Gastric motility was recorded after intraperitoneal injection of capsaicin (0.1 µmol\\/kg and 1 µmol\\/kg) or vehicle.

T. T. Zittel; T. Meile; E. C. Jehle; H. D. Becker

2001-01-01

54

Melatonin and taurine reduce early glomerulopathy in diabetic rats  

Microsoft Academic Search

Oxidative stress occurs in diabetic patients and experimental models of diabetes. We examined whether two antioxidants, melatonin and taurine, can ameliorate diabetic nephropathy. Enhanced expression of glomerular TGF-?1 and fibronectin mRNAs and proteinuria were employed as indices of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50 mg\\/kg. Two days after streptozotocin, diabetic rats were assigned to

Hunjoo Ha; Mi-Ra Yu; Kyung Hwan Kim

1999-01-01

55

Arginine administration reduces creatine kinase activity in rat cerebellum.  

PubMed

In the present study were evaluated the in vivo effects of arginine administration on creatine kinase (CK) activity in cerebellum of rats. We also tested the influence of antioxidants, namely alpha-tocopherol and ascorbic acid and the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the effects elicited by Arg in order to investigate the possible participation of nitric oxide (NO) and/or its derivatives peroxynitrite (ONOO(-)) and other/or free radicals on the effects of arginine on CK activity. Sixty-day-old rats were treated with a single i.p. injection of saline (control, group I), arginine (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20.0 mg/kg) (group III) or Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or 20.0 mg/kg) (group IV) and were killed 1 h later. In another set of experiments, the animals were pretreated for 1 week with daily i.p. administration of saline (control) or alpha-tocopherol (40 mg/kg) and ascorbic acid (100 mg/kg). Twelve hours after the last injection of the antioxidants, the rats received one i.p. injection of arginine (0.8 g/kg) or saline and were killed 1 h later. Results showed that total and cytosolic CK activities were significantly inhibited by arginine administration in cerebellum of rats, in contrast to mitochondrial CK activity which was not affected by this amino acid. Furthermore, simultaneous injection of L-NAME (20.0 mg/kg) and treatment with alpha-tocopherol and ascorbic acid prevented these effects. The data indicate that the reduction of CK activity in cerebellum of rats caused by arginine was probably mediated by NO and/or its derivatives ONOO(-)and other free radicals. Considering the importance of CK for the maintenance of energy homeostasis in the brain, if this enzyme inhibition also occurs in hyperargininemic patients, it is possible that CK inhibition may be one of the mechanisms by which arginine is neurotoxic in hyperargininemia. PMID:17235684

Delwing, Débora; Cornélio, Andrea R; Wajner, Moacir; Wannmacher, Clóvis M D; Wyse, Angela T S

2007-03-01

56

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

PubMed Central

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

Jiang, Enshe; Yu, Dongming; Feng, Zhifen

2013-01-01

57

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

PubMed

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 20days. 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

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

2015-01-01

58

Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats  

Microsoft Academic Search

Background. Neutrophil activation with concomitant matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) release has been implicated in the development of sepsis-induced acute lung injury. We hypothesized that COL-3, a chemically modified tetracycline known to inhibit MMP-2 and MMP-9, would reduce lung injury and improve survival in rats following cecal ligation and puncture (CLP).Methods. Sprague-Dawley rats were separated into five groups:

Jay Steinberg; Jeffrey Halter; Henry J Schiller; Monica Dasilva; Steve Landas; Louis A Gatto; Paivi Maisi; Timo Sorsa; Minna Rajamaki; Hsi-Ming Lee; Gary F Nieman

2003-01-01

59

Ibandronate affects bone growth and mineralization in rats with normal and reduced renal function  

Microsoft Academic Search

Bisphosphonates have been shown to attenuate ectopic calcification in experimental uremia. While they are known to reduce\\u000a bone turnover, the effects on endochondral bone formation have not yet been addressed. To address this issue, we administered\\u000a male Sprague-Dawley rats weekly subcutaneous injections of either vehicle or ibandronate (1.25 ?g\\/kg body weight) for a total\\u000a of 10 weeks. The rats were randomly allocated

Dagmar-Christiane Fischer; Claudia Jensen; Anja Rahn; Birgit Salewski; Günther Kundt; Geert J. Behets; Patrick D’Haese; Dieter Haffner

2011-01-01

60

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

PubMed

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

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

2010-08-01

61

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

PubMed Central

Pomegranate seed oil (PSO), which is the major source of conjugated linolenic acids such as punicic acid (PuA), exhibits strong anti-inflammatory properties. Necrotizing enterocolitis (NEC) is a devastating disease associated with severe and excessive intestinal inflammation. The aim of this study was to evaluate the effects of orally administered PSO on the development of NEC, intestinal epithelial proliferation, and cytokine regulation in a rat model of NEC. Premature rats were divided into three groups: dam fed (DF), formula-fed rats (FF), or rats fed with formula supplemented with 1.5% of PSO (FF + PSO). All groups were exposed to asphyxia/cold stress to induce NEC. Intestinal injury, epithelial cell proliferation, cytokine production, and trefoil factor 3 (Tff3) production were evaluated in the terminal ileum. Oral administration of PSO (FF+PSO) decreased the incidence of NEC from 61 to 26%. Feeding formula with PSO improved enterocyte proliferation in the site of injury. Increased levels of proinflammatory IL-6, IL-8, IL-12, IL-23, and TNF-? in the ileum of FF rats were normalized in PSO-treated animals. Tff3 production in the FF rats was reduced compared with DF but not further affected by the PSO. In conclusion, administration of PSO protects against NEC in the neonatal rat model. This protective effect is associated with an improvement of intestinal epithelial homeostasis and a strong anti-inflammatory effect of PSO on the developing intestinal mucosa. PMID:22821948

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

2012-01-01

62

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

PubMed

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

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

2013-03-01

63

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

PubMed Central

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

Milliken, Garrett W.; Plautz, Erik J.

2013-01-01

64

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

PubMed Central

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

65

Behavioral deficits, abnormal corticosterone, and reduced prefrontal metabolites of adolescent rats subject to early life stress  

PubMed Central

The present study investigated the effect of early life stress in adolescent rats on brain metabolites, serum corticosterone, and depressive-like behavior. A group of rats were subject to early life stress from postnatal day (PND) 1 to 14. A matched control group was studied. Behavioral tests, serum corticosterone and high-resolution proton magnetic resonance spectroscopy were conducted between PND 30 and 40. In this study, adolescent rats exposed to early life stress demonstrated depressive-like behavior and increased serum corticosterone during adolescence. They also showed reduced glutamate, glutamine, and N-acetyl aspartate (NAA) levels in the prefrontal cortex. A reduced myo-inositol level, consistent with astroglial deficits, was observed but was not statistically significant. Together, these findings characterize the effect of early life stress on adolescent animals and underscore the long-lasting and detrimental effects of childhood adversities. PMID:23643993

Zhang, Jie; Abdallah, Chadi G.; Chen, Yaowen; Huang, Tianhua; Huang, Qingjun; Xu, Chongtao; Xiao, Yeyu; Liu, Yuzhen; Ding, Yan; Wu, Renhua

2013-01-01

66

ELECTRICAL STIMULATION REDUCES AGE RELATED ATROPHY AND WEAKNESS IN EDL MUSCLES OF RATS  

E-print Network

ELECTRICAL STIMULATION REDUCES AGE RELATED ATROPHY AND WEAKNESS IN EDL MUSCLES OF RATS D.E. Dow, USA Abstract: Skeletal muscles atrophy and weaken with old age. The number of motor-units decreases with age [5]. Denervated fibres undergo no contractile activity, atrophy and contribute to whole muscle

Dennis, Robert G.

67

Enalapril reduces collagen type IV synthesis and expansion of the interstitium in the obstructed rat kidney  

Microsoft Academic Search

Enalapril reduces collagen type IV synthesis and expansion of the interstitium in the obstructed rat kidney. Chronic unilateral ureteral obstruction (UUO) results in interstitial fibrosis of the affected kidney. In this study we determined that enalapril ameliorates the increased production of extracellular matrix (ECM) protein in the tubulointerstitium during UUO. The relative volume (Vv) of the tubulointerstitium measured by a

Hiroyuki Kaneto; Jeremiah Morrissey; Ruth McCracken; Alvaro Reyes; Saulo Klahr

1994-01-01

68

Decreased brain zinc availability reduces hippocampal neurogenesis in mice and rats  

Microsoft Academic Search

In the adult brain, neurogenesis occurs in the subgranular zone of the dentate gyrus (DG), where high levels of vesicular zinc are localized in the presynaptic terminals. To determine whether zinc has a role in modulating hippocampal neurogenesis under normal or pathologic conditions, we manipulated the level of vesicular zinc experimentally. To reduce hippocampal vesicular zinc, rats were either fed

Sang Won Suh; Seok Joon Won; Aaron M Hamby; Byung Hoon Yoo; Yang Fan; Christian T Sheline; Haruna Tamano; Atsushi Takeda; Jialing Liu

2009-01-01

69

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

Microsoft Academic Search

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

Laurie E. Iten; Susan V. Bryant

1973-01-01

70

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

PubMed

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

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

2014-03-01

71

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

PubMed Central

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

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

2014-01-01

72

2-Arachidonoylglycerol into the lateral hypothalamus improves reduced sleep in adult rats subjected to maternal separation.  

PubMed

We have previously reported that maternal separation (MS) for 3 h daily during the first two postnatal weeks increases wakefulness, whereas it reduces sleep in rats. Oleamide, an agonist of the cannabinoid receptor type 1, increases sleep in MS rats to such a level that we cannot differentiate their sleep patterns from those of their non-MS (NMS) siblings. However, 2-arachidonoylglycerol (2-AG), an endocannabinoid, infused into the lateral hypothalamus of NMS rats at the beginning of the dark phase of the cycle increases rapid eye movement sleep and the expression of c-Fos on the rapid eye movement sleep promoting melanin-concentrating hormone neurons. We recorded the sleep-wake cycle of adult rats subjected to MS for 3 h daily from postnatal days 2 to 16, as well as in their NMS siblings. Besides the electrodes for recording the sleep-wake cycle, a couple of cannulae aimed bilaterally to the lateral hypothalamus were implanted to infuse 2-AG. We found that administration of 2-AG into the lateral hypothalamus of MS rats at the beginning of the light phase of the cycle restores sleep, whereas sleep and wakefulness of NMS rats under 2-AG infusion do not show any significant change. PMID:25356522

Pérez-Morales, Marcel; Fajardo-Valdez, Alfonso; Méndez-Díaz, Mónica; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

2014-12-17

73

Reduced arginine plasma levels are the drive for arginine production by the kidney in the rat.  

PubMed

In bile duct ligated rats, arginase (ASE) release from damaged hepatocytes results in low arginine (ARG) levels despite maximal renal ARG production. Plasma ARG levels were restored by reducing gut-derived endotoxemia that lowered circulating ASE activity although maintaining increased renal production. From this it was not clear if the higher renal ARG production was induced by the low grade endotoxemia or the low arginine plasma levels. The separate and combined influence of both factors on ARG metabolism was studied in the rat. Male Wistar rats received either bovine liver ASE, to lower ARG levels, or saline (SAL). Following the ASE or SAL infusion, rats were randomized to receive a low dose endotoxin (LPS) or SAL infusion. In ASE/SAL- and ASE/LPS-treated rats, ARG levels were lower compared with SAL/SAL (p<.005) and SAL/LPS (p<.005). The increased ARG production by the kidneys and gut proved to be independent of LPS but related to reduced ARG plasma levels (both p<.05 when compared with SAL/SAL and SAL/LPS). Metabolism of related amino acids was not explanatory. The study concluded that a low grade endotoxemia did not influence the metabolism of ARG by the gut, kidney, and liver. Reductions in ARG plasma by ASE treatment, irrespective a low dose endotoxin, were the drive for ARG production by the gut and the kidney. PMID:10188773

Prins, H A; Houdijk, A P; Wiezer, M J; Teerlink, T; van Lambalgen, A A; Thijs, L G; van Leeuwen, P A

1999-03-01

74

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

PubMed

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

Shi, Song-sheng; Yang, Wei-zhong; Chen, Ye; Chen, Jian-ping; Tu, Xian-kun

2014-05-01

75

Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats.  

PubMed

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction. PMID:20204486

Tu, Xian-kun; Yang, Wei-zhong; Wang, Chun-hua; Shi, Song-sheng; Zhang, Yong-liang; Chen, Chun-mei; Yang, Yi-kun; Jin, Chang-dan; Wen, Shuai

2010-10-01

76

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

PubMed Central

Study design Experimental, controlled, animal study. Objectives To use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion. Setting Baltimore. Methods Adult female Long–Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide). Results MRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (P<0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P>0.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (P<0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated with significantly better neurological function (unilateral BBB scores) at 24 h in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral (median scores, 12 vs 2; P<0.001) hindlimbs. Conclusion MRI is an accurate non-invasive imaging biomarker of lesion expansion and is a sensitive measure of the ability of glibenclamide to reduce lesion expansion. PMID:24042989

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

2014-01-01

77

Serotonin transporter knockout rats show improved strategy set-shifting and reduced latent inhibition.  

PubMed

Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT(-/-)) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting (EDSS), heavily depends on the medial prefrontal cortex. This region shows functional changes in 5-HTT(-/-) rodents as well. Here we subjected 5-HTT(-/-) rats and their wild-type counterparts to an EDSS paradigm and a supplementary latent inhibition task. Results indicate that 5-HTT(-/-) rats also show improved EDSS, and indicate that reduced latent inhibition may contribute as an underlying mechanism. PMID:22505721

Nonkes, Lourens J P; van de Vondervoort, Ilse I G M; de Leeuw, Mark J C; Wijlaars, Linda P; Maes, Joseph H R; Homberg, Judith R

2012-05-01

78

Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat.  

PubMed

Administration of human FSH (hFSH) to cyclic rats during the dioestrous phase attenuates progesterone receptor (PR)-dependent events of the preovulatory LH surge in pro-oestrus. The increased bioactivity of the putative ovarian gonadotropin surge inhibiting/attenuating factor induced by hFSH treatment is not associated with a decrease in PR protein expression, and the possibility of its association at a PR posttranslational effect has been raised. The present experiments aimed to analyse PR phosphorylation status in the gonadotrope of rats with impaired LH secretion induced by in vivo hFSH injection. Two experimental approaches were used. First, incubated pro-oestrous pituitaries from hFSH-injected cycling and oestrogen-treated ovariectomized (OVX) rats were used to analyze the effect of calyculin, an inhibitor of intracellular phosphatases, on PR-dependent LH release, which was measured in the incubation medium by RIA. Second, pituitaries taken from hFSH-injected intact cycling and OVX rats and later incubated with P or GNRH1 were used to assess the phosphorylation rate of gonadotrope. The latter was analysed in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry using a MAB that recognizes the phosphorylated (p) form of PR at Ser294. Calyculin reduced the ovary-mediated inhibition of hFSH in GNRH1-stimulated LH secretion. In addition, the immunohistochemical expression of pSer294 PR was significantly reduced after ovarian stimulation with hFSH in pituitaries from pro-oestrous rats incubated with P or GNRH1. Altogether, these results suggested that the ovarian-dependent inhibitory effect of FSH injection on the preovulatory LH secretion in the rat may involve an increase in dephosphorylation of PR. PMID:18936085

Gordon, Ana; Garrido-Gracia, José C; Aguilar, Rafaela; Guil-Luna, Silvia; Millán, Yolanda; de Las Mulas, Juana Martín; Sánchez-Criado, José E

2009-01-01

79

Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure.  

PubMed

Previous animal and human studies have suggested that a muscle reflex engaged during contraction leads to heightened levels of sympathetic activity in congestive heart failure (CHF). The present experiment was designed to test the role for bradykinin, which is produced within contracting skeletal muscle and contributes to the muscle reflex through its action on kinin B(2) receptors located on the endings of thin fiber muscle afferents. CHF was induced in rats by myocardial infarction (MI) after coronary artery ligation. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. In the decerebrate rats, we examined renal sympathetic nerve activity (RSNA) during 1 min intermittent (1 to 4 s stimulation to relaxation) contraction of left triceps surae muscles. RSNA responded synchronously as tension was developed, and the response was significantly (P < 0.05) greater in MI rats [+39 +/- 9% s(-1) (integrated RSNA over time); n = 16] with 20 +/- 2% of FS than that in control healthy rats (+19 +/- 2% s(-1); n = 16) with 49 +/- 2% of FS. Tension development did not differ significantly between the two groups of rats. Thirty minutes after intra-arterial injection into the hindlimb circulation of the kinin B(2) receptor antagonist, HOE-140 (2 microg/kg), the RSNA response to contraction was significantly reduced in the MI rats (+26 +/- 7% s(-1)) but not in the control rats (+17 +/- 2% s(-1)). These data suggest that bradykinin within contracting muscle is part of the exaggerated muscle reflex seen in CHF. PMID:20207818

Koba, Satoshi; Xing, Jihong; Sinoway, Lawrence I; Li, Jianhua

2010-05-01

80

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

PubMed Central

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

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

2010-01-01

81

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

PubMed

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis. © 2014 Wiley Periodicals, Inc. PMID:25042403

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

2015-01-01

82

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

PubMed Central

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

2014-01-01

83

Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress.  

PubMed

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. Reactive oxygen species are important mediators of GEN-induced nephrotoxicity. Because of the strong antioxidant properties of pomegranate extract (PE), we evaluated the protective effect of PE against GEN-induced nephrotoxicity. Thirty-two adult male rats were randomly divided into four equal groups: (1) controls; (2) treated with GEN for 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water; and (4) treated with GEN plus PE (100 ?L). After 15 days, the rats were killed and their kidneys were taken, and blood analysis was performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically; and biochemically, nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels in kidneys were determined. Urea, creatinine, Na(+), and K(+) levels were investigated in the blood analysis. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone than rats in the control and the GEN + PE-treated groups. The GSH level in renal tissue of only GEN-treated rats was significantly lower than those in the control group, and administration of PE to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and PE had significantly lower MDA levels in kidney cortex tissue than those given GEN alone. There was no significant difference of NO levels between the groups. In rats treated with GEN + PE, despite the presence of mild tubular degeneration and tubular necrosis is less severe, and glomeruli maintained a better morphology when compared with the GEN-treated group. We think that PE prevents kidney damage by decreasing oxidative stress in kidney. PMID:23176634

Cekmen, Mustafa; Otunctemur, Alper; Ozbek, Emin; Cakir, Suleyman Sami; Dursun, Murat; Polat, Emre Can; Somay, Adnan; Ozbay, Nurver

2013-01-01

84

Edaravone reduces mitochondrial damage due to reperfusion injury following leg ischemia in rats  

PubMed Central

PURPOSE: Free radicals have been implicated in reperfusion injury. It was shown that the free radical scavenger edaravone might suppress reperfusion injury in rat extremities. The present study aimed to elucidate how edaravone suppresses reperfusion injury, focusing on its effect on the mitochondrial structure and glycogen storage in the lower extremity muscles. METHODS: Sixteen male Lewis rats (mean [± SD] weight 497±32 g) were divided into two groups and injected with either 3.0 mg/kg of edaravone (edaravone group, n=8 rats) or the same dose of saline (control group, n=8 rats) into the peritoneal cavity. The rat reperfusion injury models were created by clamping the bilateral common femoral arteries for 5 h, then declamping. The muscles were harvested more than 5 h after the start of reperfusion. The mitochondrial damage, defined as mitochondrial swelling, was examined using a transmission electron microscope at ×30,000 original magnification (n=3 for each rat). Glycogen storage, defined as a positive periodic acid-Schiff stain area, was examined using computerized densitometry (n=5 sections for each rat). RESULTS: The mitochondria in the control group demonstrated marked swelling (mean mitochondrial size = 0.169±0.059 ?m2). However, the mitochondria in the edaravone group had significantly less swelling (mean mitochondrial size = 0.102±0.036 ?m2; P<0.01). The mean percentage of positive periodic acid-Schiff stain was also significantly higher in the edaravone group than in the control group (51.7±6.8% versus 7.3±2.1%; P<0.01). CONCLUSION: The results suggested that edaravone reduces mitochondrial damage due to reperfusion injury, resulting in a high level of glycogen storage. PMID:22479143

Yamamura, Mitsuhiro; Miyamoto, Yuji; Mitsuno, Masataka; Tanaka, Hiroe; Ryomoto, Masaaki; Fukui, Shinya; Yoshioka, Yoshiteru

2010-01-01

85

Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat.  

PubMed

Evidence suggests that the hyperammonemia (HA)-induced neuroinflammation and alterations in the serotonin (5-HT) system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy (HE). Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 (10(9) CFU mL(-1)) in drinking water as a daily supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxiety-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers: inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 ? in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats. PMID:24554471

Luo, Jia; Wang, Tao; Liang, Shan; Hu, Xu; Li, Wei; Jin, Feng

2014-03-01

86

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

PubMed

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

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

2013-05-01

87

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

PubMed Central

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

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

2013-01-01

88

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

PubMed Central

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

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

2013-01-01

89

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

PubMed

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

Stalheim-Smith, A

1984-04-01

90

Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in diabetic rats.  

PubMed

Glomerular thromboxane production and urinary thromboxane excretion are increased in early diabetes, but in spite of this renal blood flow and glomerular filtration rate are significantly higher than in control animals. To study the possibility of a defect in thromboxane actions in the kidney, we have measured glomerular thromboxane receptors and the renal hemodynamic response to the administration of a stable thromboxane analog in diabetic rats. Glomerular thromboxane receptors were studied in hyperglycemic diabetic rats 7 to 10 days after injection of streptozotocin (65 mg/kg, i.v.) and in normal controls. Scatchard analysis of equilibrium binding using the thromboxane antagonist, [3H]-SQ29548, demonstrated one class of high affinity thromboxane receptor sites in control (Kd = 19.9 +/- 2.6 nM, N = 16) and diabetic rats (Kd = 19.8 +/- 2.1 nM, N = 8, P = NS). The number of thromboxane receptors was reduced by 44% in diabetic rats (control, 374 +/- 20 vs. diabetic, 210 +/- 21 fmol/mg, P less than 0.01). Thromboxane binding in diabetic rats was not restored to normal levels by thromboxane synthetase inhibition with OKY046. Diabetic rats had higher renal blood flow (diabetic, 7.03 +/- 0.18 vs. control, 6.33 +/- 0.13 ml/min, P less than 0.05) and glomerular filtration rate (2.42 +/- 0.10 vs. 1.96 +/- 0.07 ml/min, P less than 0.05). Infusion of the stable thromboxane agonist, U46619 (0.1 micrograms/kg/min), reduced renal blood flow and glomerular filtration rate in all animals, but the constrictor responses were blunted by 50% in hyperglycemic diabetic rats compared with normal controls or euglycemic diabetic rats (P less than 0.05). Control of blood glucose with insulin normalized the number of glomerular thromboxane receptor sites, reversed hyperfiltration and restored glomerular responses to thromboxane agonist. The abnormalities of glomerular thromboxane receptors are similar to changes in angiotensin II receptors, and suggest a generalized defect in vasoconstrictor receptors in the diabetic kidney. PMID:1387436

Wilkes, B M; Kaplan, R; Mento, P F; Aynedjian, H S; Macica, C M; Schlondorff, D; Bank, N

1992-04-01

91

Genome-Wide Mapping of Chromatin State of Mouse Forelimbs  

PubMed Central

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

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

2014-01-01

92

Levodropropizine reduces capsaicin- and substance P-induced plasma extravasation in the rat trachea.  

PubMed

We investigated the effect of the non-opioid, peripherally acting antitussive agent levodropropizine to reduce neurogenic plasma extravasation in the rat trachea. Levodropropizine (10, 50 and 200 mg/kg) reduced in a dose-dependent manner the extravasation of Evans blue dye evoked by capsaicin. Levodropropizine inhibited also substance P-evoked extravasation, whereas it did not affect the extravasation evoked by platelet activating factor. Levodropropizine (10 and 100 microM) did not affect the contraction produced by [Sar9,Met(O2)11]substance P, a selective agonist for tachykinin NK1 receptors, in the rat urinary bladder in vitro. These data indicate that levodropropizine inhibits capsaicin-induced plasma extravasation: (a) acting at a postjunctional level; (b) exhibiting neuropeptide selectivity and; (c) via a mechanism independent of tachykinin NK1 receptor blockade. Irrespective of the mechanism, this novel antiinflammatory action of levodropropizine underlines its potential role in inflammatory airway diseases such as bronchial asthma. PMID:7504629

Yamawaki, I; Geppetti, P; Bertrand, C; Huber, O; Daffonchio, L; Omini, C; Nadel, J A

1993-10-12

93

Reduced Forebrain Serotonin Transmission is Causally Involved in the Development of Compulsive Cocaine Seeking in Rats  

PubMed Central

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

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

2012-01-01

94

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

PubMed Central

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

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

2015-01-01

95

Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release.  

PubMed

Urethan is a commonly used animal anesthetic for nonrecovery laboratory surgery. However, urethan has diverse biological effects that may complicate the interpretation of experimental findings. This study examined the effect of urethan on the response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg) in rats. In instrumented rats, urethan (1.2 gm/kg i.p.) completely prevented the fall in arterial pressure immediately after LPS administration but did not prevent late cardiovascular collapse. In uninstrumented rats, urethan also attenuated indexes of organ injury measured 4 h after LPS administration, including mural bowel hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and lung myeloperoxidase activity, a measure of neutrophil sequestration. The peak increase in tumor necrosis factor-alpha (TNF-alpha) 90 min after LPS administration was reduced 88% by urethan (2,060 +/- 316 vs. 16,934 +/- 847 pg/ml; P < 0.001). In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90% mortality rate of a lethal dose of LPS to 0-10% when given up to 24 h before LPS administration but did not reduce mortality when given 2 h after LPS. Urethan neither directly bound LPS by Limulus assay nor inhibited LPS-stimulated TNF-alpha mRNA expression in cultured mouse peritoneal macrophages, but TNF-alpha mRNA expression was suppressed by serum from a urethan-treated rat. Moreover, rauwolscine, which shares alpha 2-adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF-alpha release and speculate that this may be mediated by alpha 2-adrenoceptors. These actions of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS. PMID:8941558

Kotanidou, A; Choi, A M; Winchurch, R A; Otterbein, L; Fessler, H E

1996-11-01

96

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

PubMed

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

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

2015-01-14

97

Pyridoxine Administration Improves Behavioral and Anatomical Outcome after Unilateral Contusion Injury in the Rat  

PubMed Central

Abstract The purpose of this project was to evaluate the preclinical efficacy of pyridoxine, or vitamin B6. Rats received a 3.0?mm unilateral controlled cortical impact (CCI) injury of the sensorimotor cortex or sham surgery. Treatment with vitamin B6 (600 or 300?mg/kg IP) or vehicle was administered at 30?min and 24?h post-CCI. Somatosensory dysfunction was evaluated with the vibrissae–forelimb placing and bilateral tactile adhesive removal tests. Sensorimotor dysfunction was evaluated with the locomotor placing and the forelimb asymmetry tests. On the forelimb asymmetry test both treatment groups displayed no asymmetry bias on any of the testing days post-CCI and were statistically no different than the shams. Both vitamin B6 groups displayed a significant improvement in behavioral performance on the locomotor placing test compared to the vehicle-treated group. Administration of 600?mg/kg also significantly reduced tactile adhesive removal latencies on days 2, 4, 6, and 12 post-CCI. Both treatment groups were improved in their rate of recovery post-CCI on the vibrissae–forelimb placing test, but only the recovery seen in the 600-mg/kg group was significantly improved compared to vehicle. Finally, the 600-mg/kg dose resulted in significant cortical sparing compared to the vehicle-treated group. In general, the effects of vitamin B6 on recovery of function were dose-dependent, with the 600-mg/kg dose consistently showing greater recovery than the 300-mg/kg dose. More experimental analyses are warranted to evaluate the potential preclinical efficacy and mechanistic action of vitamin B6. PMID:20486803

Kuypers, Nicholas J.

2010-01-01

98

Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats.  

PubMed

Major depression is one of the most prevalent mental disorders in the population. In addition to genetic influences, disturbances in fetal nervous system development might be a contributing factor. Maternal infection during pregnancy may affect fetal brain development and consequently lead to neurological and mental disorders. Previously, we used low-dose lipopolysaccharide (LPS) exposure on embryonic day 10.5 to mimic mild maternal infection in rats and found that dopaminergic and serotonergic neurons were reduced in the offspring. The offspring also showed more anxiety-like behavior and an enhanced stress response. In the present study we used forced swim test and chronic mild stress challenge to assess depression-like behaviors in the affected offspring and examined their adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) concentration. Our results showed that prenatally LPS-exposed rats (LPS rats) displayed more depression-like behaviors and had reduced adult neurogenesis and BDNF. The behavioral abnormalities and reduction in adult neurogenesis could be reversed by chronic fluoxetine (FLX) treatment. This study demonstrates that during the critical time of embryonic development LPS exposure can produce long-term behavioral changes and reduction in adult neurogenesis. The findings of enhanced depression-like behaviors, reduced adult neurogenesis, and their responsiveness to chronic antidepressant treatment suggest that prenatal LPS exposure could serve as an animal model of depression. PMID:24177209

Lin, Yu-Lung; Wang, Sabrina

2014-02-01

99

Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart  

PubMed Central

Aging impairs function in the nonischemic heart and is associated with mechanical remodeling. This process includes accumulation of collagen (i.e., fibrosis) and dysregulation of active matrix metalloproteinases (MMPs). Exercise training (ET) improves cardiac function, but the pathways of protection remain poorly understood. Young (3 mo) and old (31 mo) FBNF1 rats were assigned into sedentary and exercise groups, with ET group rats training on a treadmill 45 min/d, 5 d/wk for 12 wk. Nonlinear optical microscopy (NLOM), histology, immunohistochemistry (IHC), and Western blot analyses were performed on the left ventricle and septum. NLOM, IHC, and histological imaging revealed that ET reduced age-associated elevation of collagen type I fibers. Active MMP-1, active MMP-2, and MMP-14 in the ECM fraction of the left ventricle were reduced by aging, an effect abrogated by ET. Tissue inhibitor of MMP (TIMP-1) was elevated with age but protected by ET. Transforming growth factor-? (TGF-?), upstream regulator of TIMP-1, increased with age but was attenuated by ET. Therefore, exercise training could protect the aging heart against dysregulation of MMPs and fibrosis by suppressing elevation of TIMP-1 and TGF-?.—Kwak, H.-B., Kim, J.-H., Joshi, K., Yeh, A., Martinez, D. A., Lawler, J. M. Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart. PMID:21148111

Kwak, Hyo-Bum; Kim, Jong-hee; Joshi, Kumar; Yeh, Alvin; Martinez, Daniel A.; Lawler, John M.

2011-01-01

100

Nuclear factor ?B inhibition reduces lung vascular lumen obliteration in severe pulmonary hypertension in rats.  

PubMed

NF-?B and IL-6, a NF-?B downstream mediator, play a central role in the inflammatory response of tissues. We aimed to determine the role of the classical NF-?B pathway in severe pulmonary arterial hypertension (PAH) induced by SU5416 and chronic hypoxia (SuHx) in rats. Tissue samples from patients with idiopathic PAH (iPAH) and control subjects were investigated. SuHx rats were treated from Days 1 to 3, 1 to 21, and 29 to 42 with the NF-?B inhibitor pyrrolidine dithiocarbamate (PDTC) and/or from Days 1 to 21 with anti-IL-6 antibody. Nuclear staining for NF-?B, an indicator of the activation of the classical NF-?B pathway, was detected in pulmonary arterial lesions of patients with iPAH and SuHx rats. NF-?B inhibition with PDTC prevented and reduced pulmonary arterial obliteration without reducing muscularization. However, the elevated lung levels of IL-6 were not reduced in PDTC-treated SuHx animals. PDTC treatment prevented or reduced apoptosis of pulmonary artery wall cells and pulmonary arterial obliteration. IL-6 inhibition had only a partial effect on apoptosis and obliteration. Pulmonary arterial media wall thickness was not affected by any of these treatments. Preventive and therapeutic PDTC treatment promoted immune regulation by increasing the number of perivascular CD4(+) T cells, in particular regulatory T cells (early treatment), and by reducing the number of perivascular CD8(+) T lymphocytes and CD45RA(+) B lymphocytes. Therapeutic PDTC treatment further preserved right ventricular function in SuHx animals. Inhibition of NF-?B may represent a therapeutic option for pulmonary arterial obliteration via reduced vessel wall cell apoptosis and improved regulation of the immune system. PMID:24684441

Farkas, Daniela; Alhussaini, Aysar A; Kraskauskas, Donatas; Kraskauskiene, Vita; Cool, Carlyne D; Nicolls, Mark R; Natarajan, Ramesh; Farkas, Laszlo

2014-09-01

101

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

PubMed

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

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

2012-09-10

102

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

Microsoft Academic Search

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

Louise H. Greenberg; Benjamin Weiss

1978-01-01

103

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

PubMed Central

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

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

2014-01-01

104

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

PubMed Central

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

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

2014-01-01

105

ACE inhibition reduces proteinuria, glomerular lesions and extracellular matrix production in a normotensive rat model of immune complex nephritis  

Microsoft Academic Search

ACE inhibition reduces proteinuria, glomerular lesions and extracellular matrix production in a normotensive rat model of immune complex nephritis. We studied the effect of the angiotensin converting enzyme (ACE) inhibitor, quinapril, on the clinical and morphological lesions of a normotensive model of immune complex nephritis. Untreated rats developed massive nephrotic syndrome, intense cell proliferation and glomerular and tubulointerstitial lesions. In

Marta Ruiz-Ortega; Silvia González; Daniel Serón; Enric Condom; Carmen Bustos; Raquel Largo; Eva González; Alberto Ortiz; Jesus Egido

1995-01-01

106

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

PubMed Central

The response to myocardial ischemia is complex and involves the cardio-cardiac sympathetic reflex. Specifically, cardiac spinal (sympathetic) afferents are excited by ischemic metabolites and elicit an excitatory sympathetic reflex, which plays a major role in the genesis of ventricular arrhythmias. For example, brief myocardial ischemia leads to ATP release, which activates cardiac spinal afferents through stimulation of P2 receptors. Clinical work with patients and preclinical work with animals document that disruption of this reflex protects against ischemia-induced ventricular arrhythmias. However, the role of afferent signals in the initiation of sustained ventricular tachycardia has not been investigated. Therefore, we tested the hypothesis that cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in adult (12–15 wk of age), conscious, male Sprague-Dawley rats. To test this hypothesis, the susceptibility to ventricular tachyarrhythmias produced by occlusion of the left main coronary artery was determined in two groups of conscious rats: 1) deafferentation (bilateral excision of the T1-T5 dorsal root ganglia) and 2) control (sham deafferentation). The ventricular arrhythmia threshold (VAT) was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Results document a significantly higher VAT in the deafferentation group (7.0 ± 0.7 min) relative to control (4.3 ± 0.3 min) rats. The decreased susceptibility to tachyarrhythmias with deafferentation was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST segment elevation) during ischemia. PMID:21677267

Lujan, Heidi L.; Krishnan, Sandhya

2011-01-01

107

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

PubMed Central

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

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

2012-01-01

108

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

Microsoft Academic Search

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

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

2009-01-01

109

Resolvin D1 reduces the immunoinflammatory response of the rat eye following uveitis.  

PubMed

This study investigated whether the administration of resolvin D1 to rats with endotoxininduced uveitis (EIU) ameliorates the immuno-inflammatory profile of the eye. 24?h after the administration of 200??g LPS into the footpad of Sprague-Dawley rats, severe changes of the structure of the eye occurred concomitantly with a severe inflammatory and immune response. These latter included strong infiltration of PMN leukocytes CD11b(+) T-lymphocytes CD4(+) and CD8(+) within the eye and a significant release of the cytokines/chemokines TNF-alpha, CXCL8, and RANTES too. Bolus of resolvin D1 (RvD1; 10-100-1000?ng/kg in 200??L of sterile saline via the tail vein) significantly and dose-dependently (i) reduced the development of the ocular derangement caused by LPS; (ii) reduced the clinical score attributed to EIU; (iii) reduced the protein concentration and myeloperoxidase activity (MPO) in aqueous humor (AqH); and (iv) reduced neutrophils, T-lymphocytes, and cytokines within the eye. PMID:23304060

Settimio, Rossi; Clara, Di Filippo; Franca, Ferraraccio; Francesca, Simonelli; Michele, D'Amico

2012-01-01

110

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

PubMed

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

Frisbee, J C

2001-10-01

111

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

PubMed Central

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

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

112

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

Microsoft Academic Search

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

Cinnamon M. Pace; Richard W. Blob; Mark W. Westneat

2001-01-01

113

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

PubMed Central

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

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

114

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

PubMed

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

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

2014-03-15

115

Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass.  

PubMed Central

The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/- 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure. PMID:1522231

Lafayette, R A; Mayer, G; Park, S K; Meyer, T W

1992-01-01

116

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

PubMed

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

Dienel, Gerald A; Cruz, Nancy F

2014-12-01

117

Conjugated linoleic acid does not reduce body fat but decreases hepatic steatosis in adult Wistar rats.  

PubMed

The dietary fatty acid conjugated linoleic acid (CLA) reduces hepatic lipid accumulation in some rodent models for obesity and hepatic steatosis. However, these effects are variable and complex due to differences in isomer responses and degree and sensitivity to changes in adiposity. Here, we hypothesized that CLA decreases hepatic steatosis in a diet-induced model of obesity in rats which are resistant to the adipose-lowering effects of CLA. To investigate this, we fed male Wistar rats a high-fat (20%) diet for 4 weeks to induce obesity and hepatic steatosis followed by low-fat (6.5%) experimental diets containing either 6.5% soybean oil (CON) or 1.5% CLA triglyceride mix plus 5% soybean oil (CLA). Dietary CLA significantly lowered hepatic triglycerides without changing weight, adiposity or adipokines, and was associated with significantly lower hepatic fatty acid synthase and stearoyl CoA desaturase-1 (SCD-1) mRNA levels and SCD-1 index along with significantly lower sterol regulatory element binding protein-1 mRNA, a transcription factor that regulates lipogenesis. Furthermore, the lower lipogenesis was associated with significantly higher mRNA expression of lipid oxidation gene peroxisome proliferator-activated receptor-alpha and acetyl CoA oxidase in the livers of rats fed dietary CLA. The lipid-lowering effects of CLA in the liver were observed in the absence of changes in adipose tissue and body weight. Thus, we conclude that in the Wistar rat model, where adipose levels remain static after feeding dietary CLA, hepatic lipid accumulation is reduced and these effects are not due to an improvement in overall adiposity. PMID:17368879

Purushotham, Aparna; Shrode, Gayle E; Wendel, Angela A; Liu, Li-Fen; Belury, Martha A

2007-10-01

118

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

PubMed Central

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

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

2010-01-01

119

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

PubMed Central

Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in e Marchigian Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced gray matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn gray matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction. PMID:23261637

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

2014-01-01

120

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

PubMed

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

Diogo, Rui; Molnar, Julia

2014-06-01

121

Molecular cloning of the Notophthalmus viridescens radical fringe cDNA and characterization of its expression during forelimb development and adult forelimb regeneration.  

PubMed

Larval and adult newts provide important experimental models to study limb development and regeneration. These animals have exceptional ability to regenerate their appendages, as well as other vital structures. Our research examines the role of the fringe gene (fng) in the developing and regenerating adult newt forelimb. Fringe codes for a secretory protein. It was first discovered in Drosophila, and later homologues were isolated in Xenopus laevis, chick and mouse. This gene has been highly conserved throughout evolution, indicating its crucial role in vertebrate and invertebrate development. We have isolated, cloned, and sequenced the full length of the Notophthalmus viridescens radical fringe cDNA (nrFng) by screening a newt forelimb blastema cDNA library with a 500-bp fragment of the Xenopus lunatic fringe cDNA. The newt fringe cDNA codes for a 396 amino acid protein with a predicted N-terminal signal sequence. Newt fringe shows high homology with radical fringe homologues of many species. Whole mount mRNA in situ hybridization on several stages of newt limb development reveals that nrFng is first expressed in the limb field, with intense expression as the limb bud develops. However, gene expression diminishes with more advanced digit development. A significant role in adult forelimb regeneration is also evident, as we isolated the cDNA from a regeneration-specific library and found it highly expressed during the regenerative phases of active cell division and then down regulated at sites undergoing differentiation and morphogenesis. PMID:10090152

Cadinouche, M Z; Liversage, R A; Muller, W; Tsilfidis, C

1999-03-01

122

CD47 Blockade Reduces Ischemia Reperfusion Injury and Improves Survival in a Rat Liver Transplantation Model.  

PubMed

Orthotopic liver transplantation (OLT) remains the standard treatment option for non-responsive liver failure. Given that ischemia reperfusion injury (IRI) is an important impediment to the success of OLT, new therapeutic strategies are needed to reduce IRI. We investigated whether blocking the CD47/TSP-1 inhibitory action on NO signaling using a monoclonal antibody specific to CD47 (CD47mAb400) reduces IRI in liver grafts. Syngeneic OLT was performed using Lewis rats. Control IgG or CD47mAb400 was administered to the donor organ at procurement or to both the organ and the recipient at the time of transplant. Serum transaminases, histological changes of the liver and animal survival were assessed. Oxidative stress, inflammatory responses and hepatocellular damage were also quantified. A significant survival benefit was not achieved when CD47mAb400 was administered to the donor alone. However, CD47mAb400 administration to both the donor and recipient increased animal survival after. The CD47mAb400 treated group showed lower serum transaminases, bilirubin, oxidative stress, TUNEL staining, caspase-3 activity and proinflammatory cytokine expression of TNF-?, IL-1? and IL-6. Thus CD47 blockade with CD47mAb400 administered both to the donor and the recipient reduced liver graft IRI in a rat liver transplantation model. This may translate to decreased liver dysfunction and increased survival of liver transplant recipients. This article is protected by copyright. All rights reserved. PMID:25482981

Xiao, Zhen-Yu; Banan, Babak; Jia, Jianluo; Manning, Pamela T; Hiebsch, Ronald R; Gunasekaran, Muthukumar; Upadhya, Gundumi A; Frazier, William A; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William C

2014-12-01

123

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat  

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

124

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

PubMed

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

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

2012-02-01

125

Agmatine reduces ultrasonic vocalization deficits in female rat pups exposed neonatally to ethanol.  

PubMed

Rat pups, in isolation, produce ultrasonic vocalizations (USVs). These USVs have been used as a diagnostic tool for developmental toxicity. We have shown that neonatal ethanol (ETOH) exposure produces deficits in this behavior. The current study was designed to examine whether agmatine (AG), which binds to imidazoline receptors and modulates n-methyl-d-aspartate receptors (NMDAR), could reduce these deficits. In addition, this study examined critical periods for ETOH's effects on USVs by administering ETOH during either the 1st or 2nd postnatal week. Neonatal rats received intragastric intubations of either ETOH (6g/kg/day), ETOH and AG (6g/kg/day and 20mg/kg/day), AG (20mg/kg/day), or maltose on postnatal days (PND) 1-7 or 8-14. A non-intubated control was also included. Subjects were tested on PND 15. Neonatal ETOH exposure significantly increased the latency to vocalize for females and reduced the rate of USVs in both males and females exposed to ETOH on PND 1-7. Agmatine reduced these deficits, in female but not male pups. Subjects exposed to ETOH on PND 8-14 showed no evidence of abnormal USVs. These findings suggest that there may be gender differences in response to AG following neonatal ETOH exposure and also provide further support that the first neonatal week is a particularly sensitive time for the developmentally toxic effects of ETOH in rodents. PMID:19945529

Wellmann, Kristen; Lewis, Ben; Barron, Susan

2010-01-01

126

Vagus Nerve Stimulation Reduces Body Weight and Fat Mass in Rats  

PubMed Central

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

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

127

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

PubMed Central

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

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

2013-01-01

128

Cryotherapy reduces skeletal muscle damage after ischemia/reperfusion in rats  

PubMed Central

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

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

129

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

PubMed

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

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

2009-10-01

130

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

PubMed Central

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

Bhattacharya, Koushik; Mukherjee, Soumya

2014-01-01

131

Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats.  

PubMed

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor-alpha and its target genes, 7-alpha hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and delta5 and delta6 desaturases, decreasing lipogenesis even in the presence of hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes, preventing hypertrophy, which also helps prevent the development of hepatic lipotoxicity. PMID:15995177

Tovar, Armando R; Torre-Villalvazo, Ivan; Ochoa, Melissa; Elías, Ana L; Ortíz, Victor; Aguilar-Salinas, Carlos A; Torres, Nimbe

2005-09-01

132

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

PubMed

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

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

2014-01-01

133

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

PubMed Central

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

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

2013-01-01

134

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

PubMed

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

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

2015-01-01

135

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

PubMed

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

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

2015-01-01

136

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

PubMed

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

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

2008-02-28

137

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

PubMed

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

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

138

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

PubMed

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

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

2013-02-01

139

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

E-print Network

of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area & Wood, 2011). How- ever, forelimb muscle architecture (muscle mass, fascicle length and physiological cross-sectional area) has been stud- ied to a lesser extent and in fewer species (e.g. chimpanzee

D'Août, Kristiaan

140

Forelimb regeneration in thyroidectomized adult newts following organ culture and autografting of the thyroid glands  

Microsoft Academic Search

Thyroidectomy and organ culture of adult newt thyroid glands three days prior to forelimb amputation was followed by autografting the glands subcutaneously into the animal's lower jaw region 9, 18 or 25 days postamputation (GC9, 18, 25 day series). This was an attempt, utilizing 515 animals, to elucidate further the role of the thyroids in regeneration. Amputated limbs of the

Richard A. Liversage; Pauline J. Brandes

1982-01-01

141

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

PubMed

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

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

142

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

PubMed Central

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

2014-01-01

143

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

PubMed

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

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

2014-10-29

144

Exercise to reduce the escalation of cocaine self-administration in adolescent and adult rats  

PubMed Central

Rationale Concurrent access to an exercise wheel decreases cocaine self-administration under short access (5 h/day for 5 days) conditions and suppresses cocaine-primed reinstatement in adult rats. Objective The effect of exercise (wheel running) on the escalation of cocaine intake during long access (LgA, 6 h/day for 26 days) conditions was evaluated. Methods Adolescent and adult female rats acquired wheel running, and behavior was allowed to stabilize for 3 days. They were then implanted with an iv catheter and allowed to self-administer cocaine (0.4 mg/kg, iv) during 6-h daily sessions for 16 days with concurrent access to either an unlocked or a locked running wheel. Subsequently, for ten additional sessions, wheel access conditions during cocaine self-administration sessions were reversed (i.e., locked wheels became unlocked and vice versa). Results In the adolescents, concurrent access to the unlocked exercise wheel decreased responding for cocaine and attenuated escalation of cocaine intake irrespective of whether the locked or unlocked condition came first. However, cocaine intake increased when the wheel was subsequently locked for the adolescents that had initial access to an unlocked wheel. Concurrent wheel access either before or after the locked wheel access did not reduce cocaine intake in adults. Conclusions Wheel running reduced cocaine intake during LgA conditions in adolescent but not adult rats, and concurrent access to the running wheel was necessary. These results suggest that exercise prevents cocaine seeking and that this effect is more pronounced in adolescents than adults. PMID:22752381

Anker, Justin J.; Carroll, Marilyn E.

2013-01-01

145

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

PubMed Central

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

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

2014-01-01

146

Contralateral treatment with lidocaine reduces spinal neuronal activity in mononeuropathic rats.  

PubMed

In anaesthetised and paralysed rats with chronic constriction of the sciatic nerve, the effects of subcutaneous contralateral lidocaine (100 microl) on the activity of lumbar (L(4)-L(5)) wide dynamic range neurons ipsilateral to the constriction have been investigated. The results show reduction of the spontaneous hyperactivity for 60 min; suppression or reduction of the responses to contralateral noxious stimulation for 60 min; lack of effect on the responses to ipsilateral noxious stimulation, except for the afterdischarge duration, reduced for 60 min. The finding that the altered neuronal activity following peripheral nerve injury associated to behavioural signs of neuropathic pain, can be reduced by contralateral treatment, may provide further suggestions to neuropathic pain mechanisms and management. PMID:11578818

Bileviciute-Ljungar, I; Biella, G; Bellomi, P; Sotgiu, M L

2001-10-01

147

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

PubMed Central

Preeclampsia is defined as new-onset hypertension with proteinuria after 20 wk gestation and is hypothesized to be due to shallow trophoblast invasion in the spiral arteries thus resulting in progressive placental ischemia as the fetus grows. Many animal models have been developed that mimic changes in maternal circulation or immune function associated with preeclampsia. The model of reduced uterine perfusion pressure in pregnant rats closely mimics the hypertension, immune system abnormalities, systemic and renal vasoconstriction, and oxidative stress in the mother, and intrauterine growth restriction found in the offspring. The model has been successfully used in many species; however, rat and primate are the most consistent in comparison of characteristics with human preeclampsia. The model suffers, however, from lack of the ability to study the mechanisms responsible for abnormal placentation that ultimately leads to placental ischemia. Despite this limitation, the model is excellent for studying the consequences of reduced uterine blood flow as it mimics many of the salient features of preeclampsia during the last weeks of gestation in humans. This review discusses these features. PMID:22523250

Li, Jing; LaMarca, Babbette

2012-01-01

148

Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites hepatoma cells.  

PubMed

Autophagy, measured as the sequestration of an endogenous cytosolic enzyme (LDH), showed a progressive rate reduction during diethylnitrosamine-induced rat liver carcinogenesis. In primary hepatocellular carcinomas the autophagic activity was only one-fourth of that seen in normal hepatocytes. Reduced autophagy was also observed in peritumorous hepatocytes and in cells from preneoplastic liver, and a complete suppression of autophagic protein degradation was seen in normal hepatocytes treated with ascitic fluid from an ascites hepatoma, suggesting that tumour cells and their precursors may produce autophagy-suppressive factors with an autocrine and paracrine action. In cells from the transplantable rat ascites hepatoma, Yoshida AH-130, autophagic activity was negligible during active (logarithmic) growth, but increased to approximately 0.4%/h at high cell density, i.e. in stationary phase. In contrast to normal hepatocytes, autophagy in the AH-130 cells was not inhibited by ascitic fluid. The hepatoma cells would thus appear to have lost some aspects of autophagy regulation while retaining others. However, even the highest rate of hepatoma cell autophagy was only one-tenth of the maximal activity seen in normal hepatocytes, confirming the hypothesis that reduced autophagy may be an important aspect of growth deregulation in liver cancer. PMID:8269618

Kisen, G O; Tessitore, L; Costelli, P; Gordon, P B; Schwarze, P E; Baccino, F M; Seglen, P O

1993-12-01

149

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

SciTech Connect

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

Wilkes, B.M.

1987-04-01

150

Does increased endogenous CCK interact with serotonin to reduce food intake in rats?  

PubMed

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake. PMID:11150652

Voigt, J P; Wenz, D; Voits, M; Fink, H

2000-12-01

151

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

PubMed

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

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

2014-12-01

152

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

PubMed Central

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

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

2014-01-01

153

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

PubMed Central

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

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

2014-01-01

154

Radiographs Reveal Exceptional Forelimb Strength in the Sabertooth Cat, Smilodon fatalis  

PubMed Central

Background The sabertooth cat, Smilodon fatalis, was an enigmatic predator without a true living analog. Their elongate canine teeth were more vulnerable to fracture than those of modern felids, making it imperative for them to immobilize prey with their forelimbs when making a kill. As a result, their need for heavily muscled forelimbs likely exceeded that of modern felids and thus should be reflected in their skeletons. Previous studies on forelimb bones of S. fatalis found them to be relatively robust but did not quantify their ability to withstand loading. Methodology/Principal Findings Using radiographs of the sabertooth cat, Smilodon fatalis, 28 extant felid species, and the larger, extinct American lion Panthera atrox, we measured cross-sectional properties of the humerus and femur to provide the first estimates of limb bone strength in bending and torsion. We found that the humeri of Smilodon were reinforced by cortical thickening to a greater degree than those observed in any living felid, or the much larger P. atrox. The femur of Smilodon also was thickened but not beyond the normal variation found in any other felid measured. Conclusions/Significance Based on the cross-sectional properties of its humerus, we interpret that Smilodon was a powerful predator that differed from extant felids in its greater ability to subdue prey using the forelimbs. This enhanced forelimb strength was part of an adaptive complex driven by the need to minimize the struggles of prey in order to protect the elongate canines from fracture and position the bite for a quick kill. PMID:20625398

Meachen-Samuels, Julie A.; Van Valkenburgh, Blaire

2010-01-01

155

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

PubMed

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

Burch, Sara H

2014-09-01

156

Housing familiar male wildtype rats together reduces the long-term adverse behavioural and physiological effects of social defeat.  

PubMed

Social stress in rats is known to induce long-lasting, adverse changes in behaviour and physiology, which seem to resemble certain human psychopathologies, such as depression and anxiety. The present experiment was designed to assess the influence of individual or group housing on the vulnerability of male Wildtype rats to long-term effects of inescapable social defeat. Group-housed rats were individually exposed to an aggressive, unfamiliar male conspecific, resulting in a social defeat. Defeated rats were then either individually housed or returned to their group. The changes in their behaviour and physiology were then studied for 3 weeks. Results showed that individually housed rats developed long-lasting, adverse behavioural and physiological changes after social defeat. Their body growth was significantly retarded (p < .05) between 7 and 14 days after defeat. When individually and group-housed rats were exposed to a mild stressor (sudden silence) 2 days after defeat, both groups became highly immobile. However, when exposure was repeated at day 21, individually housed rats were still highly immobile compared to group-housed rats which regained their normal mobility after only 7 days. In an open field test, also regularly repeated, individually housed rats took significantly longer to leave their home base and were also significantly less mobile than group-housed rats over the entire 3-week test period as well as at specific timepoints. When the rats were placed in an elevated plus-maze 14 days after defeat, those that were individually housed were significantly more anxious than those that were group-housed. When tested at 21 days after defeat in a combined dexamethasone (DEX)/corticotrophin-releasing factor (CRF) test, results showed that the hypothalamic-pituitary-adrenocortical (HPA) activity in individually housed rats was higher. This was evidenced in the latter animals by the fact that DEX was significantly less able to suppress the secretion of ACTH and corticosterone, and by a significantly higher release of ACTH after administration of CRF. Although the weights of the spleen and testes of the two groups did not differ, the adrenals of individually housed rats were larger and the thymus and seminal vesicles were smaller. We conclude that when rats are isolated after defeat, they show long-lasting, adverse behavioural and physiological changes that resemble symptoms of stress-related disorders. In contrast, when familiar rats are housed together these effects of a social defeat are greatly reduced. These findings show that housing conditions importantly influence the probability of long-term adverse behavioural and physiological effects of social defeat in male Wildtype rats. PMID:10101734

Ruis, M A; te Brake, J H; Buwalda, B; De Boer, S F; Meerlo, P; Korte, S M; Blokhuis, H J; Koolhaas, J M

1999-04-01

157

Dexmedetomidine Reduces Response Tendency, but Not Accuracy of Rats in Attention and Short-Term Memory Tasks  

Microsoft Academic Search

The present study investigated the role of ?2-adrenergic mechanisms in the performance of motor responses, attention and short-term memory in rats. A low dose (3.0 ?g\\/kg, s.c.) of dexmedetomidine, an ?2-adrenoceptor agonist, reduced response tendency in an attentional task and a working memory task, but it did not affect the choice accuracy of rats. Atipamezole (300 ?g\\/kg), an ?2-adrenoceptor antagonist,

Sirja Ruotsalainen; Antti Haapalinna; Paavo J. Riekkinen; Jouni Sirviö

1997-01-01

158

Melatonin reduces bacterial translocation by preventing damage to the intestinal mucosa in an experimental severe acute pancreatitis rat model  

PubMed Central

Recent studies have demonstrated that melatonin significantly decreased all studied acute pancreatitis-associated inflammatory parameters, in addition to reducing apoptosis and necrosis associated with pancreatic injury. However, the effect of melatonin on gut barrier dysfunction and bacterial translocation has not been fully elucidated. This study aimed to investigate the protective effects of melatonin on intestinal integrity in a rat model of severe acute pancreatitis (SAP) to evaluate whether melatonin prevented intestine barrier dysfunction and reduced bacterial translocation. Forty male Sprague Dawley (SD) rats were randomly divided into three groups, with 8 rats in the sham operation (SO) group, 18 rats in the SAP group and 14 SAP rats in the melatonin treatment (MT) group. SAP was induced by retrograde injection of 4% taurocholate into the biliopancreatic duct. Melatonin was administered 30 min prior to taurocholate injection in the melatonin-treated rats. All rats were sacrificed 24 h subsequent to pancreatitis induction. Real-time fluorescence quantitative polymerase chain reaction was used to detect and quantify Escherichia coli (E. coli) O157 in postcava blood. The microvilli structure was also analyzed with transmission electron microscopy. The level of E. coli DNA in the MT group was significantly lower than in rats in the SAP group. No E. coli DNA was detected in the control group. Villus height and crypt depth in the ileum were significantly higher in the MT and control groups compared to the SAP group, and were significantly higher in the MT group than in the SAP group. These results suggested that melatonin prevented gut barrier dysfunction and reduced bacterial translocation, resulting in reduced pancreatic-associated infections and decreased early mortality rates. PMID:24255660

SUN, XUECHENG; SHAO, YINGYING; JIN, YIN; HUAI, JIAPING; ZHOU, QIONG; HUANG, ZHIMING; WU, JIANSHENG

2013-01-01

159

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

PubMed

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

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

2013-08-01

160

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

PubMed Central

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

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

2013-01-01

161

Acute administration of ethanol reduces apoptosis following ischemic stroke in rats.  

PubMed

In recent studies, acute ethanol administration appears to play a neuroprotective role during ischemic stroke. We sought to confirm these findings by identifying if ethanol-derived neuroprotection is associated with a reduction in apoptosis. Ethanol at 0.5 and 1.5 g/kg doses was given by intraperitoneal injections to Sprague-Dawley rats after 2h of middle cerebral artery (MCA) occlusion, followed by reperfusion. We quantified apoptotic cell death in each of the treatment groups with ELISA, and measured pro- and anti-apoptotic protein expression with Western blot analysis. Cell death was significantly increased in rats after ischemia and was subsequently significantly reduced by the administration of 1.5 g/kg of ethanol. We found that the 1.5 g/kg dose promoted the expression of pro-survival factors and decreased the expression of apoptotic proteins at 3h after reperfusion. This effect was maintained at 24h for Caspase-3 and apoptosis-inducing factor (AIF), although not for Bcl-2, Bcl-xL, and Bcl-2-associated X (Bax). Administration of 0.5 g/kg of ethanol was not as effective in regulating protein expression as the 1.5 g/kg dose. Our study suggests that administration of ethanol at a dose of 1.5 g/kg after stroke - which provides rat blood alcohol levels equivalent to the legal driving limit - produces a differential protein profile, with increased expression of anti-apoptotic proteins and decrease in pro-apoptotic factors. This results in a significant reduction of neuronal apoptosis and is neuroprotective in ischemia-reperfusion injury. PMID:23511554

Fu, Paul; Peng, Changya; Ding, Jamie Y; Asmaro, Karam; Sullivan, Jonathon M; Guthikonda, Murali; Ding, Yuchuan

2013-01-01

162

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

PubMed Central

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads. PMID:24106408

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

2013-01-01

163

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

PubMed Central

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

Rörig, B; Klausa, G; Sutor, B

1996-01-01

164

SDF-1? in Glycan Nanoparticles Exhibits Full Activity and Reduces Pulmonary Hypertension in Rats  

PubMed Central

In order to establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1? NP, by complexing SDF-1? with dextran sulfate and chitosan. The data show that SDF-1? was barely released from the nanoparticles over an extended period of time in vitro (3% in 7 days at 37°C); however, incorporated SDF-1? exhibited full chemotactic activity and receptor activation compared to its free form. The nanoparticles were not endocytosed after incubation with Jurkat cells. When aerosolized into the lungs of rats, SDF-1? NP displayed a greater retention time compared to free SDF-1? (64% vs. 2% remaining at 16 hr). In a rat model of monocrotaline-induced lung injury, SDF-1? NP, but not free form SDF-1?, was found to reduce pulmonary hypertension. These data suggest that the nanoparticle formulation protected SDF-1? from rapid clearance in the lung and sustained its biological function in vivo. PMID:24059347

Yin, Tao; Bader, Andrew R.; Hou, Tim K.; Maron, Bradley A.; Kao, Derrick D.; Qian, Ray; Kohane, Daniel S.; Handy, Diane E.; Loscalzo, Joseph; Zhang, Ying-Yi

2013-01-01

165

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

PubMed Central

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

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

166

Effect of reduced ovarian tissue on cyclicity, basal hormonal levels and follicular development in old rats.  

PubMed

Reduction of the number of growing follicles was proposed to contribute to the decline in reproductive performance with aging (Butcher and Page, 1981). To investigate the effects of a reduced number of follicles, rats which maintained regular estrous cycles at greater than 1 yr of age had either unilateral ovariectomy (ULO) or control surgery. Irregular estrous cycles and periods of constant estrus were more frequent during a period of 90 days after ULO than in controls. Follicle-stimulating hormone (FSH) concentration in plasma collected at 0900-1100 h of the metestrus nearest to 20, 50, and 90 days after surgery was increased by ULO; in both treatment groups, FSH increased between 20 and 90 days. Compensation in ovarian weight and number of corpora lutea had occurred by 90 days after ULO. Estradiol, estrone and luteinizing hormone (LH) concentrations did not change with time or treatment. Numbers of small, medium and large antral follicles per ovary at metestrus were increased by ULO, while the number of follicles per rat was decreased. It was concluded that the reduction in ovarian tissue (which decreased the number of growing follicles) resulted in an elevation of basal FSH followed by irregularity in estrous cycles. PMID:3921071

Butcher, R L

1985-03-01

167

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain.  

PubMed

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia. PMID:7860651

Hasegawa, Y; Latour, L L; Formato, J E; Sotak, C H; Fisher, M

1995-03-01

168

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

SciTech Connect

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.

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

1989-01-01

169

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

PubMed Central

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

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

2014-01-01

170

Synthetic peptide TPLVTLFK (octarphin) reduces the corticosterone production by rat adrenal cortex through nonopioid ?-endorphin receptor.  

PubMed

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12-19 of ?-endorphin, a selective agonist of nonopioid ?-endorphin receptor, was labeled with tritium to a specific activity of 29 Ci/mmol. [(3)H]Octarphin was found to bind to high-affinity naloxone-insensitive binding sites on membranes isolated from rat adrenal cortex (K(d) = 35.7 ± 2.3 nM, B(max) = 41.0 ± 3.6 pmol/mg protein). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but to ?-endorphin, ?-endorphin, [Met(5) ]enkephalin, and [Leu(5) ]enkephalin as well. At the same time, the [(3) H]octarphin-specific binding with adrenal cortex membranes was inhibited by unlabeled ?-endorphin (K(i) = 32.9 ± 3.8 nM). Octarphin at concentrations of 10(-9) -10(-6) M was found to inhibit the adenylate cyclase activity in adrenocortical membranes, whereas intranasal injection of octarphin at doses of 5 and 20 µg/rat was found to reduce the secretion of corticosterone from the adrenals to the bloodstream. Thus, octarphin decreases the adrenal cortex functional activity through the high affinity binding to nonopioid receptor of ?-endorphin. PMID:22744732

Nekrasova, Yuliia N; Zolotarev, Yury A; Navolotskaya, Elena V

2012-08-01

171

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

PubMed

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-cm(3) 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

Atilgan, Dogan; Parlaktas, Bekir; Uluocak, Nihat; Gencten, Yusuf; Erdemir, Fikret; Ozyurt, Huseyin; Erkorkmaz, Unal; Aslan, Huseyin

2014-08-01

172

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

PubMed Central

The present study aimed to evaluate the effect of pomegranate juice (PJ) on oxidative stress (OS) and sperm concentration in a rat model of testicular torsion-detorsion. A total of 21 Wistar albino rats were randomly divided into three groups, each consisting of seven rats, as follows: i) control group, which underwent sham surgery; ii) ischemia/reperfusion (I/R) group, designed to determine the effects of the testicular torsion-detorsion process on rats; and iii) PJ+I/R group, designed to evaluate the effect of PJ on the OS and sperm cell concentrations induced by the torsion-detorsion process. In the PJ+I/R group, the rats were given 0.4 ml/day PJ orally over a period of eight weeks prior to surgery. Ipsilateral orchiectomy was carried out and 5-cm3 blood samples were obtained from the inferior vena cava of all rats. Biochemical analyses were performed to calculate the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the testicular tissue and serum. The concentrations of spermatids, spermatocytes and spermatogonia in the seminiferous tubules were assessed using histopathological methods. Serum and tissue SOD and MDA levels were significantly higher in rats from the I/R group compared with the control group (P<0.001). PJ treatment significantly decreased the SOD and MDA levels in both the serum and testicular tissue of the rats (P<0.001). The spermatid, spermatocyte and spermatogonia concentrations were significantly reduced in the I/R group compared with the control group (P<0.001). PJ treatment significantly improved the concentrations of spermatids, spermatocytes and spermatogonia compared with those in the I/R group (P=0.008). The experimentally established testicular torsion-detorsion model led to OS in the rat testes. Daily consumption of PJ prior to surgery reduced OS parameters and improved sperm cell concentrations. PMID:25009604

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

2014-01-01

173

Dietary soy protein reduces early renal disease progression and alters prostanoid production in obese fa/fa Zucker rats.  

PubMed

With the rising incidence of obesity and the metabolic syndrome, obesity-associated nephropathy also has increased. One of the earliest pathologies in the development of this nephropathy is glomerular hyperfiltration and hypertrophy. Dietary soy protein (SP) ameliorates disease progression in several models of renal disease, and vegetable sources of protein, as compared to animal sources of protein, alter renal hemodynamics. Therefore, the effect of dietary SP on early renal disease and prostanoid production was examined in the obese fa/fa Zucker rat. Rats, 6 weeks of age, were given diets containing 17% protein from either SP or egg white (EW) for 8 weeks. Feed consumption and body and kidney weights were significantly greater in fa/fa rats as compared to lean rats. The fa/fa rats also had 139% more proteinuria and kidneys with 43% larger glomeruli. SP feeding did not alter body weights or proteinuria but did result in 6% lower kidney weights (g/100 g body weight) and 16% smaller glomeruli in fa/fa rats. Cyclooxygenase activity as determined by 6-keto prostaglandin F(1alpha) (6-keto PGF(1alpha)) synthesis was lower in fa/fa rats given SP-based diets as compared to those given EW-based diets. Ratios of renal thromboxane (TX) B(2)/6-keto PGF(1alpha) and PGE(2)/6-keto PGF(1alpha) were higher, while TXB(2)/PGE(2) levels were not different in rats given SP diets as compared to those given EW diets, also indicating that dietary SP reduced renal 6-keto PGF(1alpha) levels. These findings suggest that attenuation of early glomerular hypertrophy in young obese fa/fa rats by dietary SP may be mediated by the lower levels of 6-keto PGF(1alpha) since this would be expected to reduce glomerular hyperfiltration. PMID:17656081

Hwang, Sun-Young; Taylor, Carla G; Zahradka, Peter; Bankovic-Calic, Neda; Ogborn, Malcolm R; Aukema, Harold M

2008-04-01

174

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

PubMed Central

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

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

2008-01-01

175

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

PubMed Central

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

2013-01-01

176

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

PubMed

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

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

2014-10-15

177

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

PubMed Central

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

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

178

A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats.  

PubMed

In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague-Dawley rats for 2h. Either CM (30, 100 and 300mg/kg) or saline was intragastrically administrated to the rats 30min before the acute restraint stress. Visceral perception was quantified as visceral motor response with an electromyography in a subset of rats. Paracellular permeability was determined in another subset of rats. We found that the visceral sensitivity and paracellular permeability were significantly reduced in the CM-treated rats. Moreover, the fecal protease activity was decreased in the CM-treated rats. The ZO-1 protein expression was markedly reduced by the stress treatment, but this decrease was suppressed by CM administration. Our data indicated that CM could efficiently inhibit visceral sensitivity and paracellular permeability induced by the acute restraint stress in rats. Therefore, CM might be an effective drug for the treatment of irritable bowel syndrome. PMID:21237151

Zhao, Juhui; Wang, Jinhai; Dong, Lei; Shi, Hongyang; Wang, Zongyan; Ding, Hui; Shi, Haitao; Lu, Xiaolan

2011-03-11

179

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

PubMed

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

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

2008-08-01

180

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

PubMed Central

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

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

2011-01-01

181

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

PubMed Central

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

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

2013-01-01

182

Lactate per se improves the excitability of depolarized rat skeletal muscle by reducing the Cl? conductance  

PubMed Central

Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl? channels. However, since several carboxylic acids with structural similarities to lactate can inhibit muscle Cl? channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined the effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl? conductance (Gcl). In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by (mean ±s.e.m.) 82 ± 4% and 83 ± 2%, respectively, by depolarization with 11 mm extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mm lactate was added. This effect was present already at 5 mm and saturated at 15 mm lactate, and was associated with a 31% reduction in GCl. The effects of lactate were completely blocked by Cl? channel inhibition or use of Cl?-free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl? channels and increase the excitability and contractile function of depolarized rat muscles via mechanisms not related to a reduction in intracellular pH. PMID:20876199

de Paoli, Frank Vincenzo; Ørtenblad, Niels; Pedersen, Thomas Holm; Jørgensen, Rasmus; Nielsen, Ole Bækgaard

2010-01-01

183

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

PubMed

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

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

2014-11-16

184

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

USGS Publications Warehouse

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

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

2013-01-01

185

Acetylpuerarin reduces inflammation and improves memory function in a rat model of Alzheimer's disease induced by Abeta1-42.  

PubMed

This study was performed to determine if acetylpuerarin (compound N-2211) could reduce amyloid-beta1-42 (Abeta1-42) induced learning and memory deficits and to examine its anti-neuroinflammatory effects in a rat model. Forty Wistar rats were randomly divided into four groups (n = 10 each): control, model (Abeta1-42 injected), low-dose and high-dose acetylpuerarin groups. The acetylpuerarin groups received peritoneal acetylpuerarin every day for 12 days after 2 weeks of Abeta1-42 (5 microg/1 microl) intrahippocampal injections. The Morris water maze (MWM) was used to assess rats' learning and memory abilities. Immunohistochemistry was used to assess expression levels of ionized calcium-binding adaptor molecule (Ibal), protein kinase C delta (PKCdelta), IkappaB kinase beta (IKKbeta), and inducible nitric oxide synthase (iNOS) in hippocampus. After Abeta1-42 injection, the learning and memory abilities of rats were reduced, and acetylpuerarin treatment ameliorated the observed deficits. Abeta1-42 injection resulted in microglia transforming from resting microglia into an activated state, but this was reduced by acetylpuerarin treatment. Furthermore, hippocampal expression of PKCdelta, IKKbeta, and iNOS increased following Abeta1-42 treatment, and acetylpuerarin could suppressed the levels of PKCdelta, iNOS, and IKKbeta. Acetylpuerarin improves learning and memory functions in Abeta1-42 induced rat models. These effects may be due to anti-neuroinflammatory effects. PMID:24380241

Meng, Q H; Lou, F L; Hou, W X; Liu, M; Guo, H; Zhang, X M

2013-11-01

186

Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury  

NASA Astrophysics Data System (ADS)

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

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

2013-06-01

187

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

PubMed Central

A detailed musculoskeletal model of the distal equine forelimb was developed to study the influence of musculoskeletal geometry (i.e. muscle paths) and muscle physiology (i.e. force–length properties) on the force- and moment-generating capacities of muscles crossing the carpal and metacarpophalangeal joints. The distal forelimb skeleton was represented as a five degree-of-freedom kinematic linkage comprised of eight bones (humerus, radius and ulna combined, proximal carpus, distal carpus, metacarpus, proximal phalanx, intermediate phalanx and distal phalanx) and seven joints (elbow, radiocarpal, intercarpal, carpometacarpal, metacarpophalangeal (MCP), proximal interphalangeal (pastern) and distal interphalangeal (coffin)). Bone surfaces were reconstructed from computed tomography scans obtained from the left forelimb of a Thoroughbred horse. The model was actuated by nine muscle–tendon units. Each unit was represented as a three-element Hill-type muscle in series with an elastic tendon. Architectural parameters specifying the force-producing properties of each muscle–tendon unit were found by dissecting seven forelimbs from five Thoroughbred horses. Maximum isometric moments were calculated for a wide range of joint angles by fully activating the extensor and flexor muscles crossing the carpus and MCP joint. Peak isometric moments generated by the flexor muscles were an order of magnitude greater than those generated by the extensor muscles at both the carpus and the MCP joint. For each flexor muscle in the model, the shape of the maximum isometric joint moment–angle curve was dominated by the variation in muscle force. By contrast, the moment–angle curves for the muscles that extend the MCP joint were determined mainly by the variation in muscle moment arms. The suspensory and check ligaments contributed more than half of the total support moment developed about the MCP joint in the model. When combined with appropriate in vivo measurements of joint kinematics and ground-reaction forces, the model may be used to determine muscle–tendon and joint–reaction forces generated during gait. PMID:12892409

Brown, Nicholas AT; Pandy, Marcus G; Kawcak, Christopher E; Mcllwraith, C Wayne

2003-01-01

188

Hox C6 expression during development and regeneration of forelimbs in larval Notophthalmus viridescens  

Microsoft Academic Search

A central theme concerning the epimorphic regenerative potential of urodele amphibian appendages is that limb regeneration\\u000a in the adult parallels larval limb development. Results of previous research have led to the suggestion that homeobox containing\\u000a genes are ”re-expressed” during the epimorphic regeneration of forelimbs of adult Notophthalmus viridescens in patterns which retrace larval limb development. However, to date no literature

Paul A. Khan; Catherine Tsilfidis; Richard A. Liversage

1999-01-01

189

Effects of reduced vesicular filling on synaptic transmission in rat hippocampal neurones  

PubMed Central

The consequence of reduced uptake of neurotransmitters into synaptic vesicles on synaptic transmission was examined in rat hippocampal slices and culture using bafilomycin A1 (Baf), a potent and specific blocker of the vacuolar-type (V-type) ATPase, which eliminates the driving force for the uptake of both glutamate and GABA into synaptic vesicles. After incubation with Baf, both the amplitude and frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were reduced in the slice preparation. Similar effects were seen with glutamatergic miniature excitatory postsynaptic currents (mEPSCs) and GABAergic mIPSCs from cultured neurons. This result indicates that vesicular content is reduced by Baf. The dramatic reduction in the frequency of mPSCs could result either from the exocytosis of empty vesicles or from a mechanism which prevents the exocytosis of depleted vesicles. Vesicle cycling was directly examined using confocal imaging with FM 1–43. In the presence of Baf, vesicles could still be endocytosed and they were released at the same probability as from control untreated synapses. Prolonged high-frequency electrical stimulation of synapses in culture failed to alter the amplitude of mEPSCs, suggesting that the filling of vesicles is rapid compared to the rate of vesicle recycling during repetitive synaptic stimulation. Profound release of glutamate with ?-latrotoxin did cause a small, but reproducible, reduction in quantal size. These results indicate that decreasing the amount of glutamate and GABA in synaptic vesicles reduces quantal size. Furthermore, the probability of vesicle exocytosis appears to be entirely independent of the state of filling of the vesicle. However, even during high-frequency action potential-evoked release of glutamate, quantal size remained unchanged. PMID:10811737

Zhou, Qiang; Petersen, Carl C H; Nicoll, Roger A

2000-01-01

190

Chronic morphine reduces pain-related disability in a rodent model of chronic, inflammatory pain.  

PubMed

Chronic pain is disabling, and the adverse effects of morphine are also disabling. The best way to assess the beneficial effects relative to the potential adverse effects of chronic morphine may be through the use of quantitative measures of functional disability in people and animals experiencing pain. If chronic morphine alleviates chronic pain and its beneficial analgesic effects outweigh whatever adverse effects it may produce, then it should reduce pain-related disability. Rats with adjuvant-induced arthritis were implanted with subcutaneous morphine pellets. Continuous morphine reduced pain-related disability in tasks motivated by food reward or shock avoidance throughout the 35 days of continuous administration--first, in tests that primarily assessed the function of the less severely affected forelimbs, and later, as the inflammation subsided, in tests more dependent on the function of the more severely affected hind limbs. PMID:10472506

Lindner, M D; Plone, M A; Francis, J M; Cain, C K

1999-08-01

191

Humoral factor(s) circulating in the blood of spontaneously hypertensive rats increases vascular tone and reduces constrictive responses of isolated rat caudal artery to stimulation of sympathetic fibers of the vascular wall  

Microsoft Academic Search

It is shown that the perfusion pressure in isolated rat caudal artery rises and constrictive responses to electrical stimulation\\u000a decrease when the blood of normotensive Wistar-Kyoto rats perfusing the vessel was replaced by the blood of spontaneously\\u000a hypertensive rats. The norepinephrine release from the sympathetic terminals is reduced.

N. A. Medvedeva; M. A. Zharkova; A. A. Chuiko; O. S. Medvedev

1996-01-01

192

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

PubMed Central

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

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

2013-01-01

193

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

PubMed Central

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

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

2009-01-01

194

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

PubMed Central

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

Fujiwara, Shin-ichi; Hutchinson, John R.

2012-01-01

195

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

PubMed Central

The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The “proarrhythmic” effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T1-T4), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias. PMID:20173045

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

2010-01-01

196

Expression of angiotensin II receptor type 1 is reduced in advanced rat liver fibrosis.  

PubMed

In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil (CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced mRNA of profibrotic TGF-beta, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for the prevention of cirrhosis. PMID:17406843

Töx, Ulrich; Scheller, Ingo; Kociok, Norbert; Kern, Michael André; Klanac, Dejan; Daudi, Sharif Mohammed; Laue, Oliver; Schirmacher, Peter; Goeser, Tobias; Schulte, Sigrid; Steffen, Hans Michael

2007-08-01

197

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

PubMed

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

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

2014-11-01

198

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

PubMed

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

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

2014-12-01

199

Myocardial contractility is preserved early but reduced late after ovariectomy in young female rats  

PubMed Central

Background Ovarian sex hormones (OSHs) are implicated in cardiovascular function. It has been shown that OSHs play an important role in the long term regulation of cardiac sarcoplasmic reticulum (SR) function and contractility, although early effects of OSHs deprivation on myocardial contractility have not yet been determined. This study evaluated the early and late effects of OSHs deficiency on left ventricular contractility in rats after ovariectomy. Methods Young female Wistar rats were divided into 3 groups (n = 9-15): sham operated (Sham), ovariectomized (Ovx) and Ovx treated with estradiol (1 mg/kg, i.m., once a week) (Ovx+E2). After 7, 15, 30 and 60 days post Ovx, left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca2+ (0.62 to 3.75 mM) and isoproterenol (Iso 10-8 to 10-2 M) and contractility changes in response to rate changes (0.25 to 3 Hz) were assessed. Protein expression of SR Ca2+-ATPase (SERCA2a) and phospholamban (PLB) in the heart was also examined. Results The positive inotropic response to Ca2+ and Iso at 7, 15, and 30 days after Ovx was preserved. However, at 60 days, the Ovx group had decreased myocardial contractility which was subsequently restored with E2 replacement. The reduction in SERCA2a and increase in PLB expression observed at 60 days after Ovx were restored with E2 replacement. Conclusion This study demonstrated that myocardial contractility and expression of key Ca2+ handling proteins were preserved in the early phase and reduced at long-term during OSHs deprivation. PMID:21513549

2011-01-01

200

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

PubMed Central

The purpose of the present study was to investigate moderate intensity progressive resistance exercise (PRE) in growing adolescent rats and its effect on muscle hypertrophy (defined as an increase in fiber cross-sectional area). We hypothesized that in adolescent animals moderate intensity PRE would increase: 1) fiber cross-sectional area (CSA); 2) myosin heavy chain (MyHC) content; and 3) expression and phosphorylation of cell signaling molecules involved in translational regulation, compared to age-matched sedentary controls (SED). In the PRE group, three-week old male rats were trained to climb a vertical ladder as a mode of PRE training such that by 10 weeks, all animals in the PRE group had progressed to carry an additional 80% of body weight per climb. In agreement with our hypotheses, we observed that 10 weeks of moderate PRE in adolescent animals was sufficient to increase CSA of muscle fibers and increase MyHC content. Average muscle fiber CSA increased by greater than 10% and total MyHC content increased by 35% (p<0.05) in the PRE group compared to SED animals. Concurrently, we investigated sustained changes in the expression and phosphorylation of key signaling molecules that are previously identified regulators of hypertrophy in adult animal models. Contrary to our hypotheses, expression and phosphorylation of the translational regulators mTOR and Akt were not increased in the PRE group. In addition, we observed that the ratio of phosphorylated-to-unphosphorylated ribosomal protein S6 (rpS6) was reduced over six-fold in PRE animals (p<0.05) and total rpS6 protein levels were unchanged between PRE and sedentary animals (p>0.05). We conclude that moderate intensity PRE is sufficient to induce muscle hypertrophy in adolescent animals while the signaling mechanisms associated with muscle hypertrophy may differ between growing adolescents and adults. PMID:22614147

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

2011-01-01

201

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

PubMed

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

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

2012-06-01

202

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

PubMed Central

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

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

2013-01-01

203

Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats.  

PubMed

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

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

2013-01-01

204

Rosuvastatin reduces neointima formation in a rat model of balloon injury  

PubMed Central

Background Processes of restenosis, following arterial injury, are complex involving different cell types producing various cytokines and enzymes. Among those enzymes, smooth muscle cell-derived matrix metalloproteinases (MMPs) are thought to take part in cell migration, degrading of extracellular matrix, and neointima formation. MMP-9, also known as gelatinase B, is expressed immediately after vascular injury and its expression and activity can be inhibited by statins. Using an established in vivo model of vascular injury, we investigated the effect of the HMG-CoA reductase inhibitor rosuvastatin on MMP-9 expression and neointima formation. Materials and methods 14-week old male Sprague Dawley rats underwent balloon injury of the common carotid artery. Half of the animals received rosuvastatin (20 mg/kg body weight/day) via oral gavage, beginning 3 days prior to injury. Gelatinase activity and neointima formation were analyzed 3 days and 14 days after balloon injury, respectively. 14 days after vascular injury, proliferative activity was assessed by staining for Ki67. Results After 14 days, animals in the rosuvastatin group showed a decrease in total neointima formation (0.194 ± 0.01 mm2 versus 0.124 ± 0.02 mm2, p < 0.05) as well as a reduced intima/media ratio (1.26 ± 0.1 versus 0.75 ± 0.09, p < 0.05). Balloon injury resulted in increased activity of MMP-9 3 days after intervention for both rosuvastatin treated animals and controls with no significant difference observed between the groups. There was a trend towards a reduction in the number of Ki67-positive cells 14 days after injury. Conclusions Rosuvastatin attenuates neointima formation without affecting early MMP-9 activity in a rat model of vascular injury. PMID:21159570

2010-01-01

205

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

PubMed Central

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

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

2014-01-01

206

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

PubMed

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

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

2015-02-01

207

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

PubMed Central

Background Soybean is termed a functional food because it contains bioactive compounds. However, its effects are not well known under unbalanced diet conditions. This work is aimed at evaluating the effect of adding whole soy flour to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity markers in rats. Methods In this study, 30 male adult Wistar rats were used, distributed among three groups (n?=?10): AIN-93 M diet, cafeteria diet (CAF) and cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were measured: food intake; weight gain; serum concentrations of triglycerides, total cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS); humidity and lipid fecal content; weight and fat of the liver. The villous height, the crypt depth and the thickness of the duodenal and ileal circular and longitudinal muscle layers of the animals were also measured. Results There was a significant reduction in the food intake in the CAF group. The CAFS showed lower serum concentrations of triglycerides and serum TBARS and a lower percentage of hepatic fat, with a corresponding increase in thickness of the intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c and villous height. The addition of soy did not promote any change in these parameters. Conclusions The inclusion of whole soy flour in a high-fat diet may be helpful in reducing some markers of metabolic risk; however, more studies are required to clarify its effects on unbalanced diets. PMID:24119309

2013-01-01

208

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

PubMed

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

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

2011-02-01

209

Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats  

PubMed Central

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

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

2014-01-01

210

Gestational protein restriction reduces expression of Hsd17b2 in rat placental labyrinth.  

PubMed

Accumulating evidence strongly supports the premise that testosterone may be a key player in fetal programming on hypertension. Studies have shown that gestational protein restriction doubles the plasma testosterone levels in pregnant rats. In this study, we hypothesized that elevated testosterone levels in response to gestational protein restriction were caused by enhanced expression of steroidogenic enzymes or impaired expression of Hsd17b2, a known testosterone inactivator that converts testosterone to androstenedione in placenta. Pregnant Sprague-Dawley rats were fed normal (20% protein, control; n = 10) or a low-protein diet (6% protein, PR; n = 10) from Day 1 of pregnancy until killed at Days 14, 18, or 21. Junctional (JZ) and labyrinth (LZ) zones of placenta were collected for expression assay on steroidogenic genes (Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b2, and Srd5a1) by real-time PCR. The main findings include the following: 1) expressions of Cyp11a1, Hsd3b1, and Cyp17a1 in JZ were not affected by diet but were affected by day of pregnancy; 2) expression of Hsd17b2 in both female and male JZs was remarkably increased by PR at Days 18 and 21 of pregnancy; 3) expressions of Hsd17b2 were reduced by PR in both female and male LZ at Day 18 of pregnancy and in female LZ at Day 21 of pregnancy; and 4) expression of Srd5a1in LZ was not affected by day of pregnancy, gender, or diet. These results indicate that in response to gestational protein restriction, Hsd17b2 may be a key regulator of testosterone levels and associated activities in placental zones, apparently in a paradoxical manner. PMID:22837477

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2012-09-01

211

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

Microsoft Academic Search

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore

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

2011-01-01

212

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

EPA Science Inventory

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

213

Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of  

E-print Network

model of type I diabetes Bora Inceoglua , Karen M. Wagnera , Jun Yanga , Ahmed Bettaiebb , Nils H fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes antidepressants, anticonvulsants, se- rotonin-norepinephrin reuptake inhibitors, opiates, and recently lidocaine

Hammock, Bruce D.

214

Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats Role of Heparin-Binding Domain  

Microsoft Academic Search

Oxidative stress may contribute to hypertension. The goals of this study were to determine whether extracellular superoxide dismutase (ECSOD) reduces arterial pressure in spontaneously hypertensive rats (SHR) and whether its heparin-binding domain (HBD), which is responsible for cellular binding, is necessary for the function of ECSOD. Three days after intravenous injection of an adenoviral vector expressing human ECSOD (AdECSOD), mean

Yi Chu; Shinichiro Iida; Donald D. Lund; Robert M. Weiss; Gerald F. DiBona; Yoshimasa Watanabe; Frank M. Faraci; Donald D. Heistad

215

Induction of hemeoxygenase-1 reduces glomerular injury and apoptosis in diabetic spontaneously hypertensive rats  

PubMed Central

Induction of hemeoxygenase-1 (HO-1) lowers blood pressure and reduces organ damage in hypertensive animal models; however, a potential protective role for HO-1 induction against diabetic-induced glomerular injury remains unclear. We hypothesize that HO-1 induction will protect against diabetes-induced glomerular injury by maintaining glomerular integrity and inhibiting renal apoptosis, inflammation, and oxidative stress. Diabetes was induced with streptozotocin in spontaneously hypertensive rats (SHR) as a model where the coexistence of hypertension and diabetes aggravates the progression of diabetic renal injury. Control and diabetic SHR were randomized to receive vehicle or the HO-1 inducer cobalt protoporphyrin (CoPP). Glomerular albumin permeability was significantly greater in diabetic SHR compared with control, consistent with an increase in apoptosis and decreased glomerular nephrin and ?3?1-integrin protein expression in diabetic SHR. CoPP significantly reduced albumin permeability and apoptosis and restored nephrin and ?3?1-integrin protein expression levels in diabetic SHR. Glomerular injury in diabetic SHR was also associated with increases in NF-?B-induced inflammation and oxidative stress relative to vehicle-treated SHR, and CoPP significantly blunted diabetes-induced increases in glomerular inflammation and oxidative stress in diabetic SHR. These effects were specific to exogenous stimulation of HO-1, since incubation with the HO inhibitor stannous mesoporphyrin alone did not alter glomerular inflammatory markers or oxidative stress yet was able to prevent CoPP-mediated decreases in these parameters. These data suggest that induction of HO-1 reduces diabetic induced-glomerular injury and apoptosis and these effects are associated with decreased NF-?B-induced inflammation and oxidative stress. PMID:22205229

Faulkner, Jessica; Baban, Babak; Saleh, Mohamed A.; Sullivan, Jennifer C.

2012-01-01

216

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

PubMed Central

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

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

2014-01-01

217

Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia–reperfusion damage in the rat  

PubMed Central

Background and purpose: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N ?-nitro-L-arginine methyl ester (L-NAME) in the rat. Experimental approach: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5?mg kg?1day?1 for four weeks, either alone or with L-NAME (35-40?mg kg?1 day?1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1?, thromboxane B2, 8-isoprostane-prostaglandin F2? and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia–reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. Key results: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2? and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. Conclusion and implications: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels. PMID:17245365

Rossoni, G; Manfredi, B; De Gennaro Colonna, V; Berti, M; Guazzi, M; Berti, F

2007-01-01

218

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

PubMed Central

Background This study examined the effects of Palm vitamin E (PVE) and ?-tocopherol (?-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO?+?XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Methods Sixty male Sprague–Dawley rats (200-250?g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or ?-TF at 60?mg/kg body weight. After the treatment period of 28?days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO?+?XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and ?-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and ?-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or ?-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities. PMID:22639913

2012-01-01

219

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

PubMed

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

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

2014-03-01

220

Force deficits after stretches of activated rat muscle-tendon complex with reduced collagen cross-linking  

Microsoft Academic Search

.   The forces produced during stretches of passive and activated muscles, and isometric force deficits after stretching of activated\\u000a muscles were examined in rat plantor flexor muscle-tendon complexes with reduced collagen cross-links (pyridinoline). Female\\u000a Sprague-Dawley rats (n=6, age 87 days) were injected twice daily for 43 days with ?-aminopropionitrile (BAPN, 333 mg\\/kg\\/day i.p.), an inhibitor\\u000a of lysyl oxidase, which is responsible for the

M. E. T. Willems; G. R. Miller; W. T. Stauber

2001-01-01

221

Reduced cocaine-induced serotonin, but not dopamine and noradrenaline, release in rats with a genetic deletion of serotonin transporters.  

PubMed

It has recently been proposed that the increased reinforcing properties of cocaine and ecstasy observed in rats with a genetic deletion of serotonin transporters are the result of a reduction in the psychostimulant-induced release of serotonin. Here we provide the neurochemical evidence in favor of this hypothesis and show that changes in synaptic levels of dopamine or noradrenaline are not very likely to play an important role in the previously reported enhanced psychostimulant intake of these serotonin transporter knockout rats. The results may very well explain why human subjects displaying a reduced expression of serotonin transporters have an increased risk to develop addiction. PMID:25261262

Verheij, Michel M M; Karel, Peter; Cools, Alexander R; Homberg, Judith R

2014-11-01

222

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

PubMed Central

Disturbances of the excitation/inhibition (E/I) balance in the brain were recently suggested as potential factors underlying disorders like autism and schizophrenia resulting in associated behavioral alterations including changes in social and emotional behavior as well as abnormal aggression. Neuronal cell adhesion molecules (nCAMs) and mutations in these genes were found to be strongly implicated in the pathophysiology of these disorders. Neuroligin2 (nlgn2) is a postsynaptic cell adhesion molecule, which is predominantly expressed at inhibitory synapses and required for synapse specification and stabilization. Changes in the expression of nlgn2 were shown to result in alterations of social behavior as well as altered inhibitory synaptic transmission, hence modifying the E/I balance. In our study, we focused on the role of nlgn2 in the dorsal hippocampus in the regulation of emotional and social behaviors. To this purpose, we injected an AAV construct overexpressing nlgn2 in the hippocampus of rats and investigated the effects on behavior and on markers for the E/I ratio. We could show an increase in GAD65, a GABA-synthesizing protein in neuronal terminals, and furthermore, reduced exploration of novel stimuli and less offensive behavior. Our data suggest nlgn2 in the hippocampus to be strongly implicated in maintaining the E/I balance in the brain and thereby modulating social and emotional behavior. PMID:23451101

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

2013-01-01

223

Liquorice plant extract reduces ochratoxin A-induced nephrotoxicity in rats.  

PubMed

To evaluate the protective effect of liquorice plant extract (LPE) on ochratoxin A-induced nephrotoxicity, rats were exposed to ochratoxin A for 28 consecutive days. Biochemical analyses showed that ochratoxin A elevated the serum level of creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransaminase (ALT), and malondialdehyde (MDA) while antioxidant power of the serum was diminished significantly (P<0.05). Histopathological examinations revealed degenerative symptoms in proximal tubules, congestions in renal tissue, and a remarkable infiltration of the inflammatory cells as signs of ochratoxin A nephrotoxicity. Moreover, total antioxidant power of the serum and MDA generation was increased. The test compounds melatonin (MLT) and LPE alleviated most of the biochemical alterations. The results of the histopathological investigations of the kidneys supported these findings confirming the protective effects of the test compounds albeit with some differences in antioxidant potency. Taken together, our data may suggest that LPE like MLT could alleviate an ochratoxin A-reduced antioxidant power of serum and lower the toxin-induced MDA generation. Hence LPE might be considered as a practically antioxidant compound that may be beneficial in the prevention and treatment of ochratoxicosis. PMID:19932604

Malekinejad, H; Farshid, A A; Mirzakhani, N

2011-01-01

224

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

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

225

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

PubMed

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

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

2015-01-01

226

l-Ornithine intake affects sympathetic nerve outflows and reduces body weight and food intake in rats.  

PubMed

Ingesting the amino acid l-ornithine effectively improves lipid metabolism in humans, although it is unknown whether it affects the activities of autonomic nerves that supply the peripheral organs related to lipid metabolism, such as adipose tissues. Thus, we investigated the effects of l-ornithine ingestion on autonomic nerves that innervate adipose tissues and the feeding behaviors of rats. Intragastric injection of l-ornithine (2.5%) in urethane-anesthetized rats activated sympathetic nerve activity to white adipose tissue (WAT-SNA), and stimulated sympathetic nerve activity to brown adipose tissue (BAT-SNA). In addition, WAT-SNA responses to l-ornithine were abolished in rats with ablated abdominal vagal nerves. l-ornithine ingestion for 9 weeks also significantly reduced rats' body weight, food intake, and abdominal fat weight. Proopiomelanocortin (POMC) levels in the hypothalamus and uncoupling protein 1 (UCP1) levels in brown adipose tissue were significantly increased in rats that ingested 2.5% l-ornithine for 9 weeks. These results suggested that ingested l-ornithine was taken up in the gastrointestinal organs and stimulated afferent vagal nerves and activated the central nervous system. Subsequently, increased hypothalamic POMC activated sympathetic neurotransmission to adipose tissues and accelerated energy expenditure. PMID:25526897

Konishi, Yuuki; Koosaka, Yasutaka; Maruyama, Ryuutaro; Imanishi, Kazuki; Kasahara, Kazuaki; Matsuda, Ai; Akiduki, Saori; Hishida, Yukihiro; Kurata, Yasutaka; Shibamoto, Toshishige; Satomi, Jun; Tanida, Mamoru

2015-02-01

227

Dexmedetomidine reduces response tendency, but not accuracy of rats in attention and short-term memory tasks.  

PubMed

The present study investigated the role of alpha 2-adrenergic mechanisms in the performance of motor responses, attention and short-term memory in rats. A low dose (3.0 micrograms/kg, s.c.) of dexmedetomidine, an alpha 2-adrenoceptor agonist, reduced response tendency in an attentional task and a working memory task, but it did not affect the choice accuracy of rats. Atipamezole (300 micrograms/kg), an alpha 2-adrenoceptor antagonist, increased anticipatory responding. Although atipamezole did not affect the number of omissions, it reversed the effects of dexmedetomidine on that parameter. We also investigated the effects of dexmedetomidine in rats with partial destruction of noradrenergic nerves induced by the neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride). On its own, DSP-4 treatment did not affect choice accuracy or behavioural activity of rats in the attentional task. The effects of dexmedetomidine (0.3-3.0 micrograms/kg) on anticipatory responses did not differ between controls and DSP-4 group. Furthermore, the effect on omissions was not consistently diminished in DSP-4 treated rats. These results suggest that the activation of postsynaptic alpha 2-adrenoreceptors may be responsible for dexmedetomidine-induced reduction of response tendency while attention and short-term memory are not markedly affected. PMID:8981606

Ruotsalainen, S; Haapalinna, A; Riekkinen, P J; Sirviö, J

1997-01-01

228

Sildenafil Reduces Inflammation and Prevents Pulmonary Arterial Remodeling of the Monocrotaline - induced Disease in the Wistar Rats  

PubMed Central

ABSTRACT Objectives: Pulmonary arterial hypertension (PAH) is a rare and severe disease with incompletely under stood pathogenesis. PAH is associated with pulmonary arterial remodeling and inflammation. We evaluated the effects of Sildenafil on the Monocrotaline (MCT) –induced disease in Wistar rats, for potential benefit in the early phases of inflammation and vascular remodeling. Material and Methods: MCT-injected rats, MCT-injected sildenafil-treated rats (starting day 1 with 2 x 0.2 mg/day; total of 2 mg/kgc/day) and saline-injected control rats were evaluated at day 14 and day 28 following MCT for pulmonary morphological changes – lesions, inflammation (inflammator y index), arterial morphometry (hypertrophy index), immunohistochemistry for smooth muscle cell marker. Outcomes: The administration of sildenafil following MCT significantly reduced the severity of inflammation in the acute stage of the disease (reduction of the inflammatory index by 6.038% (p <0.05)) and prevented pulmonary arterial remodeling (reduction of the hypertrophy index by 7.306% (p<0.001)). It also improved survival in the early phase with a mortality rate during the first 14 days of 4 in the MCT- exposed rats vs 1 in the MCT-exposed sildenafil-treated rate. Conclusions: Early administration of sildenafil in the MCT experimental PAH improves inflammation and survival, and prevents pulmonary vascular remodeling. Our study suggests that one of the mechanisms involved, besides vasodilatation and anti-proliferative effect, could be a direct anti-inflammatory effect of sildenafil. PMID:23400229

BOGDAN, Stefan; SEFERIAN, Andrei; TOTOESCU, Andreea; DUMITRACHE-RUJINSKI, Stefan; CEAUSU, Mihai; COMAN, Cristin; ARDELEAN, Carmen-Maria; DOROBANTU, Maria; BOGDAN, Miron

2012-01-01

229

Reduced sodium-proton exchange activity in lymphocytes from transgenic rats.  

PubMed

We investigated sodium-proton (Na(+)-H+) exchange activity in transgenic TGR(mRen-2)27 rats, a strain showing fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome, in age-matched normotensive Sprague-Dawley (SD) rats, in spontaneously hypertensive rats (SHR) from the Münster strain, and in normotensive Wistar-Kyoto (WKY) rats. From each strain Na(+)-H+ exchange activity was determined in lymphocytes using the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) by measuring the recovery rate of cytosolic pH (pHi) after intracellular acidification. Resting pHi was not significantly different in transgenic rats (n = 10) compared with SD rats (n = 10) (7.305 +/- 0.038 versus 7.337 +/- 0.031; mean +/- SEM), but resting pHi was significantly lower in lymphocytes from SHR (n = 12) compared with their normotensive WKY counterparts (n = 12) (7.232 +/- 0.030 versus 7.377 +/- 0.022; P < .01). Na(+)-H+ exchange activity was significantly lower in lymphocytes from transgenic rats compared with SD rats (5.102 +/- 0.561 versus 7.385 +/- 0.491 x 10(-3) dpHi/s; P < .01), whereas Na(+)-H+ exchange was significantly enhanced in lymphocytes from SHR compared with WKY rats (5.564 +/- 0.432 versus 3.921 +/- 0.433 x 10(-3) dpHi/s; P < .05). The apparent half-maximal activation of Na(+)-H+ exchange was not significantly different in the strains tested. The present study indicates that hypertension in transgenic rats is not related to Na(+)-H+ exchange overactivity. PMID:8082942

Tepel, M; Klaus, T; Laukemper, S; Zidek, W

1994-09-01

230

Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain  

PubMed Central

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. PMID:21772790

Jang, Dong-Kyu; Park, Sang-In; Han, Young-Min; Jang, Kyung-Sool; Park, Moon-Seo; Chung, Young-An; Kim, Min-Wook; Maeng, Lee-So; Huh, Pil-Woo; Yoo, Do-Sung; Jung, Seong-Whan

2011-01-01

231

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

PubMed Central

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

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

2011-01-01

232

L-745,870 reduces the expression of abnormal involuntary movements in the 6-OHDA-lesioned rat.  

PubMed

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson's disease, but chronic administration is complicated by the development of dyskinesia. We have previously demonstrated that the dopamine D4 receptor antagonist L-745,870 reduces the severity of L-DOPA-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaque without compromising L-DOPA antiparkinsonian benefits. In the current study, we have addressed the effects of L-745,870 on the expression of L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine-lesioned rat. Rats were primed with repeated L-DOPA administration, after which acute challenges of L-DOPA/L-745,870 (vehicle, 0.1, 0.3 and 1?mg/kg) were administered, and AIMs were assessed. Rotarod performance and AIMs were assessed. In L-DOPA-primed rats, L-745,870 (1?mg/kg, but not lower doses) alleviated previously established AIMs (by 84%, P<0.001). Whereas rotarod performance was significantly improved by L-DOPA/vehicle treatment, L-DOPA/L-745,870 failed to improve rotarod performance (P>0.05), suggesting that, in contrast to the MPTP-lesioned macaque, L-745,870 reduces L-DOPA antiparkinsonian benefit in the rat model. Overall, these data suggest that L-745,870 may have a narrow therapeutic window as an antidyskinetic agent in advanced Parkinson's disease. PMID:25303957

Huot, Philippe; Johnston, Tom H; Koprich, James B; Espinosa, Maria C; Reyes, Maria Gabriela; Fox, Susan H; Brotchie, Jonathan M

2015-02-01

233

Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats  

PubMed Central

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP. PMID:24084726

Tie, Ru; Ji, Lele; Nan, Ying; Wang, Wenqing; Liang, Xiangyan; Tian, Fei; Xing, Wenjuan; Zhu, Miaozhang; Li, Rong; Zhang, Haifeng

2013-01-01

234

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

SciTech Connect

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

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

2005-11-01

235

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

NASA Astrophysics Data System (ADS)

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

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

2012-11-01

236

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

PubMed Central

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

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

2011-01-01

237

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

PubMed

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

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

2015-01-15

238

Metformin reduces asymmetric dimethylarginine and prevents hypertension in spontaneously hypertensive rats.  

PubMed

Elevated asymmetric dimethylarginine (ADMA) levels and nitric oxide (NO) deficiency are associated with the development of hypertension. Metformin, an antidiabetic agent, is a structural analog of ADMA. We examined whether metformin can prevent the development of hypertension in spontaneously hypertensive rats (SHRs) by restoration of ADMA-NO balance. SHRs and control normotensive Wistar-Kyoto (WKY) rats were assigned to 4 groups (N = 8 for each group): untreated SHRs and WKY rats, metformin-treated SHRs and WKY rats. Metformin-treated rats received metformin 500 mg/kg per day via oral gavage for 8 weeks. All rats were sacrificed at the age of 12 weeks. We found an increase in the blood pressure of SHRs was prevented by metformin. ADMA levels in the plasma and lung were elevated in SHRs, which metformin prevented. Lung dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme) activity was lower in SHRs than WKY rats. Next, metformin had no effect on protein arginine methyltransferase 1 (ADMA-synthesizing enzyme), DDAH-1, DDAH-2, NO synthase enzymes, and DDAH activity in the kidney. Moreover, metformin increased the levels of NO in kidney. Conclusively, the observed antihypertensive effect of metformin in SHRs is because of the restoration of the ADMA-NO pathway. Our findings support the consideration of metformin as an antihypertensive agent for diabetic patients with prehypertension. PMID:25168015

Tsai, Chih-Min; Kuo, Hsuan-Chang; Hsu, Chien-Ning; Huang, Li-Tung; Tain, You-Lin

2014-12-01

239

Fenugreek seeds reduce aluminum toxicity associated with renal failure in rats  

PubMed Central

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

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

2013-01-01

240

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

PubMed

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

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

2013-12-01

241

Hepatic AQP9 expression in male rats is reduced in response to PPAR? agonist treatment.  

PubMed

The peroxisome proliferator receptor ? (PPAR?) is a key regulator of the hepatic response to fasting with effects on both lipid and carbohydrate metabolism. A role in hepatic glycerol metabolism has also been found; however, the results are somewhat contradictive. Aquaporin 9 (AQP9) is a pore-forming transmembrane protein that facilitates hepatic uptake of glycerol. Its expression is inversely regulated by insulin in male rodents, with increased expression during fasting. Previous results indicate that PPAR? plays a crucial role in the induction of AQP9 mRNA during fasting. In the present study, we use PPAR? agonists to explore the effect of PPAR? activation on hepatic AQP9 expression and on the abundance of enzymes involved in glycerol metabolism using both in vivo and in vitro systems. In male rats with free access to food, treatment with the PPAR? agonist WY 14643 (3 mg·kg(-1)·day(-1)) caused a 50% reduction in hepatic AQP9 abundance with the effect being restricted to AQP9 expressed in periportal hepatocytes. The pharmacological activation of PPAR? had no effect on the abundance of GlyK, whereas it caused an increased expression of hepatic GPD1, GPAT1, and L-FABP protein. In WIF-B9 and HepG2 hepatocytes, both WY 14643 and another PPAR? agonist GW 7647 reduced the abundance of AQP9 protein. In conclusion, pharmacological PPAR? activation results in a marked reduction in the abundance of AQP9 in periportal hepatocytes. Together with the effect on the enzymatic apparatus for glycerol metabolism, our results suggest that PPAR? activation in the fed state directs glycerol into glycerolipid synthesis rather than into de novo synthesis of glucose. PMID:25477377

Lebeck, Janne; Cheema, Muhammad Umar; Skowronski, Mariusz T; Nielsen, Søren; Praetorius, Jeppe

2015-02-01

242

Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application.  

PubMed

Surgical procedures associated with tissue injury are often followed by increased sensitivity to innocuous and noxious stimuli in the vicinity of the surgical wound. The aim of this study was to evaluate the role of transient receptor potential vanilloid 1 receptor (TRPV1) containing nociceptors in this process, by their functional inactivation using a high-concentration intradermal injection of capsaicin in a rat plantar incision model. Paw withdrawal responses to mechanical stimuli (von Frey filaments 10-367mN) and to radiant heat applied on plantar skin were tested in animals treated with capsaicin or the vehicle 6 days and 24h before or 2h after the incision was made. In the vehicle-treated animals, mechanical and thermal sensitivity increased significantly 1-96h following the incision. Capsaicin applied 24h before the surgery was most effective and significantly diminished the development of post-incisional mechanical allodynia and hyperalgesia. Thermal hypoalgesia was present in the incised paw after the capsaicin treatment. Capsaicin application 6 days before the incision induced thermal hypoalgesia before the incision but did not prevent completely the thermal hyperalgesia after the incision, while there was also a reduction of mechanical hypersensitivity. Application of the capsaicin injection after the incision showed its first effect at 2h after the injection and at 24h the effect was comparable with the 6 days pretreatment. Our results show an important role of TRPV1-containing nociceptors in the development of post-surgical hypersensitivity and suggest that local, high-concentration capsaicin treatment could be used to reduce it. PMID:16797124

Pospisilova, Eva; Palecek, Jiri

2006-12-01

243

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

PubMed

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

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

2005-12-01

244

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

PubMed Central

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

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

2014-01-01

245

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

Microsoft Academic Search

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

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

2009-01-01

246

High-Resolution Functional Magnetic Resonance Imaging of the Rat Brain: Mapping Changes in Cerebral Blood Volume Using Iron Oxide Contrast Media  

Microsoft Academic Search

Contrast-enhanced magnetic resonance imaging was used to produce high-resolution activation maps reflecting local changes in cerebral blood volume after a simple sensory stimulus. Activation of the forelimb region of the somatosensory cortex was performed in ?-chloralose-anaesthetized rats with an electrical stimulus (5 V, 3 Hz) delivered through needle electrodes placed subcutaneously on the left forelimb. A gradient echo magnetic resonance

Nicholas van Bruggen; Elmar Busch; James T. Palmer; Simon-Peter Williams; Alexander J. de Crespigny

1998-01-01

247

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

PubMed

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

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

2015-02-01

248

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

Microsoft Academic Search

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

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

2004-01-01

249

Maternal protein restriction reduces expression of angiotensin I-converting enzyme 2 in rat placental labyrinth zone in late pregnancy.  

PubMed

Both the systemic and the uteroplacental renin-angiotensin system (RAS) display dramatic changes during pregnancy. However, whether gestational protein insufficiency affects the expressions of RAS in the placenta remains unknown. In this study, we hypothesized that the expression of Ace2 in the placental labyrinth was reduced by maternal protein restriction. Pregnant Sprague-Dawley rats were fed a normal diet or a low-protein diet (LP) from Day 1 of pregnancy until they were killed at Day 14 or Day 18. The labyrinth zone (LZ) of the placenta was then dissected and snap frozen for expression analysis by quantitative real-time PCR of Ace, Ace2, Agtr1a, Agtr1b, and Agtr2. Formalin-fixed placentas were used for immunohistochemical analysis on ACE and ACE2 proteins. The findings include 1) the expression of Ace2 in rat LZ was reduced by maternal protein restriction in late pregnancy; 2) ACE protein was mainly present in syncytiotrophoblasts, whereas ACE2 protein was found predominantly in fetal mesenchymal tissue and fetal capillaries; 3) Agtr1a was predominant in the rat LZ, and its mRNA levels, but not protein levels, were reduced by LP; 4) expressions of Ace, Ace2, and Agtr1a in the rat LZ and their response to LP occurred in a gender-dependent manner. These results may indicate that a reduced expression of Ace2 and perhaps an associated reduction in angiotensin (1-7) production in the placenta by maternal protein restriction may be responsible for fetal growth restriction and associated programming of adulthood hypertension. PMID:22011389

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2012-02-01

250

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

PubMed

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

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

2001-07-01

251

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

PubMed Central

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

Saha, Shyamali; Prakash, Satya

2014-01-01

252

Ceftriaxone Treatment after Traumatic Brain Injury Restores Expression of the Glutamate Transporter, GLT-1, Reduces Regional Gliosis, and Reduces Post-Traumatic Seizures in the Rat  

PubMed Central

Abstract Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely to post-traumatic epilepsy. Glutamate transport is the only known mechanism of extracellular glutamate clearance, and glutamate transporter 1 (GLT-1) is the major glutamate transporter of the mammalian brain. We tested, by immunoblot, in the rat lateral fluid percussion injury TBI model whether GLT-1 expression is depressed in the cortex after TBI, and whether GLT-1 expression after TBI is restored after treatment with ceftriaxone, a well-tolerated ?-lactam antibiotic previously shown to enhance GLT-1 expression in noninjured animals. We then tested whether treatment with ceftriaxone mitigates the associated regional astrogliosis, as reflected by glial fibrillary acid protein (GFAP) expression, and also whether ceftriaxone treatment mitigates the severity of post-traumatic epilepsy. We found that 7 days after TBI, GLT-1 expression in the ipsilesional cortex was reduced by 29% (n=7/group; p<0.01), relative to the contralesional cortex. However, the loss of GLT-1 expression was reversed by treatment with ceftriaxone (200?mg/kg, daily, intraperitoneally). We found that ceftriaxone treatment also decreased the level of regional GFAP expression by 43% in the lesioned cortex, relative to control treatment with saline (n=7 per group; p<0.05), and, 12 weeks after injury, reduced cumulative post-traumatic seizure duration (n=6 rats in the ceftriaxone treatment group and n=5 rats in the saline control group; p<0.001). We cautiously conclude that our data suggest a potential role for ceftriaxone in treatment of epileptogenic TBI. PMID:23510201

Goodrich, Grant S.; Kabakov, Anatoli Y.; Hameed, Mustafa Q.; Dhamne, Sameer C.; Rosenberg, Paul A.

2013-01-01

253

Forelimb use after focal cerebral ischemia in rats treated with an a2-adrenoceptor antagonist  

E-print Network

in revised form 8 November 2002; accepted 11 November 2002 Abstract Atipamezole, a selective a2-adrenoceptor of the present study was to further characterize the effects of atipamezole treatment combined with enriched. Atipamezole (1.0 mg/kg) or 0.9% NaCl was administered on postoperative days 2 through 11 and 15, 19, and 23

Schallert, Tim

254

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

PubMed

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

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

2014-12-01

255

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

Microsoft Academic Search

It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was\\u000a to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long–Evans rats with\\u000a permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power\\u000a (128 or 10 mW) or no ultrasound

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

256

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

Microsoft Academic Search

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

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

2005-01-01

257

VMH Lesions Reduce Excessive Running Under the Activity–Stress Paradigm in the Rat  

Microsoft Academic Search

We have previously shown that excitation of certain neurons in the ventromedial nucleus of the hypothalamus (VMH) of rats induces hyperrunning activity. The present study investigated the involvement of these VMH neurons in inducing excessive running under the activity–stress paradigm. The VMH of 6-week-old male rats was bilaterally lesioned by administration of kainic acid. Control animals received saline in the

Yumiko Iwamoto; Masugi Nishihara; Michio Takahashi

1999-01-01

258

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

PubMed Central

Rationale Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (gamma tocopherol, ?T) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether ?T supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. Methods F344/N rats were randomized to oral gavage with ?T versus placebo, followed by intranasal LPS (20 ug) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo controlled crossover study where they consumed either a ?T-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 hours after inhaled LPS. The effect of ?T compared to placebo on airway neutrophils post-LPS was compared using a repeated measures analysis of variance. Results In rats, oral ?T supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, ?T treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Conclusion Oral supplementation with ?T reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that ?T is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations. PMID:23402870

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

2013-01-01

259

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

PubMed

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

Janis, Christine M; Figueirido, Borja

2014-12-01

260

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

PubMed

It has been shown that gibbons are able to brachiate with very low mechanical costs. The conversion of muscle activity into smooth, purposeful movement of the limb depends on the morphometry of muscles and their mechanical action on the skeleton. Despite the gibbon's reputation for excellence in brachiation, little information is available regarding either its gross musculoskeletal anatomy or its more detailed muscle-tendon architecture. We provide quantitative anatomical data on the muscle-tendon architecture (muscle mass, physiological cross-sectional area, fascicle length and tendon length) of the forelimb of four gibbon species, collected by detailed dissections of unfixed cadavers. Data are compared between different gibbon species and with similar published data of non-brachiating primates such as macaques, chimpanzees and humans. No quantitative differences are found between the studied gibbon species. Both their forelimb anatomy and muscle dimensions are comparable when normalized to the same body mass. Gibbons have shoulder flexors, extensors, rotator muscles and elbow flexors with a high power or work-generating capacity and their wrist flexors have a high force-generating capacity. Compared with other primates, the elbow flexors of gibbons are particularly powerful, suggesting that these muscles are particularly important for a brachiating lifestyle. Based on this anatomical study, the shoulder flexors, extensors, rotator muscles, elbow flexors and wrist flexors are expected to contribute the most to brachiation. PMID:19519640

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

2009-09-01

261

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

PubMed Central

It has been shown that gibbons are able to brachiate with very low mechanical costs. The conversion of muscle activity into smooth, purposeful movement of the limb depends on the morphometry of muscles and their mechanical action on the skeleton. Despite the gibbon's reputation for excellence in brachiation, little information is available regarding either its gross musculoskeletal anatomy or its more detailed muscle–tendon architecture. We provide quantitative anatomical data on the muscle–tendon architecture (muscle mass, physiological cross-sectional area, fascicle length and tendon length) of the forelimb of four gibbon species, collected by detailed dissections of unfixed cadavers. Data are compared between different gibbon species and with similar published data of non-brachiating primates such as macaques, chimpanzees and humans. No quantitative differences are found between the studied gibbon species. Both their forelimb anatomy and muscle dimensions are comparable when normalized to the same body mass. Gibbons have shoulder flexors, extensors, rotator muscles and elbow flexors with a high power or work-generating capacity and their wrist flexors have a high force-generating capacity. Compared with other primates, the elbow flexors of gibbons are particularly powerful, suggesting that these muscles are particularly important for a brachiating lifestyle. Based on this anatomical study, the shoulder flexors, extensors, rotator muscles, elbow flexors and wrist flexors are expected to contribute the most to brachiation. PMID:19519640

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

2009-01-01

262

Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.  

PubMed

Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. PMID:24656388

Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

2014-05-01

263

[Pharmacokinetic/pharmacodynamic modeling of antipyretic and reducing plasma concentration of NO effects of Rheum palmatum in rat].  

PubMed

Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to characterize the antipyretic and anti-inflammatory effects in rats of Rhein, a major component in rhubarb. Twenty-four healthy male Sprague-Dawley (SD) rats were randomly into four groups, of 6 each. The rats in first group were injected intravenously with lipopolysaccharide (LPS, 100 microg x kg(-1)). The second group rats were given rhubarb decoction (RD, 1.54 g x kg(-1)) by oral administration alone. The rats belonging to third group were administered orally RD 30 min after LPS injection. The rest rats were given normal saline only as control group. Orbital sinus blood sampling was collected at different time points. The Rhein and NO concentration in plasma and body temperature (BT) were measured. Relevant data of PK-PD modeling were performed with Kinetica 5. 0. 11. RD could suppress the rise in BT and plasma NO concentration. The antipyretic and anti-inflammatory responses were best described by a Sigmod-E(max) model. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. The results showed that some parameters such as t1/2, C(max) and AUC were significantly increased in rats treated with LPS, compared to those in rats treated with normal saline. The EC50 for antipyretic effect and decrease of plasma NO concentration was respectively equal to 114.1, 90.80 microg x L(-1). The E(max) for antipyretic effect was about 111% of that for increase in BT after LPS injection. The E(max) for anti-inflammatory action was close to 8.399% of that for elevated NO level after modeling. Meanwhile, there was a difference in pharmacokinetic process of Rhein between the impact of normal saline and LPS. So, it can be concluded that the targets of regulating NO production and BT after RD administration may be at the same location. Not only do that, the antipyretic effect induced by RD maybe completely manifest through reducing the plasma concentration of NO. PMID:23944041

Li, Hong; Zhang, Yan; Yu, Yi-Ping; Wang, Ping; Li, Fan-Fan; Meng, Xian-Li

2013-04-01

264

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats  

PubMed Central

AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ± 0.42 vs 9.76 ± 0.45, P < 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P < 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P < 0.01), ALT (446 ± 91 vs 653 ± 98, P < 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01). CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients. PMID:18680237

Yang, Zhi-Yong; Ling, Yan; Yin, Tao; Tao, Jing; Xiong, Jiong-Xin; Wu, He-Shui; Wang, Chun-You

2008-01-01

265

Diabetes in Old Male Offspring of Rat Dams Fed a Reduced Protein Diet  

PubMed Central

Restricted fetal growth is associated with increased risk for the future development of Type 2 diabetes in humans. The study aim was to assess the glucose tolerance of old (seventeen months) male rats, which were growth restricted in early life due to maternal protein restriction during gestation and lactation. Rat mothers were fed diets containing either 20% or 8% protein and all offspring weaned onto a standard rat diet. In old-age fasting plasma glucose concentrations were significantly higher in the low protein offspring: 8.4 (1.3)mmol/l v. 5.3 (1.3)mmol/l (p = 0.005), Areas under the curves were increased by 67% for glucose (p = 0.01) and 81% for insulin (p = 0.01) in these rats in intravenous glucose tolerance tests, suggesting (a degree of) insulin resistance. These results show that early growth retardation due to maternal protein restriction leads to the development of diabetes in old male rat offspring. The diabetes is predominantly associated with insulin resistance. PMID:12369717

Dorling, Matthew W.; Pawlak, Dorota B.; Ozanne, Susan E.; Hales, C. Nicholas

2001-01-01

266

Recombinant adenoassociated virus 2/5-mediated gene transfer is reduced in the aged rat midbrain.  

PubMed

Clinical trials are examining the efficacy of viral vector-mediated gene delivery for treating Parkinson's disease. Although viral vector strategies have been successful in preclinical studies, to date clinical trials have disappointed. This may be because of the fact that preclinical studies fail to account for aging. Aging is the single greatest risk factor for developing Parkinson's disease and age alters cellular processes utilized by viral vectors. We hypothesized that the aged brain would be relatively resistant to transduction when compared with the young adult. We examined recombinant adeno-associated virus 2/5-mediated green fluorescent protein (rAAV2/5 GFP) expression in the young adult and aged rat nigrostriatal system. GFP overexpression was produced in both age groups. However, following rAAV2/5 GFP injection to the substantia nigra aged rats displayed 40%-60% less GFP protein in the striatum, regardless of rat strain or duration of expression. Furthermore, aged rats exhibited 40% fewer cells expressing GFP and 4-fold less GFP messenger RNA. rAAV2/5-mediated gene transfer is compromised in the aged rat midbrain, with deficiencies in early steps of transduction leading to significantly less messenger RNA and protein expression. PMID:25457558

Polinski, Nicole K; Gombash, Sara E; Manfredsson, Fredric P; Lipton, Jack W; Kemp, Christopher J; Cole-Strauss, Allyson; Kanaan, Nicholas M; Steece-Collier, Kathy; Kuhn, Nathan C; Wohlgenant, Susan L; Sortwell, Caryl E

2015-02-01

267

Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.  

PubMed

Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis. PMID:25514759

Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

2015-01-01

268

VOLUNTARY CONSUMPTION OF ETHYL OLEATE REDUCES FOOD INTAKE AND BODY WEIGHT IN RATS  

PubMed Central

Previous studies have shown that administration of the fatty acids, linoleic and oleic acid, either by intragastric or intraintestinal infusion, suppresses food intake and body weight in rats. While still not fully understood, gut-mediated satiety mechanisms likely are potential effectors of this robust response to gastrointestinal fatty acid infusions. The objective of this study was to assess the effects of voluntary access to an oleic acid derivative, ethyl oleate (EO), on subsequent food intake and body weight in rats. Animals were randomized either to a 12.5% EO diet or a soybean oil diet as a “breakfast,” followed either by two one-hour or one five-hour access periods to standard rodent diet, and food intake and body weights were collected. Across 14 days access, rats consuming EO on both feeding schedules gained less weight and consumed less total kilocalories than rats consuming the SO diet. Further, plasma levels of glucose and insulin were comparable in both EO and SO diet groups. In summary, EO was found to increase weight loss in rats maintained on a 75% food-restriction regimen, and attenuate weight-gain upon resumption of an ad-libitum feeding regimen. These data indicate that voluntary access to EO promoted short-term satiety, compared to SO diet, and that these effects contributed to a important and novel attenuated weight gain in EO-fed animals. PMID:18234242

Kemp, Christopher J.; D’Alessio, David A.; Scott, Robert O.; Kelm, Gary R.; Meller, Stephen T.; Barerra, Jason G.; Seeley, Randy J.; Clegg, Deborah J; Benoit., Stephen C.

2008-01-01

269

Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats.  

PubMed

Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern associated with recreational use of the substituted amphetamine 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic considering that psychiatric disorders such as depression and anxiety and responses to first line treatments for these disorders are associated with 5-HT. In this study the effects of prior exposure to MDMA on behavioural and central neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and antidepressant fluoxetine were examined in rats. Animals were administered MDMA (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine treatment groups received either acute (saline injections for 20 days followed by 3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) drug administration. Prior exposure to MDMA resulted in an attenuation of fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); a behavioural test of antidepressant action. In parallel MDMA treatment resulted in significant regional depletions of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H] paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss was enhanced in animals following chronic fluoxetine administration. Elimination of fluoxetine and its metabolite norfluoxetine from the brain abolished this interaction between MDMA and fluoxetine treatment. Fluoxetine administration reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in animals pre-treated with MDMA. Overall the results show that MDMA induces long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These results have potential clinical relevance, suggesting that 5-HT re-uptake inhibitors such as fluoxetine may be less effective at treating depression in chronic abusers of MDMA. PMID:18824064

Durkin, Sarah; Prendergast, Alison; Harkin, Andrew

2008-12-12

270

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

PubMed

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

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

2014-09-01

271

Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats  

PubMed Central

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

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

2014-01-01

272

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

PubMed

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

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

2015-01-01

273

Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury.  

PubMed

Objective:Spinal cord edema contributes to the pathophysiological mechanisms underlying spinal cord injury (SCI) and is associated with functional recovery after SCI. Early myelotomy may be a promising surgical intervention for reducing SCI-induced edema. However, it remains unclear whether myelotomy can reduce SCI-induced edema. In addition, aquaporin-4 (AQP4) and aquaporin-9 (AQP9) have important roles in the regulation of water homeostasis. Here, we aimed to determine the effects of myelotomy on AQP4 and AQP9 expression and spinal cord edema in a rat model of moderate SCI.Methods:Rats were randomly assigned to three groups: the sham control group (n=22) receiving laminectomy alone; the contusion group (n=44) receiving laminectomy plus contusion; and the myelotomy group (n=44) receiving laminectomy plus contusion followed by myelotomy at 24?h. Functional recovery was estimated by the open-field and inclined plane tests. Spinal cord edema was determined by measuring the water content. The expression of AQP4 and AQP9 was determined by western blot.Results:Compared with the contusion group, myelotomy significantly improved the Basso, Beattie and Bresnahan scores in the open-field test and resulted in a higher mean angle value in the incline plane test. Myelotomy significantly reduced SCI-induced edema at 4 and 6 days after SCI, which was accompanied by downregulation of AQP4 and AQP9 expression.Conclusion:Myelotomy improves locomotor function, reduces edema in rats with SCI and is associated with decreased expression of AQP4 and AQP9.Spinal Cord advance online publication, 2 December 2014; doi:10.1038/sc.2014.209. PMID:25448191

Hu, A-M; Li, J-J; Sun, W; Yang, D-G; Yang, M-L; Du, L-J; Gu, R; Gao, F; Li, J; Chu, H-Y; Zhang, X; Gao, L-J

2014-12-01

274

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

PubMed

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

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

2015-01-01

275

Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalus.  

PubMed

The H-Tx rat has fetal-onset hydrocephalus associated with closure of the cerebral aqueduct and a reduction in the secretory cells of the subcommissural organ (SCO), a circumventricular organ situated in the dorsal wall of the cerebral aqueduct. The objective of this study was to determine the role of the SCO in hydrocephalus pathogenesis. Serial brain sections through aqueduct regions containing the SCO from H-Tx rats, together with non-hydrocephalic Fischer F344 rats, were studied at E16, before hydrocephalus onset, at E17, the beginning of onset, and at P0 when the hydrocephalus was overt. Tissues were immunostained by AFRU, an antibody against the SCO glycoprotein, and for the intermediate filament nestin. The area of SCO cells with AFRU immunostaining and the severity of lateral ventricle dilatation were quantified by image analysis. At E16 all fetuses had distinct SCO ependymal cells, open aqueducts and normal lateral ventricles. The H-Tx fetuses fell into two groups with large areas and small areas of AFRU immunoreactivity, all with a full complement of SCO cells. By E17, fetuses with small areas of immunoreactivity had reduced numbers of tall SCO secretory cells, and most had aqueducts closed posteriorly and dilated ventricles. Three additional fetuses with small areas of immunoreactivity had narrow but patent aqueducts and normal ventricles, and another had an open aqueduct and dilated ventricles. At P0, pups previously identified as hydrocephalic had small areas of AFRU immunoreactivity, an aqueduct that was closed anteriorly but open posteriorly, ventricular dilatation, and an absence of SCO secretory cells. The aqueduct even when closed was lined by typical ependymal cells throughout. Decreased nestin immunostaining accompanied the SCO changes. It is concluded that reduced SCO glycoprotein immunoreactivity precedes both aqueduct closure and expansion of the lateral ventricles in the H-Tx rat. PMID:14722750

Somera, K C; Jones, H C

2004-03-01

276

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

PubMed Central

Background Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain. Methods The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction. Results In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor ? (TNF?), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNF? and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group. Conclusions In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury. PMID:24567814

Kwon, So-Young; Yeom, Jae Hwa

2014-01-01

277

Prevention of high blood pressure by reducing sympathetic innervation in the spontaneously hypertensive rat  

Microsoft Academic Search

It has previously been reported that the increase in blood pressure in the spontaneously hypertensive rat (SHR) occurs concurrently with a marked increase in thickness of the arterial wall and an increase in vascular innervation, particularly for the small muscular arteries. The purpose of the present study was to determine whether prevention of the increase in vascular innervation could prevent

James A. Brock; Dirk F. Van Helden; Peter Dosen; Robert A. Rush

1996-01-01

278

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

EPA Science Inventory

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

279

Inhibition of prostaglandin synthesis reduces the induction of MyoD expression in rat soleus muscle.  

PubMed

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration. PMID:19526318

Monda, M; Vicidomini, C; Viggiano, An; Sampaolo, S; Di Iorio, G; Viggiano, Al; Viggiano, E; De Luca, B

2009-01-01

280

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

Microsoft Academic Search

Background—Intravascular clotting has been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV). We previously identified the expression of tissue factor (TF), the primary cellular initiator of blood coagulation, within the coronary intima, which was associated with neointimal thickening. In the present study, the effect of recombinant hirudin on CAV was assessed in Lewis to Fisher rat heterotopic cardiac allografts.

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

281

Contralateral treatment with lidocaine reduces spinal neuronal activity in mononeuropathic rats  

Microsoft Academic Search

In anaesthetised and paralysed rats with chronic constriction of the sciatic nerve, the effects of subcutaneous contralateral lidocaine (100 ?l) on the activity of lumbar (L4–L5) wide dynamic range neurons ipsilateral to the constriction have been investigated. The results show reduction of the spontaneous hyperactivity for 60 min; suppression or reduction of the responses to contralateral noxious stimulation for 60

Indre Bileviciute-Ljungar; Gabriele Biella; Paola Bellomi; Maria Luisa Sotgiu

2001-01-01

282

Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation.  

PubMed

We recently demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons reduces spinal cord injury (SCI) by inhibiting neutrophil activation through an increase in the endothelial production of prostacyclin (PGI(2)). Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP), reduces ischemia/reperfusion (I/R)-induced tissue injury. However, its precise therapeutic mechanism(s) remains to be elucidated. In the present study, we examined whether ANP reduces I/R-induced spinal cord injury by enhancing sensory neuron activation using rats. ANP increased CGRP release and cellular cAMP levels in dorsal root ganglion neurons isolated from rats in vitro. The increase in CGRP release induced by ANP was reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation, or with (9S, 10S, 12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzodiazocine-10-carboxylic acid hexyl ester (KT5720), an inhibitor of protein kinase A (PKA), suggesting that ANP might increase CGRP release from sensory neurons by activating PKA through an increase in the cellular cAMP level. Spinal cord ischemia was induced in rats using a balloon catheter placed in the aorta. ANP reduced mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. ANP significantly enhanced I/R-induced increases in spinal cord tissue levels of CGRP and 6-keto-prostaglandin F(1alpha). a stable metabolite of PGI(2). ANP inhibited I/R-induced increases in spinal cord tissue levels of tumor necrosis factor and myeloperoxidase. Pretreatment with 4'-chloro-3-methoxycinnamanilide (SB366791), a specific vanilloid receptor-1 antagonist, and indomethacin reversed the effects of ANP. These results strongly suggest that ANP might reduce I/R-induced SCI in rats by inhibiting neutrophil activation through enhancement of sensory neuron activation. PMID:17522345

Nakayama, Takuya; Harada, Naoaki; Asano, Miki; Nomura, Norikazu; Saito, Takayuki; Mishima, Akira; Okajima, Kenji

2007-08-01

283

Withania coagulans Fruit Extract Reduces Oxidative Stress and Inflammation in Kidneys of Streptozotocin-Induced Diabetic Rats  

PubMed Central

The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1?, IL-6, and TNF-?) and immunoregulatory cytokines (IL-4 and IFN-?) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10?mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies. PMID:25295146

Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu

2014-01-01

284

Withania coagulans fruit extract reduces oxidative stress and inflammation in kidneys of streptozotocin-induced diabetic rats.  

PubMed

The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1?, IL-6, and TNF-?) and immunoregulatory cytokines (IL-4 and IFN-?) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10?mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies. PMID:25295146

Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu

2014-01-01

285

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine  

PubMed Central

Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species. PMID:23776614

Borges, Cibele S.; Missassi, Gabriela; Pacini, Enio S. A.; Kiguti, Luiz Ricardo A.; Sanabria, Marciana; Silva, Raquel F.; Banzato, Thais P.; Perobelli, Juliana E.; Pupo, André S.; Kempinas, Wilma G.

2013-01-01

286

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

PubMed Central

The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO3 per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb’s LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 ?m) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb. PMID:21197231

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

2010-01-01

287

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats  

PubMed Central

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

2013-01-01

288

Essential oil of Myrtus communis inhibits inflammation in rats by reducing serum IL-6 and TNF-alpha.  

PubMed

The topical antiinflammatory activity of the essential oil of Myrtus communis L. was studied using croton oil induced ear edema and myeloperoxidase (MPO) activity in mice, and cotton pellet induced granuloma, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats. On topical application, the oil exhibited a significant decrease in the ear edema as well as MPO activity. The oil also inhibited cotton pellet-induced granuloma and serum TNF-alpha and IL-6. It can be concluded that the essential oil of Myrtus communis reduces leukocyte migration to the damaged tissue and exhibits antiinflammatory activity. PMID:22164804

Maxia, Andrea; Frau, Maria Assunta; Falconieri, Danilo; Karchuli, Manvendra Singh; Kasture, Sanjay

2011-10-01

289

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

PubMed

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

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

2011-11-01

290

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys  

PubMed Central

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. PMID:23112841

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

2012-01-01

291

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

Microsoft Academic Search

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

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

1998-01-01

292

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

Microsoft Academic Search

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

T. Hirota; A. Minakawa; M. Muraguchi

1990-01-01

293

Intracerebroventricular Administration of Soy Protein Hydrolysates Reduces Body Weight without Affecting Food Intake in Rats  

Microsoft Academic Search

Some studies suggest that increased consumption of soy protein hydrolysates may cause body weight loss but the mechanism of\\u000a action is unknown. The objective of this investigation was to determine whether intracerebroventricular (i.c.v.) infusion\\u000a of soy protein hydrolysates decrease food intake and body weight. Adult male Sprague Dawley rats (n?=?24) received i.c.v. injections of soy hydrolysate I (SH I) or

Nerissa Vaughn; Anthony Rizzo; Dolores Doane; J. Lee Beverly; Elvira Gonzalez de Mejia

2008-01-01

294

The Phytoestrogen Genistein Reduces Bone Loss in Short-Term Ovariectomized Rats  

Microsoft Academic Search

:   The incidence of fractures and of osteoporosis differs between Oriental and Western Caucasian women. This may depend, at\\u000a least in part, on nutritional factors, including dissimilarities in dietary intake of phytoestrogens. To investigate this\\u000a possibility, 2-month-old female rats were ovariectomized (OVX) or sham-operated (SHAM), fed a casein-based diet, injected\\u000a daily with subcutaneous genistein (GEN), the most abundant and best

P. Fanti; M. C. Monier-Faugere; Z. Geng; J. Schmidt; P. E. Morris; D. Cohen; H. H. Malluche

1998-01-01

295

Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats  

Microsoft Academic Search

Introduction:Excessive gestational body weight gain of mothers may predispose offspring towards obesity and metabolic derangements. It is difficult to discern the effects of maternal obesogenic factors—such as diet and\\/or thrifty genetic predisposition—from gestational weight gain per se.Methods:For this reason, genetically normal Wistar rats that were fed regular chow were rendered hypothalamically obese by chronic third-cerebral ventricular (i3vt) infusion during pregnancy

A. C. M. Heinsbroek; G. van Dijk

2009-01-01

296

Reduced alcohol drinking in adult rats exposed to sucrose during adolescence  

Microsoft Academic Search

Intake of sweet-alcoholic drinks during adolescence is believed to favor alcohol abuse and dependence in adulthood. This study examined the influence of early exposure to ethanol with or without sucrose on the consumption of sweet or alcoholic solutions in adulthood. Adolescent rats (from post-natal day 30–46) were given continuous free access to tap water and either 5% sucrose, 5% ethanol

Leandro F. Vendruscolo; Aliou Badara Gueye; Janaína C. M. Vendruscolo; Kelly J. Clemens; Pierre Mormède; Muriel Darnaudéry; Martine Cador

2010-01-01

297

Low Dietary Calcium Reduces 25-Hydroxycholecalciferol in Plasma of Rats1  

Microsoft Academic Search

We investigated whether dietary factors that are known to increase 1,25-(OH)2-cholecalciferol production can deplete plasma 25-OH-cholecalciferol. Plasma concentration of 25-OH-cholecalciferol, its metabolism in vivo and activities of renal mitochondria! 25-OH-cholecalciferol 1-hydroxylase ( 1-OHase) and 25-OH-cholecalciferol 24-hydroxylase (24-OHase) were measured in rats fed various amounts of calcium (Ca) and phosphorus (P). All diets contained 5 jig (200 lu) cholecalciferol per 100

REINHOLD VIETH

298

Local anesthetics reduce the inhibitory neurotransmitter-induced current in dissociated hippocampal neurons of the rat  

Microsoft Academic Search

The effects of local anesthetics on amino acid-induced currents were examined using the whole-cell configuration of the patch clamp technique in dissociated hippocampal pyramidal neurons of the rat. Lidocaine (3 mM) decreased the glycine-induced Cl? current (Gly-ICl) more potently (to 46% of the control value) than the ?-aminobutyric acid-induced Cl? current (GABA-ICl; to 75%), whereas the agent had little effect

Manami Hara; Yoshihisa Kai; Yoshimi Ikemoto

1995-01-01

299

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats.  

PubMed

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNF?, IL-1?, IL-6, NF?B p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D(3) (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected. PMID:19482377

Cekic, Milos; Cutler, Sarah M; VanLandingham, Jacob W; Stein, Donald G

2011-05-01

300

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats  

PubMed Central

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNF?, IL-1?, IL-6, NF?B p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D3 (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected. PMID:19482377

Cekic, Milos; Cutler, Sarah M.; VanLandingham, Jacob W.; Stein, Donald G.

2013-01-01

301

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

PubMed

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

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

2013-09-01

302

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex  

NASA Astrophysics Data System (ADS)

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

303

Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats  

PubMed Central

Objective Systemic administration of the superoxide scavenger tempol reduces arterial pressure, heart rate and sympathetic nerve activity in normotensive and hypertensive animals. The global nature of the depressor response to tempol suggests an inhibitory influence on cardiovascular pre-sympathetic regions of the brain. This study examined several possible mechanisms for such an effect. Methods and Results In urethane anesthetized rats, as expected, intravenous tempol (120 ?mol/kg) reduced mean arterial pressure, heart rate, and renal sympathetic nerve activity. Concomitant central neuronal recordings revealed reduced spontaneous discharge (spikes/s) of neurons in the paraventricular nucleus (PVN) of hypothalamus (from 2.9 ± 0.4 to 0.8 ± 0.2) and the rostral ventrolateral medulla (RVLM, from 9.8 ± 0.5 to 7.2 ± 0.4), two cardiovascular and autonomic regions of the brain. Baroreceptor-denervated rats had exaggerated sympathetic and cardiovascular responses. Pretreatment with the hydroxyl radical scavenger DMSO (i.v.) attenuated the tempol-induced decreases in blood pressure, heart rate and renal sympathetic nerve activity, but the nitric oxide synthesis inhibitor L-NAME (i.v. or i.c.v.) had no effect. Conclusion These findings suggest that systemically administered tempol acts upon neurons in PVN and RVLM to reduce arterial pressure, heart rate, and renal sympathetic nerve activity, perhaps by reducing the influence of reactive oxygen species in those regions. The arterial baroreflex modulates the depressor responses to tempol. These central mechanisms must be considered in interpreting data from studies using systemically administered tempol to assess the role of reactive oxygen species in cardiovascular regulation. PMID:19330914

Wei, Shun-Guang; Zhang, Zhi-Hua; Yu, Yang; Felder, Robert B.

2010-01-01

304

Decreased activity of folate transporters in lipid rafts resulted in reduced hepatic folate uptake in chronic alcoholism in rats.  

PubMed

Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency, which is due in part to folate malabsorption. The present study deals with the regulatory mechanisms of folate uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20 % solution) orally for 3 months, and the molecular mechanisms of folate uptake were studied in liver. The characterization of the folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of proton coupled folate transporter and folate binding protein in the uptake. The folate transporters were found to be associated with lipid raft microdomain of liver BLM. Moreover, ethanol ingestion decreased the folate transport by altering the Vmax of folate transport process and downregulated the expression of folate transporters in lipid rafts. The decreased transporter levels were associated with reduced protein and mRNA levels of these transporters in liver. The deranged folate uptake together with reduced folate transporter levels in lipid rafts resulted in reduced folate levels in liver and thereby to its reduced levels in serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters. PMID:22956120

Wani, Nissar Ahmad; Nada, Ritambhara; Khanduja, Krishan Lal; Kaur, Jyotdeep

2013-03-01

305

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

PubMed

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

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

2014-06-16

306

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y  

PubMed Central

We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones.Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3?mg?kg?1 day?1 p.o.) or deionized water for 21 days.Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls.The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones. PMID:11309262

Brown, Michael; Bing, Chen; King, Peter; Pickavance, Lucy; Heal, David; Wilding, John

2001-01-01

307

Neither Milk Production, Milk Transfer Nor Pup Growth Hormone Account for Reduced Body Weights of Rat Pups Reared In Hypergravity  

NASA Technical Reports Server (NTRS)

Studies spanning the gravity continuum from 0 to 2-g are revealing new insights into how mammalian reproduction and development may proceed in the microgravity of space. Rat pups reared from either conception or midgestation in hypergravity (hg) weigh 6-15% less than 1-g controls. In the present study we analyzed maternal and pup factors that may account for reduced body weight of hg reared pups. Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g, 1.75-g or 2.0-g. Prolaction (Prl) and oxytocin (OT) were measured in hg-exposed dams during either pregnancy (G20) or lactation (Postnatal day [P] 10). Gravity related differences in Prl were not observed whereas OT was depressed during lactation in hg dams relative to controls (p less than 0.05). Milk transfer measured during a discrete suckling episode was actually increased in hg-reared litters and comparable numbers of milk-letdowns were observed in the two conditions. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on growth hormone (GH) and insulin-like growth factors (IGFs). Plasma GH measured in P10 pups using enzyme immunoassay (EIA) was significantly elevated in hg pups relative to 1-g controls (mean +/- sd., ng/ml: 2.0-g, 10.6 [3.0], 1.5-g 8.9 [4.0], 1.0-g, 7.95 [3.1]). Together, these findings suggest that neither milk production, milk transfer nor pup GH play significant roles in reduced body weights of hg-reared pups. Studies underway are focused on insulin-like growth factors.

Bear, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

2002-01-01

308

Spray-dried porcine plasma reduces the effects of staphylococcal enterotoxin B on glucose transport in rat intestine.  

PubMed

We investigated the intestinal transport of D-glucose (D-Glc) and 3 essential amino acids in a model of intestinal inflammation, and the effects of dietary supplementation with animal plasma proteins on this function. Wistar Lewis rats were fed a diet containing an isonitrogenous amount of milk protein (control group) or a diet supplemented with either spray-dried animal plasma (SDAP) or immunoglobulin concentrate (IC) from porcine plasma, from d 21 of life (weaning) until d 35. On d 30 and 33, rats were challenged intraperitoneally with Staphylococcus aureus enterotoxin B (SEB; groups SEB, SEB-SDAP, and SEB-IC) and on d 35, brush border membrane vesicles (BBMVs) were prepared and used for transport and binding studies. Administration of SEB reduced D-Glc transport across sodium glucose transporter 1 [SGLT1; 20% reduction in maximal transport rate (Vmax); P < 0.05], without affecting the Michaelis constant (Km). The results from specific phlorizin binding, Western blot, and immunohistochemistry supported the view that the effects of SEB are due to reduced expression of D-Glc transporters in the apical membrane. SEB increased the passive diffusion constant (Kd) for D-Glc 3-fold (P < 0.05). SEB did not affect mediated or passive amino acid fluxes of L-leucine, L-methionine, or L-lysine. Dietary SDAP increased the D-Glc Vmax in the SEB group without affecting the passive component. Changes in d-Glc Vmax due to SEB and to the dietary treatments were correlated with changes in the number of SGLT1 transporters present in the BBMVs (r = 0.9468; P < 0.05). Dietary IC had no observed effect. We estimate that, in rats challenged with SEB, SDAP supplementation can increase glucose absorption by 8-9% during the interdigestive periods. PMID:15987845

Garriga, Carles; Pérez-Bosque, Anna; Amat, Concepció; Campbell, Joy M; Russell, Louis; Polo, Javier; Planas, Joana M; Moretó, Miquel

2005-07-01

309

Trx1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in the Infarcted Myocardium of Diabetic Rats  

PubMed Central

Background The present study evaluates the reversal of diabetes mediated impairment of angiogenesis in myocardial infarction (MI) model of Type I diabetic rats by intramyocardial administration of adenoviral vector encoding Thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes mediated impairment of angiogenesis to dysfunctional antioxidant systems in which Trx1 plays a central role. Methods and Results Ad.Trx1 was intramyocardially administered immediately after MI to non-diabetic and diabetic rats. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. The myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1 administered group exhibited reduced fibrosis, oxidative stress and cardiomyocyte and endothelial cell apoptosis as compared to diabetic MI group along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of Trx1, HO-1, VEGF, p38MAPK? and decreased p-JNK and p38MAPK? in the Ad.Trx1 treated diabetic group. Alternatively, we have observed significant reduction in the expression of VEGF in SnPP (HO-1 enzyme inhibitor) treated non-diabetic and diabetic animals even after Ad.Trx1 therapy. Echocardiographic analysis after 4 weeks of MI revealed significant improvement in the myocardial functional parameters such as the ejection fraction, fractional shortening and E/A ratio in the Ad.Trx1 administered group as compared to the diabetic MI group. Conclusion We demonstrate that the infarcted myocardium can be rescued from diabetes related impairment of angiogenesis and reduce myocardial functional disorder by Trx1 gene therapy in streptozotocin induced diabetic rats. PMID:20194885

Samuel, Samson Mathews; Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; Maulik, Gautam; Sudhakaran, Perumana R.; Maulik, Nilanjana

2010-01-01

310

Branched Chain Fatty Acids Reduce the Incidence of Necrotizing Enterocolitis and Alter Gastrointestinal Microbial Ecology in a Neonatal Rat Model  

PubMed Central

Introduction Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model. Methods Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed) ; Control, hand-fed rat milk substitute ; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed. Results NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed. Conclusion At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects. PMID:22194981

Ran-Ressler, Rinat R.; Khailova, Ludmila; Arganbright, Kelly M.; Adkins-Rieck, Camille K.; Jouni, Zeina E.; Koren, Omry; Ley, Ruth E.; Brenna, J. Thomas; Dvorak, Bohuslav

2011-01-01

311

Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats  

PubMed Central

Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-?, IFN-?, IL-1?, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene-modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP. PMID:25120736

Hua, Jie; He, Zhi-Gang; Qian, Dao-Hai; Lin, Sheng-Ping; Gong, Jian; Meng, Hong-Bo; Yang, Ting-Song; Sun, Wei; Xu, Bin; Zhou, Bo; Song, Zhen-Shun

2014-01-01

312

Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.  

PubMed

Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone. PMID:23886859

Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

2013-10-01

313

Salvianolic Acid B Reducing Portal Hypertension Depends on Macrophages in Isolated Portal Perfused Rat Livers with Chronic Hepatitis  

PubMed Central

This study is aimed to investigate the effects of Sal B on portal hypertension (PH). PH with chronic hepatitis was induced by carbon tetrachloride (CCl4) in rats. The model was confirmed with elevated portal pressures and increased serum CD163 levels. The inducible nitric oxide synthase (iNOS) or heme oxygenase-1 (HO-1) in portal triads was assessed. The isolated portal perfused rat liver (IPPRL) was performed at d0, d28, d56 , and d84 in the progression of chronic hepatitis. After constricting with phenylephrine, the portal veins were relaxed with Sal B. The EC50 of Sal B for relaxing portal veins was ?2.04 × 10?9, 7.28 × 10?11, 1.52 × 10?11, and 8.44 × 10?11?mol/L at d0, d28, d56, and d84, respectively. More macrophages infiltrated in portal triads and expressed more iNOS or HO-1 as PH advanced. The areas under the curve (AUCs) of Sal B for reducing PH were positively correlated with the levels of iNOS or HO-1 in portal triads, and so did with serum CD163 levels. Sal B reduces PH in IPPRL with chronic hepatitis, via promoting portal relaxation due to macrophage-originated NO or CO in portal triads, partly at least. PMID:23118797

Zhao, Xin; Jia, Hongmei; Yang, Shijun; Liu, Yuetao; Deng, Bo; Xu, Xueyan; Zhang, Tao; Zhou, Hang; Zu, Chengzhe; Yin, He; Li, Ting; Song, Yijun; Wang, Yueqi; Li, Pengtao; Zou, Zhongmei; Cai, Dayong

2012-01-01

314

Continuous inhibition of poly(ADP-ribose) polymerase does not reduce reperfusion injury in isolated rat heart.  

PubMed

Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 ?M) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis. PMID:23846805

Nishizawa, Kenya; Yanagida, Shigeki; Yamagishi, Tadashi; Takayama, Eiichi; Bessho, Motoaki; Kusuhara, Masatoshi; Adachi, Takeshi; Ohsuzu, Fumitaka

2013-07-01

315

Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension.  

PubMed

This study determined if altered vascular prostacyclin (PGI(2)) and/or thromboxane A(2) (TxA(2)) production with reduced Po(2) contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po(2) under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po(2). Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI(2) production with reduced Po(2) was similar between strains, although TxA(2) production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH(2)/TxA(2) receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA(2), which competes against the vasodilator influences of PGI(2). These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA(2) production and may blunt vascular sensitivity to PGI(2). PMID:18689495

Goodwill, Adam G; James, Milinda E; Frisbee, Jefferson C

2008-10-01

316

Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension  

PubMed Central

This study determined if altered vascular prostacyclin (PGI2) and/or thromboxane A2 (TxA2) production with reduced Po2 contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po2 under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po2. Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI2 production with reduced Po2 was similar between strains, although TxA2 production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH2/TxA2 receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA2, which competes against the vasodilator influences of PGI2. These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA2 production and may blunt vascular sensitivity to PGI2. PMID:18689495

Goodwill, Adam G.; James, Milinda E.; Frisbee, Jefferson C.

2008-01-01

317

Activation of PPAR gamma receptors reduces levodopa-induced dyskinesias in 6-OHDA-lesioned rats.  

PubMed

Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPAR? subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPAR? may represent a new pharmacological target for the treatment of LID. PMID:25486547

Martinez, A A; Morgese, M G; Pisanu, A; Macheda, T; Paquette, M A; Seillier, A; Cassano, T; Carta, A R; Giuffrida, A

2015-02-01

318

Selective Androgen Receptor Modulator (SARM) Treatment Prevents Bone Loss and Reduces Body Fat in Ovariectomized Rats  

Microsoft Academic Search

Purpose  This study was conducted to examine the bone and body composition effects of S-4, an aryl-propionamide derived Selective Androgen\\u000a Receptor Modulator (SARM) in an ovariectomy induced model of accelerated bone loss.\\u000a \\u000a \\u000a \\u000a Methods  One hundred twenty female Sprague–Dawley rats aged to twenty-three weeks were randomly assigned to twelve treatment groups.\\u000a Drug treatment was initiated immediately following ovariectomy and continued for one hundred

Jeffrey D. Kearbey; Wenqing Gao; Ramesh Narayanan; Scott J. Fisher; Di Wu; Duane D. Miller; James T. Dalton

2007-01-01

319

Melatonin Reduces Oxidative Stress and Cardiovascular Changes Induced by Stanozolol in Rats Exposed to Swimming Exercise  

PubMed Central

Objective: Anabolic-androgenic steroids (AAS) are nominated for clinical use to promote protein synthesis in many therapeutic conditions. However, the indiscriminate use of AAS is related to hazardous cardiac disturbances and oxidative stress. We designed a study to investigate whether prolonged treatment with high doses of stanozolol modifies the activities of some antioxidant enzymes in the heart in sedentary and trained rats and whether this treatment causes alterations of cardiovascular parameters. In addition, the effectiveness of melatonin as an antioxidant and as a modulator of the cardiovascular side effects of stanozolol (STA) treatment was analyzed. Materials and Methods: Thirty male Wistar rats were divided into the following six groups: sedentary (S), stanozolol sedentary (SS), stanozolol-melatonin sedentary (SMS), trained (T), stanozolol trained (ST) and stanozolol-melatonin trained (SMT). The stanozolol-treatment rats received 5 mg.kg?1 by subcutaneous injection before each exercise session (5 d.wk?1, i.e., 25 mg.kg?1.wk?1), while control groups received only saline solution injection. The melatonin-treatment groups received intraperitoneal injections of melatonin (10 mg.kg?1), 5 d.wk?1 for 6 wk. Electrocardiography, blood pressure and antioxidant enzyme activity measurements were performed at the end of the experimental period for cardiac function and molecular assessment. Results: This is the first time that the in vivo effects of melatonin treatment on stanozolol-induced cardiovascular side effects have been studied. Stanozolol induced bradycardia and significantly increased cardiac superoxide dismutase and catalase activities. Trained stanozolol-treated rats experienced an increase in blood pressure and relative heart weight, and they developed left cardiac axis deviation. Although melatonin did not prevent cardiac hypertrophy in exercised stanozolol-treated animals, it maintained blood pressure and cardiac catalase activity, and it prevented stanozolol-induced cardiac electrical axis deviation. Conclusion: In conclusion, under our experimental conditions, chronic stanozolol administration induced mild cardiovascular side effects that were partly attenuated by melatonin treatment. However, these results showed that the combination of melatonin and exercise could minimize the stanozolol side effects in the cardiovascular system.

Barbosa dos Santos, Gustavo; Machado Rodrigues, Marcelo José; Gonçalves, Estela Maria; Cintra Gomes Marcondes, Maria Cristina; Areas, Miguel Arcanjo

2013-01-01

320

Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery  

PubMed Central

Abstract We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery. PMID:20873958

Nishibe, Mariko; Barbay, Scott; Guggenmos, David

2010-01-01

321

EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS  

EPA Science Inventory

DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

322

Calcium and ?-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123  

PubMed Central

Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, ?-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or ?-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

2013-01-01

323

Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells.  

PubMed

Brain damage around birth may cause lifelong neurodevelopmental deficits. We examined the therapeutic potential of human umbilical cord blood-derived mononuclear cells containing multipotent stem cells to facilitate motor recovery after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d 7, succeeded by intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells on postnatal d 8 in a sham-controlled design. Histologic and immunohistochemical analysis on postnatal d 21 revealed that neonates developed severe cerebral damage after the hypoxic-ischemic insult. These animals also suffered from contralateral spastic paresis, as evidenced by their locomotor behavior. After transplantation of human umbilical cord blood-derived mononuclear cells, spastic paresis was largely alleviated, resulting in a normal walking behavior. This "therapeutic" effect was accompanied by the fact that mononuclear cells had entered the brain and were incorporated around the lesion without obvious signs of transdifferentiation. This study demonstrates that intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells in a rat model of perinatal brain damage leads to both incorporation of these cells in the lesioned brain area and to an alleviation of the neurologic effects of cerebral palsy as assessed by footprint and walking pattern analysis. PMID:16439586

Meier, Carola; Middelanis, Johannes; Wasielewski, Bianca; Neuhoff, Sandra; Roth-Haerer, Astrid; Gantert, Markus; Dinse, Hubert R; Dermietzel, Rolf; Jensen, Arne

2006-02-01

324

Hesperidin in orange juice reduces the absorption of celiprolol in rats.  

PubMed

It has been reported that the intestinal absorption of celiprolol, an antihypertensive drug, is inhibited when it is taken with orange juice; it has been suggested that element(s) in citrus juice are responsible for this. In the present study, the pharmacokinetic interaction between celiprolol and orange juice was characterized through in vivo experiments with rats. Celiprolol 5 mg/kg was injected into the rat duodenum together with 5 ml/kg of neutralized orange juice or the same concentration of hesperidin as in the orange juice. Plasma celiprolol concentrations were measured by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Concomitant administration of orange juice or hesperidin with celiprolol significantly decreased the area under the plasma concentration-time curve (AUC) by 74% and 75%, respectively, compared with control. These findings suggest that hesperidin is responsible for the decreased absorption of celiprolol and that orange juice taken with celiprolol has an inhibiting effect on intestinal absorption of the drug. PMID:18344215

Uesawa, Yoshihiro; Mohri, Kiminori

2008-04-01

325

Amaranth squalene reduces serum and liver lipid levels in rats fed a cholesterol diet.  

PubMed

In this study, the hypocholesterolaemic effect of amaranth grain, oil and squalene are examined. In experiment 1, rats are given a semi-purified diet containing 1% (w/w) cholesterol for four weeks and either amaranth grain (AG; 300 g/kg) or amaranth oil (AO; 90 g/kg) substituted in experimental groups. Both AG and AO lowered serum and hepatic cholesterol and triglyceride levels. Faecal excretion of cholesterol and bile acid in the AO group increased, while AG affected only bile acid excretion. In experiment 2, rats were fed the cholesterol diet for four weeks and injected (i.p.) with saline (control), amaranth squalene (AS) or shark liver squalene (SS, 200 mg/kg) for seven days. The hypolipidaemic effects of AS were evident in both serum and liver. In addition, AS markedly increased faecal excretions of cholesterol and bile acid, and slightly inhibited 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. In contrast, none of these effects were observed in the SS group. This preliminary study suggests that the cholesterol-lowering effect of AS may be mediated by increased faecal elimination of steroids through interference with cholesterol absorption, and that different sources of squalene (plant versus animal) may affect cholesterol metabolism differently. PMID:15058737

Shin, D H; Heo, H J; Lee, Y J; Kim, H K

2004-01-01

326

Hypocretin Receptor 2 Antagonism Dose-Dependently Reduces Escalated Heroin Self-Administration in Rats.  

PubMed

The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1?h; ShA) or long- (12?h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.Neuropsychopharmacology advance online publication, 3 December 2014; doi:10.1038/npp.2014.293. PMID:25367502

Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

2014-11-01

327

Targeting Müller Cell–Derived VEGF164 to Reduce Intravitreal Neovascularization in the Rat Model of Retinopathy of Prematurity  

PubMed Central

Purpose. To determine whether knockdown of Müller cell–derived VEGFA-splice variant, VEGF164, which is upregulated in the rat retinopathy of prematurity (ROP) model, safely inhibits intravitreal neovascularization (IVNV). Methods. Short hairpin RNAs for VEGF164 (VEGF164.shRNAs) or luciferase.shRNA control were cloned into lentivectors with CD44 promoters that specifically target Müller cells. Knockdown efficiency, off-target effects, and specificity were tested in HEK reporter cell lines that expressed green fluorescent protein (GFP)-tagged VEGF164 or VEGF120 with flow cytometry or in rat Müller cells (rMC-1) by real-time PCR. In the rat oxygen-induced retinopathy (OIR) ROP model, pups received 1 ?L subretinal lentivector-driven luciferase.shRNA, VEGFA.shRNA, or VEGF164.shRNA at postnatal day 8 (P8). Analyses at P18 and P25 included: IVNV and avascular retina (AVA); retinal and serum VEGF (ELISA); density of phosphorylated VEGFR2 (p-VEGFR2) in lectin-labeled retinal endothelial cells (ECs; immunohistochemistry); TUNEL staining and thickness of inner nuclear (INL) and outer nuclear layers (ONL) in retinal cryosections; and pup weight gain. Results. In HEK reporter and in rMC-1 cells and in comparison to lucifferase.shRNA, VEGFA.shRNA reduced both VEGF120 and VEGF164, but VEGF164.shRNA only reduced VEGF164 and not VEGF120. Compared with luciferase.shRNA, VEGFA.shRNA and VEGF164.shRNA reduced retinal VEGF and IVNV without affecting AVA at P18 and P25. At P25, VEGF164.shRNA more effectively maintained IVNV inhibition than VEGFA.shRNA. VEGFA.shRNA and VEGF164.shRNA reduced pVEGFR2 in retinal ECs at P18, but VEGFA.shRNA increased it at P25. VEGFA.shRNA increased TUNEL+ cells at P18 and decreased ONL thickness at P18 and P25. VEGFA.shRNA and VEGF164.shRNA did not affect pup weight gain and serum VEGF. Conclusions. Short hairpin RNA to Müller cell VEGF164 maintained long-term inhibition of IVNV and limited cell death compared with shRNA to VEGFA. PMID:24425851

Jiang, Yanchao; Wang, Haibo; Culp, David; Yang, Zhihong; Fotheringham, Lori; Flannery, John; Hammond, Scott; Kafri, Tal; Hartnett, M. Elizabeth

2014-01-01

328

I.V. infusion of a drag-reducing polymer extracted from aloe vera prolonged survival time in a rat model of acute myocardial ischaemia  

Microsoft Academic Search

Background. I.V. infusion of drag-reducing polymers (DRPs) has been shown to improve survival time in animals subjected to haemorrhagic shock. We hypothesized that DRPs might prolong survival time in rats following acute myocardial ischaemia (AMI). Methods. Sixteen adult male rats were anaesthetized and mechanically ventilated. An i.v. infusion of either Dextran-40 2.5% (Control, n=8) or Dextran-40 2.5% containing 50 m

T. Sakai; B. M. Repko; B. P. Griffith; J. H. Waters; M. V. Kameneva

2006-01-01

329

Integration in descending motor pathways controlling the forelimb in the cat 15. Comparison of the projection from excitatory C3-C4 propriospinal neurones to different species of forelimb motoneurones  

Microsoft Academic Search

In the preceding report (Alstermark and Sasaki 1986) it was shown that a stimulus of 500 µA applied in the lateral reticular nucleus (LRN) evokes a maximal or near monosynaptic EPSP (LRN EPSP) in forelimb motoneurones. This EPSP which is assumed to be selectively mediated by C3-C4 propriospinal neurones (PNs), was used to estimate the strength of the excitatory projection

B. Alstermark; S. Sasaki

1986-01-01

330

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance  

PubMed Central

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 ± 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature. PMID:23604708

Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David

2013-01-01

331

Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus.  

PubMed

Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10? colony-forming units (cfu)/d) and 3040 mg/l (with 10? cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats. PMID:24001238

Lin, Chih-Hsueh; Lin, Cheng-Chieh; Shibu, Marthandam Asokan; Liu, Chiu-Shong; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Hsieh, Cheng-Hong; Chen, Yi-Hsing; Huang, Chih-Yang

2014-02-01

332

Reduced Fecundity in Female Rats with Surgically Induced Endometriosis and in Their Daughters: A Potential Role for Tissue Inhibitors of Metalloproteinase 11  

PubMed Central

The cause of reduced fecundity in women with endometriosis is unknown. Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by both ectopic and eutopic endometrium reportedly has a role in the pathogenesis of endometriosis. We hypothesize that anomalous endometriotic TIMP protein synthesis, secretion, and localization also cause reproductive pathologies resulting in reduced fecundity. An established rat model for endometriosis (Endo) compared with nonendometriotic controls (Shams) was used to investigate reduced fecundity in endometriosis. Comparing Endo and Sham rats, Endo rats had altered ovarian dynamics, including fewer ovarian follicles and corpora lutea with luteinized unruptured follicles. Furthermore, in vivo anomalies in postovulatory oocyte structure and preimplantation embryo development, including misaligned chromosomes, nuclear and cytoplasmic fragmentation, and delayed or arrested cleavage, as well as spontaneous abortions, were found only in Endo rats. A causative role for TIMP1 in these phenomena is supported by our findings that Endo rats have more TIMP1 in their peritoneal fluid as detected by ELISA and more TIMP1 immunolocalization in the theca of antral follicles as measured by computer-assisted morphometric analysis. These data suggest that in endometriosis the accumulation of TIMP1 disrupts the normal MMP/TIMP enzymatic milieu in the peritoneal cavity and negatively affects ovarian dynamics, oocyte quality, and preimplantation embryo development, thereby decreasing fecundity. Most intriguingly, daughters of Endo rats that had no experimental interventions exhibited these same reproductive abnormalities. We predict that developmental exposure to endometriosis leads to permanent epigenetic changes in subsequent generations. PMID:19020297

Stilley, Julie A.W.; Woods-Marshall, Renita; Sutovsky, Miriam; Sutovsky, Peter; Sharpe-Timms, Kathy L.

2008-01-01

333

Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats  

PubMed Central

Background Diets producing a high glycemic response result in exaggerated insulin secretion which induces hepatic lipogenesis, contributing to development of insulin resistance and fatty liver. Viscous dietary fibers blunt the postprandial rise in blood glucose, however their effect on type 2 diabetes and obesity are not entirely known. This study examined the effect of chronic consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids in an obese diabetic rat model. Methods Three groups of Zucker Diabetic Fatty (ZDF) rats were fed diets containing either 5% non-viscous cellulose (control), low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HV- HPMC) for six weeks. Zucker lean littermates consuming cellulose served as a negative control. Markers of glucose control, including oral glucose tolerance test, glycated hemoglobin and urinary glucose, were measured as well as adiposity and the accumulation of liver lipids. Results The HPMC diets increased the viscosity of the small intestinal contents and reduced the postprandial rise in blood glucose. The food efficiency ratio was greater with HPMC feeding compared to the obese control and urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups had lower glycated hemoglobin and kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC group compared to the obese control group. The HV-HPMC group also had lower concentrations of liver lipid and cholesterol and reduced liver weight. However, HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle concentration of acylcarnitines, a lipid intermediate in fatty acid ?-oxidation, was not different between the HPMC groups and obese control, suggesting no change in muscle fatty acid oxidation by HPMC. Conclusions Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting, improved glucose control and reduced insulin resistance and fatty liver in a model of obesity with diabetes. PMID:23146593

2012-01-01

334

Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase.  

PubMed

Etoposide is a chemotherapeutic agent that induces cell death by blocking topoisomerase II catalytic function. Although etoposide is effective in the treatment of cancer, it also causes the death of normal proliferating cells, including male germ cells. Administration of etoposide during the prepubertal phase causes diturbances in several testicular morphometric parameters and in Sertoli cells. Cytoprotection of the seminiferous epithelium is the only means of preserving potential male reproduction in prepubertal cancer patients. Carnitine, an amino acid naturally present in normal cells, is a promising cryoprotectant as it is concentrated in the epididymis and promotes sperm maturation. We have therefore investigated whether carnitine protects rat testes against etoposide and, thus, improves fertility in adulthood. Our results suggest that carnitine partially protects the testis against damage caused by etoposide, although the mechanism by which it happens remains unknown. PMID:19444474

Okada, Fatima Kazue; Stumpp, Taiza; Miraglia, Sandra Maria

2009-08-01

335

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats  

PubMed Central

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis. PMID:24519128

Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

2014-01-01

336

Petroselinic acid from dietary triacylglycerols reduces the concentration of arachidonic acid in tissue lipids of rats.  

PubMed

Studies in vitro have revealed that triacylglycerols containing petroselinoyl [18:1(n-12)] moieties are hydrolyzed by pancreatic lipase at much lower rates than other triacylglycerols. To assess the lipolysis and absorption in vivo of such unusual triacylglycerols, diets containing 120 g seed oil triacylglycerols of coriander (Coriandrum sativum) per kg diet at a level of 72 g 18:1(n-12) moieties/100 g oil were fed to a group of weaned male Wistar rats without restriction for a period of 10 wk. For comparison, groups of rats were fed similar isocaloric diets containing plant oil triacylglycerols with various levels of oleoyl [18:1(n-9)] moieties, e.g., high oleic sunflower seed oil [75 g 18:1(n-9)/100 g oil], olive oil [(66 g 18:1(n-9)/100 g oil], medium oleic rapeseed oil [54 g 18:1(n-9)/100 g oil] and conventional high linoleic sunflower seed oil [25 g 18:1(n-9)/100 g oil]. All diets were supplemented with 20 g corn oil/kg diet. Consumption of coriander oil, compared with the other oils, led to significantly greater liver weights. No significant differences were observed among the groups fed various levels of oleic acid in body weight, the weights of heart, liver, kidneys, spleen or testes, lipid content of heart, or total cholesterol, HDL cholesterol and triacylglycerol concentrations of blood plasma. Ingestion of coriander oil led to incorporation of 18:1(n-12) into heart, liver and blood lipids and to a significant reduction in the concentration of arachidonic acid in the lipids of heart, liver and blood with a concomitant increase in the concentration of linoleic acid compared with results for the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7782911

Weber, N; Richter, K D; Schulte, E; Mukherjee, K D

1995-06-01

337

Grape seed procyanidin extract reduces the endotoxic effects induced by lipopolysaccharide in rats.  

PubMed

Acute inflammation is a response to injury, infection, tissue damage, or shock. Bacterial lipopolysaccharide (LPS) is an endotoxin implicated in triggering sepsis and septic shock, and LPS promotes the inflammatory response, resulting in the secretion of proinflammatory and anti-inflammatory cytokines such as the interleukins (IL-6, IL-1?, and IL-10) and tumor necrosis factor-? by the immune cells. Furthermore, nitric oxide and reactive oxygen species levels increase rapidly, which is partially due to the activation of inducible nitric oxide synthase in several tissues in response to inflammatory stimuli. Previous studies have shown that procyanidins, polyphenols present in foods such as apples, grapes, cocoa, and berries, have several beneficial properties against inflammation and oxidative stress using several in vitro and in vivo models. In this study, the anti-inflammatory and antioxidant effects of two physiological doses and two pharmaceutical doses of grape seed procyanidin extract (GSPE) were analyzed using a rat model of septic shock by the intraperitoneal injection of LPS derived from Escherichia coli. The high nutritional (75mg/kg/day) and the high pharmacological doses (200mg/kg/day) of GSPE showed anti-inflammatory effects by decreasing the proinflammatory marker NOx in the plasma, red blood cells, spleen, and liver. Moreover, the high pharmacological dose also downregulated the genes Il-6 and iNos; and the high nutritional dose decreased the glutathione ratio (GSSG/total glutathione), further illustrating the antioxidant capability of GSPE. In conclusion, several doses of GSPE can alleviate acute inflammation triggered by LPS in rats at the systemic and local levels when administered for as few as 15 days before the injection of endotoxin. PMID:23439188

Pallarès, Victor; Fernández-Iglesias, Anabel; Cedó, Lídia; Castell-Auví, Anna; Pinent, Montserrat; Ardévol, Anna; Salvadó, Maria Josepa; Garcia-Vallvé, Santiago; Blay, Mayte

2013-07-01

338

High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague-Dawley rats.  

PubMed

Central application of apelin elevates blood pressure and influences neuroendocrine responses to stress and food consumption. However, it is not known whether the central cardiovascular effects of apelin depend also on caloric intake or chronic stress. The purpose of the present study was to determine the effects of intracerebroventricular administration of apelin on blood pressure (mean arterial blood pressure) and heart rate in conscious Sprague-Dawley rats consuming either a normal-fat diet (NFD) or high-fat diet (HFD) for 12 weeks. During the last 4 weeks of the food regime, the rats were exposed (NFDS and HFDS groups) or not exposed (NFDNS and HFDNS groups) to chronic stress. Each group was divided into two subgroups receiving intracerebroventricular infusions of either vehicle or apelin. Apelin elicited significant increase of mean arterial blood pressure and heart rate in the NFDNS rats. This effect was abolished in the HFDNS, HFDS and NFDS groups. HFD resulted in a significant elevation of blood concentrations of total cholesterol, triglycerides glucose and insulin. Chronic stress reduced plasma concentration of total and high-density lipoprotein cholesterol, and increased plasma corticosterone concentration and APJ receptor mRNA expression in the hypothalamus, whereas a combination of a HFD with chronic stress resulted in the elevation of plasma triglycerides, total cholesterol and low-density lipoprotein cholesterol, and in increased plasma corticosterone concentration, apelin concentration and APJ receptor mRNA expression in the hypothalamus. It is concluded that a HFD and chronic stress result in significant suppression of the central pressor action of apelin, and cause significant though not unidirectional changes of metabolic and endocrine parameters. PMID:25311903

Cudnoch-Jedrzejewska, Agnieszka; Gomolka, Ryszard; Szczepanska-Sadowska, Ewa; Czarzasta, Katarzyna; Wrzesien, Robert; Koperski, Lukasz; Puchalska, Liana; Wsol, Agnieszka

2015-01-01

339

A comparative study of the arterial supply to the distal sesamoid bones of the equine forelimb and hindlimb / by Philip Tracy James  

E-print Network

A COMPARATIVE STUDY OF THE ARTERIAL SUPPLY TO THE DISTAL SESAMOID BONES OF THE EQUINE FORELIMB AND HINDLIMB A Thesis by PHILIP TRACY JAMES Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement... for the degree of MASTER OF SCIENCE December 1979 Major Subject: Veterinary Anatomy A COMPARATIVE STUDY OF THE ARTERIAL SUPPLY TO THE DISTAL SESAMOID BONES OF THE EQUINE FORELIMB AND HINDLIMB A Thesis by PHILIP TRACY JAMES Approved as to style...

James, Philip Tracy

2012-06-07

340

Raldh expression in embryos of the direct developing frog Eleutherodactylus coqui and the conserved retinoic acid requirement for forelimb initiation.  

PubMed

Embryos of the direct developing frog, Eleutherodactylus coqui, provide opportunities to examine frog early limb development that are not available in species with tadpoles. We cloned two retinaldehyde dehydrogenase genes, EcRaldh1 and EcRaldh2, to see which enzyme likely supplies retinoic acid for limb development. EcRaldh1 is expressed in the dorsal retina, otic vesicle, pronephros, and pronephric duct, but not in the limb. EcRaldh2 is expressed early at the blastoporal lip and then in the mesoderm in the neurula, so this expression could function in forelimb initiation. Later EcRaldh2 is expressed in the mesoderm at the base of the limbs and in the ventral spinal cord where motor neurons innervating the limbs emerge. These observations on a frog support the functional conservation of EcRaldh2 in forelimb initiation in Osteichthyans and in limb patterning and motor neuron specification in tetrapods. PMID:18668545

Elinson, Richard P; Walton, Zachary; Nath, Kimberly

2008-11-15

341

Rapeseed oil fortified with micronutrients reduces atherosclerosis risk factors in rats fed a high-fat diet  

PubMed Central

Background Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to cardiovascular system, but most of these micronutrients are removed by the refining process. The aim of this study was to determine the effect of rapeseed oil fortified with these micronutrients on the atherosclerosis risk factors in rats fed a high-fat diet. Methods The rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified refined rapeseed oil with low, middle and high quantities of these micronutrients (L-, M- and H-FRRO). Forty male SD rats were divided into four groups. One group received RRO diet and other groups received L-, M- and H-FRRO diet for 10 weeks. Results Micronutrients supplementation significantly increased plasma antioxidant defense capacities, as evaluated by the significant elevation in the activities of GPx, CAT and SOD as well as the level of GSH, and the significant decline in lipid peroxidation. These micronutrients also reduced the plasma contents of TG, TC and LDL-C and increased the ratio of HDL-C/LDL-C. In addition, in parallel with the enhancement of these micronutrients, plasma levels of IL-6 and CRP declined remarkably. Conclusion Rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent atherogenesis by ameliorating plasma oxidative stress, lipid profile and inflammation. PMID:21663699

2011-01-01

342

Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain  

PubMed Central

Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

2011-01-01

343

Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.  

PubMed

Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

2011-11-01

344

Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats  

PubMed Central

Among rodents that carry hantaviruses, males are more likely to engage in aggression and to be infected than females. One mode of hantavirus transmission is via the passage of virus in saliva during wounding. The extent to which hantaviruses cause physiological changes in their rodent host that increase aggression and, therefore, virus transmission has not been fully documented. To assess whether steroid hormones and neurotransmitters contribute to the correlation between aggression and Seoul virus infection, Norway rats were trapped in Baltimore, Maryland and wounding, infection status, steroid hormones, and concentrations of neurotransmitters, including norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenol acetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) in select brain regions were examined. Older males and males with high-grade wounds were more likely to have anti-Seoul virus IgG and viral RNA in organs than either juveniles or adult males with less severe wounds. Wounded males had higher circulating testosterone, lower hypothalamic 5-HIAA, and lower NE in the amygdala than males with no wounds. Infected males had higher concentrations of testosterone, corticosterone, NE in the hypothalamus, and DOPAC in the amygdala than uninfected males, regardless of wounding status. In the present study, wounded males that were infected with Seoul virus had elevated testosterone and reduced 5-HIAA concentrations, suggesting that these neuroendocrine mechanisms may contribute to aggression and the likelihood of transmission of hantavirus in natural populations of male Norway rats. PMID:17719050

Easterbrook, Judith D.; Kaplan, Jenifer B.; Glass, Gregory E.; Pletnikov, Mikhail V.; Klein, Sabra L.

2007-01-01

345

Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia  

PubMed Central

Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia. PMID:23109432

Ibebunjo, Chikwendu; Chick, Joel M.; Kendall, Tracee; Eash, John K.; Li, Christine; Zhang, Yunyu; Vickers, Chad; Wu, Zhidan; Clarke, Brian A.; Shi, Jun; Cruz, Joseph; Fournier, Brigitte; Brachat, Sophie; Gutzwiller, Sabine; Ma, QiCheng; Markovits, Judit; Broome, Michelle; Steinkrauss, Michelle; Skuba, Elizabeth; Galarneau, Jean-Rene; Gygi, Steven P.

2013-01-01

346

Unilateral injection of A?25-35 in the hippocampus reduces the number of dendritic spines in hyperglycemic rats.  

PubMed

Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several risk factors including impaired glucose metabolism in the brain that could cause molecular and neurochemical alterations in cognitive regions such as the hippocampus (Hp). Consequently, this process could cause neuronal morphological changes; however, the mechanism remains elusive. We induced chronic hyperglycemia after streptozotocin (STZ) administration. Then, we examined spatial learning and memory using the Morris water maze test and evaluated neuronal morphological changes using the Golgi-Cox stain procedure in hyperglycemic rats that received a A?25-35 unilateral injection into the Hp. Our results demonstrate that STZ combined with A?25-35 induced significant deficits in the spatial memory. In addition, we observed a significant reduction in the number of dendritic spines of pyramidal neurons in the dorsal Hp of rats with STZ plus A?25-35 . In conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp could produce the spatial memory deficit observed in these animals. These results suggest that hyperglycemia can trigger A?-induced neurodegeneration and thus the appearance of AD symptoms would be accelerated. Synapse, 2014. © 2014 Wiley Periodicals, Inc. PMID:25049192

Lazcano, Zayda; Solis, Oscar; Bringas, María Elena; Limón, Daniel; Diaz, Alfonso; Espinosa, Blanca; García-Peláez, Isabel; Flores, Gonzalo; Guevara, Jorge

2014-07-22

347

Improved efficacy and reduced toxicity by ultrasound-guided intrahepatic injections of helper-dependent adenoviral vector in Gunn rats.  

PubMed

Crigler-Najjar syndrome type I is caused by mutations of the uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) gene resulting in life-threatening increase of serum bilirubin. Life-long correction of hyperbilirubinemia was previously shown with intravenous injection of high doses of a helper-dependent adenoviral (HDAd) vector expressing UGT1A1 in the Gunn rat, the animal model of Crigler-Najjar syndrome. However, such high vector doses can activate an acute and potentially lethal inflammatory response with elevated serum interleukin-6 (IL-6). To overcome this obstacle, we investigated safety and efficacy of direct injections of low HDAd doses delivered directly into the liver parenchyma of Gunn rats. Direct hepatic injections performed by either laparotomy or ultrasound-guided percutaneous injections were compared with the same doses given by intravenous injections. A greater reduction of hyperbilirubinemia and increased conjugated bilirubin in bile were achieved with 1 × 10(11) vp/kg by direct liver injections compared with intravenous injections. In sharp contrast to intravenous injections, direct hepatic injections neither raised serum IL-6 nor resulted in thrombocytopenia. In conclusion, ultrasound-guided percutaneous injection of HDAd vectors into liver parenchyma resulted in improved hepatocyte transduction and reduced toxicity compared with systemic injections and is clinically attractive for liver-directed gene therapy of Crigler-Najjar syndrome. PMID:23947957

Pastore, Nunzia; Nusco, Edoardo; Piccolo, Pasquale; Castaldo, Sigismondo; Vaníkova, Jana; Vetrini, Francesco; Palmer, Donna J; Vitek, Libor; Ng, Philip; Brunetti-Pierri, Nicola

2013-10-01

348

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.  

PubMed

Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

Erdely, Aaron; Antonini, James M; Young, Shih-Houng; Kashon, Michael L; Gu, Ja K; Hulderman, Tracy; Salmen, Rebecca; Meighan, Terence; Roberts, Jenny R; Zeidler-Erdely, Patti C

2014-01-01

349

The effect of gait and digital flexor muscle activation on limb compliance in the forelimb of the horse Equus caballus  

Microsoft Academic Search

A horse's legs are compressed during the stance phase, storing and then returning elastic strain energy in spring- like muscle-tendon units. The arrangement of the muscle- tendon units around the lever-like joints means that as the leg shortens the muscle-tendon units are stretched. The forelimb anatomy means that the leg can be conceptually divided into two springs: the proximal spring,

M. Polly McGuigan; Alan M. Wilson

2003-01-01

350

The development of femoral osteopenia in ovariectomized rats is not reduced by high intensity treadmill training: a mechanical and densitometric study.  

PubMed

The effect of treadmill running on the development of osteopenia was investigated in adult ovariectomized (OVX) rats compared with sedentary OVX and sedentary sham-operated rats. The rats were 3 months old with a mean weight of 214 g. OVX rats were fed a low calcium diet (0.01%), and the sham rats received the normal diet (1.1% calcium). The training consisted of treadmill running at a speed of 27 m/minute for 1 hour 5 out of 7 days during a period of 8 1/2 weeks. The weight gain was higher in the sedentary OVX (108 g) than in the training OVX (62 g) and sham-operated rats (61 g) (P < 0.001). Comparing the two OVX groups, training had no significant effects on the development of femoral osteopenia as assessed by mechanical testing of the femoral shaft and neck, and by bone mass measurements by dual energy X-ray absorptiometry (DXA) or by ashing. Comparing all three groups bone mineral content (BMC) and bone mineral density (BMD) were reduced by more than 40% in both the OVX groups compared with the sham-operated rats (P < 0.001). Ash weight and calcium content were reduced by approximately 40% in both OVX groups. Femoral volume and length were 10% higher in the sedentary OVX animals compared with the trained (P < 0.05), indicating that the training had had a negative effect on the growth changes induced by ovariectomy. The fracture strength of the femoral shaft was reduced by 26% and 22% in the trained and sedentary OVX rats, respectively compared with the sham-operated group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7895182

Nordsletten, L; Kaastad, T S; Madsen, J E; Reikerås, O; Ovstebø, R; Strømme, J H; Falch, J

1994-12-01

351

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats  

PubMed Central

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (?9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

352

Motor Skills Training Enhances Lesion-Induced Structural Plasticity in the Motor Cortex of Adult Rats  

Microsoft Academic Search

To assess behavioral experience effects on synaptic plasticity after brain damage, the present study examined the effects of complex motor skills training (the acrobatic task) on synaptic changes in layer V of the motor cortex opposite unilateral damage to the forelimb sensorimotor cortex (FLsmc). Adult male rats were given lesions or sham operations followed by 28 d of training on

Theresa A. Jones; Catherine J. Chu; Lucinda A. Grande; Aurora D. Gregory

1999-01-01

353

A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats  

Microsoft Academic Search

In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague–Dawley rats for 2h. Either CM

Juhui Zhao; Jinhai Wang; Lei Dong; Hongyang Shi; Zongyan Wang; Hui Ding; Haitao Shi; Xiaolan Lu

2011-01-01

354

Decreased cardiac excitability secondary to reduction of sodium current may be a significant contributor to reduced contractility in a rat model of sepsis  

PubMed Central

Introduction Multisystem organ failure remains a poorly understood complication of sepsis. During sepsis, reduced excitability contributes to organ failure of skeletal muscle, nerves and the spinal cord. The goal of this study was to determine whether reduced excitability might also contribute to cardiac failure during sepsis. Methods Wistar rats were made septic by cecal ligation and puncture. One day later, action potentials were recorded from beating left ventricular papillary muscle ex vivo by impaling myocytes with sharp microelectrodes. Results In cardiac papillary muscle from septic rats, action potential amplitude and rate of rise were reduced, while threshold was elevated. These changes in action potential properties suggest sepsis selectively reduces sodium current. To determine the effects of selective reduction in sodium current, we applied tetrodotoxin to papillary muscle from healthy rats and found reduction in action potential amplitude and rate of rise, as well as elevation of threshold. The changes were similar to those triggered by sepsis. Blocking calcium current using nifedipine did not mimic action potential changes induced by sepsis. Contractility of healthy papillary muscle was reduced to 40% of normal following partial block of sodium current by tetrodotoxin, close to the low contractility of septic papillary muscle, which was 30% of normal. Conclusions Our data suggest cardiac excitability is reduced during sepsis in rats. The reduction in excitability appears to be primarily due to reduction of sodium current. The reduction in sodium current may be sufficient to explain most of the reduction in cardiac contractility during sepsis. PMID:24669759

2014-01-01

355

Inferring the use of forelimb suspensory locomotion by extinct primate species via shape exploration of the ulna.  

PubMed

Uncovering links between skeletal morphology and locomotor behavior is an essential component of paleobiology because it allows researchers to infer the locomotor repertoire of extinct species based on preserved fossils. In this study, we explored ulnar shape in anthropoid primates using 3D geometric morphometrics to discover novel aspects of shape variation that correspond to observed differences in the relative amount of forelimb suspensory locomotion performed by species. The ultimate goal of this research was to construct an accurate predictive model that can be applied to infer the significance of these behaviors. We studied ulnar shape variation in extant species using principal component analysis. Species mainly clustered into phylogenetic groups along the first two principal components. Upon closer examination, the results showed that the position of species within each major clade corresponded closely with the proportion of forelimb suspensory locomotion that they have been observed to perform in nature. We used principal component regression to construct a predictive model for the proportion of these behaviors that would be expected to occur in the locomotor repertoire of anthropoid primates. We then applied this regression analysis to Pliopithecus vindobonensis, a stem catarrhine from the Miocene of central Europe, and found strong evidence that this species was adapted to perform a proportion of forelimb suspensory locomotion similar to that observed in the extant woolly monkey, Lagothrix lagothricha. PMID:25234204

Rein, Thomas R; Harvati, Katerina; Harrison, Terry

2015-01-01

356

Combination of carvacrol with methotrexate suppresses Complete Freund's Adjuvant induced synovial inflammation with reduced hepatotoxicity in rats.  

PubMed

The present study evaluated the therapeutic benefit of the combination of carvacrol, an isoprenoid having potential anti-inflammatory action, with methotrexate in suppressing Complete Freund's Adjuvant induced arthritis and attenuating methotrexate induced hepatic damage. Arthritis was induced in rats with Complete Freund's Adjuvant. Animals received methotrexate (2mg/kg) intraperitonealy once a week for 5 weeks alone and along with carvacrol orally (50 and 100mg/kg) respectively from the 10th to the 42nd day. Control and carvacrol alone group were also studied. Paw volume, hypernociception, and erythrocyte sedimentation rate were evaluated as arthritic markers. Hepatic marker enzymes in serum; myeloperoxidase, protein oxidation, and oxidative measures were determined in the liver homogenate. Liver histological assessments were also carried out. Methotrexate significantly controlled arthritis; however, liver damage was evident due to oxidative stress and rise in myeloperoxidase levels. Carvacrol suppressed the hyperalgesic response, significantly alleviated arthritis and reduced damage to the hepatocytes owing to a decline in the levels of myeloperoxidase and oxidative markers. High dose of the combination reduced the levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase by 24.74%, 30.2% and 28.14% compared with methotrexate treatment. Histological assessment also revealed that carvacrol minimizes methotrexate induced liver toxicity. In combination, carvacrol promoted the anti-arthritic action of methotrexate, reduced neutrophils infiltration and peroxidative damage to the liver. Therefore, carvacrol can serve as a useful adjuvant and promote the safe use of methotrexate in the management of arthritis. PMID:24333217

Banji, Otilia J F; Banji, David; Soumya, N; Chilipi, Kiran Kumar; Kalpana, C H; Kranthi Kumar, C H; Annamalai, A R

2014-01-15

357

Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability.  

PubMed

Calorie restriction and the ketogenic diet have been successfully used in models of neuroprotection. However, there are limitations in clinical application of these diets and attention has turned to understanding their mechanism of action. Ketone bodies are produced in both diets and maybe involved in their ability to attenuate neuronal injury. This study seeks to assess the effects of ketone bodies on neuronal transmission and their efficacy in reducing the impact of known excitotoxins. We made use of extracellular recordings from rat hippocampal slices and demonstrate that ketone bodies had no effect on neuronal transmission or induction of long-term potentiation (LTP). Perfusion of slices with N-methyl-d-aspartate (NMDA, 15 ?M) produced neuronal depression suggestive of cell injury (antidromic recording also demonstrated similar depression), such that recovery of population spike potentials after 60 minutes was 27% in normal (10 mM) glucose but only 7% during reduced (2·5 mM) glucose availability. Experiments in ketone bodies demonstrated improved recovery (31%) but only under conditions of low glucose. Similarly, there was enhanced recovery of slices treated with kainic acid (KA, 30 ?M) in reduced glucose media (13-27%), but no difference in normal glucose. These findings suggest that ketone bodies do not alter neuronal function but can alter the response to excitotoxins when energy supplies are impaired, probably by acting as an alternative energy substrate. PMID:25082548

Youssef, Farid F

2015-03-01

358

Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus  

PubMed Central

Hippocampal function and plasticity differ with gender, but the regulatory mechanisms underlying sex differences remain elusive and may be established early in life. The present study sought to elucidate sex differences in hippocampal plasticity under normal developmental conditions and in response to repetitive, predictable versus varied, unpredictable prenatal stress (PS). Adult male and diestrous female offspring of pregnant rats exposed to no stress (control), repetitive stress (PS-restraint), or a randomized sequence of varied stressors (PS-random) during the last week of pregnancy were examined for hippocampal proliferation, neurogenesis, cell death, and local microenvironment using endogenous markers. Regional volume was also estimated by stereology. Control animals had comparable proliferation and regional volume regardless of sex, but females had lower neurogenesis compared to males. Increased cell death and differential hippocampal precursor kinetics both appear to contribute to reduced neurogenesis in females. Reduced local interleukin-1beta (IL-I? immunoreactivity (IR) in females argues for a mechanistic role for the anti-apoptotic cytokine in driving sex differences in cell death. Prenatal stress significantly impacted the hippocampus, with both stress paradigms causing robust decreases in actively proliferating cells in males and females. Several other hippocampal measures were feminized in males such as precursor kinetics, IL-I?-IR density, and cell death, reducing or abolishing some sex differences. The findings expand our understanding of the mechanisms underlying sex differences and highlight the critical role early stress can play on the balance between proliferation, neurogenesis, cell death, and hippocampal microenvironment in adulthood. PMID:18264994

Mandyam, Chitra D.; Crawford, Elena F.; Eisch, Amelia J.; Rivier, Catherine L.; Richardson, Heather N.

2013-01-01

359

Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats  

PubMed Central

Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n?=?128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n?=?54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n?=?64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention. PMID:22768138

Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Rio, Daniele Del; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

2012-01-01

360

Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells  

PubMed Central

Recent observations have suggested that creatine supplementation might have a beneficial effect on glucoregulation in skeletal muscle. However, conclusive studies on the direct effects of creatine on glucose uptake and metabolism are lacking. The objective of this study was to investigate the effects of creatine supplementation on basal and insulin-stimulated glucose transporter (GLUT4) translocation, glucose uptake, glycogen content, glycogen synthesis, lactate production, glucose oxidation and AMP-activated protein kinase (AMPK) phosphorylation in L6 rat skeletal muscle cells. Four treatment groups were studied: control, insulin (100 nm), creatine (0.5 mm) and creatine + insulin. After 48 h of creatine supplementation the creatine and phosphocreatine contents of L6 myoblasts increased by ?9.3- and ?5.1-fold, respectively, but the ATP content of the cells was not affected. Insulin significantly increased 2-deoxyglucose uptake (?1.9-fold), GLUT4 translocation (?1.8-fold), the incorporation of D-[U-14C]glucose into glycogen (?2.3-fold), lactate production (?1.5-fold) and 14CO2 production (?1.5-fold). Creatine neither altered the glycogen and GLUT4 contents of the cells nor the insulin-stimulated rates of 2-DG uptake, GLUT4 translocation, glycogen synthesis and glucose oxidation. However, creatine significantly reduced by ?42% the basal rate of lactate production and increased by ?40% the basal rate of 14CO2 production. This is in agreement with the ?35% increase in citrate synthase activity and also with the ?2-fold increase in the phosphorylation of both ?-1 and ?-2 isoforms of AMPK after creatine supplementation. We conclude that 48 h of creatine supplementation does not alter insulin-stimulated glucose uptake and glucose metabolism; however, it activates AMPK, shifts basal glucose metabolism towards oxidation and reduces lactate production in L6 rat skeletal muscle cells. PMID:14724211

Ceddia, Rolando B; Sweeney, Gary

2004-01-01