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1

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

PubMed

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague-Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5+/-41.9mg/dL) and on GD17 (mean=247.0+/-72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating < or =100microA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm(2), standard error of the mean=+/-0.278) compared with the Ct offspring (8.03mm(2)+/-0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. PMID:20083368

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

2010-01-18

2

Source of inappropriate receptive fields in cortical somatotopic maps from rats that sustained neonatal forelimb removal.  

PubMed

Previously this laboratory demonstrated that forelimb removal at birth in rats results in the invasion of the cuneate nucleus by sciatic nerve axons and the development of cuneothalamic cells with receptive fields that include both the forelimb-stump and the hindlimb. However, unit-cluster recordings from primary somatosensory cortex (SI) of these animals revealed few sites in the forelimb-stump representation where responses to hindlimb stimulation also could be recorded. Recently we reported that hindlimb inputs to the SI forelimb-stump representation are suppressed functionally in neonatally amputated rats and that GABAergic inhibition is involved in this process. The present study was undertaken to assess the role that intracortical projections from the SI hindlimb representation may play in the functional reorganization of the SI forelimb-stump field in these animals. The SI forelimb-stump representation was mapped during gamma-aminobutyric acid (GABA)-receptor blockade, both before and after electrolytic destruction of the SI hindlimb representation. Analysis of eight amputated rats showed that 75.8% of 264 stump recording sites possessed hindlimb receptive fields before destruction of the SI hindlimb. After the lesions, significantly fewer sites (13.2% of 197) were responsive to hindlimb stimulation (P < 0.0001). Electrolytic destruction of the SI lower-jaw representation in four additional control rats with neonatal forelimb amputation did not significantly reduce the percentage of hindlimb-responsive sites in the SI stump field during GABA-receptor blockade (P = 0.98). Similar results were obtained from three manipulated rats in which the SI hindlimb representation was silenced temporarily with a local cobalt chloride injection. Analysis of response latencies to sciatic nerve stimulation in the hindlimb and forelimb-stump representations suggested that the intracortical pathway(s) mediating the hindlimb responses in the forelimb-stump field may be polysynaptic. The mean latency to sciatic nerve stimulation at responsive sites in the GABA-receptor blocked SI stump representation of neonatally amputated rats was significantly longer than that for recording sites in the hindlimb representation [26.3 +/- 8.1 (SD) ms vs. 10.8 +/- 2.4 ms, respectively, P < 0.0001]. These results suggest that hindlimb input to the SI forelimb-stump representation detected in GABA-blocked cortices of neonatally forelimb amputated rats originates primarily from the SI hindlimb representation. PMID:10036265

Lane, R D; Stojic, R S; Killackey, H P; Rhoades, R W

1999-02-01

3

Time-sensitive enhancement of motor learning with the less-affected forelimb after unilateral sensorimotor cortex lesions in rats  

Microsoft Academic Search

Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected ?ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal

J. Edward Hsu; Theresa A. Jones

2005-01-01

4

Changes in forelimb-hindlimb coordination after partial spinal lesions of different extent in the rat.  

PubMed

Forelimb-hindlimb coordination in adult rats moving freely along 2m long runway was investigated using the method of footprint recording. Rats were divided into 3 groups with different extent of spinal lesions (T(9)). Before surgery rats moved with a mean locomotor speed of 73±20 to 96±18cms(-1), stride lengths of 17.5±2.0 to 21.2±2.0cm, and trot like coordination. Early after surgery the locomotor speed and the stride lengths were decreased. The forelimb steps were shorter than hindlimb steps, which led to the occurrence of unpaired forelimb steps. Unpaired steps occurred when the hind paw print lay more than half the hindlimb stride length in front of the ipsilateral paw. The number of unpaired steps was negatively correlated with the difference between the fore- and hindlimb step lengths. The recovery of locomotor speed, stride length, and step sequence patterns took up to 3.5 months depending on the extent of lesion. In the last testings the coordination was characterized by increased distances between ipsilateral footprints leading to a change from an almost synchronized trot to a lesion-dependent walk. This change was accompanied by a switch from the use of both patterns A and C to the most frequent use of the Aa pattern that is better adapted to maintain the body balance. All locomotor changes depended on the extent of the injury of lateral and ventral funiculi. These results demonstrate that footprint analysis can be used for the evaluation of forelimb-hindlimb coordination after spinal lesion in rats. PMID:23142611

Górska, Teresa; Chojnicka-Gittins, Barbara; Majczy?ski, Henryk; Zmys?owski, Wojciech

2012-11-08

5

Loss of Lever Press-Related Firing of Rat Striatal Forelimb Neurons after Repeated Sessions in a Lever Pressing Task  

Microsoft Academic Search

Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from thefloor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive

Regina M. Carelli; Martin Wolske; Mark O. West

1997-01-01

6

A novel method for assessing proximal and distal forelimb function in the rat: the Irvine, Beatties and Bresnahan (IBB) forelimb scale.  

PubMed

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

2010-12-16

7

Decoding rat forelimb movement direction from epidural and intracortical field potentials  

PubMed Central

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

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

2011-01-01

8

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

9

Loss of lever press-related firing of rat striatal forelimb neurons after repeated sessions in a lever pressing task.  

PubMed

Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses. PMID:9030639

Carelli, R M; Wolske, M; West, M O

1997-03-01

10

The structure of skilled forelimb reaching in the rat: a movement rating scale.  

PubMed

Skilled reaching for food is an evolutionary ancient act and is displayed by many animal species, including those in the sister clades of rodents and primates. The video describes a test situation that allows filming of repeated acts of reaching for food by the rat that has been mildly food deprived. A rat is trained to reach through a slot in a holding box for food pellet that it grasps and then places in its mouth for eating. Reaching is accomplished in the main by proximally driven movements of the limb but distal limb movements are used for pronating the paw, grasping the food, and releasing the food into the mouth. Each reach is divided into at least 10 movements of the forelimb and the reaching act is facilitated by postural adjustments. Each of the movements is described and examples of the movements are given from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation. Because the reaching act for the rat is very similar to that displayed by humans and nonhuman primates, the scale can be used for comparative purposes. from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation. Experiments on animals were performed in accordance with the guidelines and regulations set forth by the University of Lethbridge Animal Care Committee in accordance with the regulations of the Canadian Council on Animal Care. The experiment involves training rats to reach for food and then filming the movements used for reaching. 1. Long Evans laboratory rats are mildly deprived of food for 10 days, then adapted to a box containing a slot through which they can reach for food pellets. 2. After about 10 days of training the rats reach consistently and display a preference of one paw. 3. The reaching act is filmed using a high shutter speed (1,000 f/sec) and filming is done from a number of perspectives. 4. The reaching act is then replayed using frame by frame replay. 5. The movements are described in the accompanying video. PMID:19066506

Whishaw, Ian Q; Whishaw, Paul; Gorny, Bogdan

2008-08-08

11

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats.  

PubMed

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

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

2011-02-16

12

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

PubMed Central

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

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

2011-01-01

13

Early overuse and disuse of the affected forelimb after moderately severe intraluminal suture occlusion of the middle cerebral artery in rats  

Microsoft Academic Search

We have previously shown that early forced overuse of the affected forelimb worsens outcome following moderately severe transient focal cortical ischemic stroke in rats using a distal middle cerebral artery occlusion (MCAo) model. This effect may be site-dependent, because we have also found that early forced use of the affected limb after unilateral 6-OHDA induced degeneration of ascending nigrostriatal dopamine

Sondra T. Bland; Rathi N. Pillai; Jaroslaw Aronowski; James C. Grotta; Timothy Schallert

2001-01-01

14

Aging Contributes to Inflammation in Upper Extremity Tendons and Declines in Forelimb Agility in a Rat Model of Upper Extremity Overuse  

PubMed Central

We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.

Kietrys, David M.; Barr-Gillespie, Ann E.; Amin, Mamta; Wade, Christine K.; Popoff, Steve N.; Barbe, Mary F.

2012-01-01

15

Lesion in the lateral cerebellum specifically produces overshooting of the toe trajectory in leading forelimb during obstacle avoidance in the rat.  

PubMed

During locomotion, stepping over an obstacle under visual guidance is crucial to continuous safe walking. Studies of the role of the central nervous system in stepping movements have focused on cerebral cortical areas such as the primary motor cortex and posterior parietal cortex. There is speculation that the lateral cerebellum, which has strong anatomical connections with the cerebral cortex, also plays a key role in stepping movements over an obstacle, although this function of the lateral cerebellum has not yet been elucidated. Here we investigated the role of the lateral cerebellum during obstacle avoidance locomotion in rats with a lateral cerebellar lesion. A unilateral lesion in the lateral cerebellum did not affect limb movements during overground locomotion. Importantly, however, the lesioned animals showed overshooting of the toe trajectory specific to the leading forelimb ipsilateral to the lesion when stepping over an obstacle, and the peak toe position, in which the toe is maximally raised during stepping, shifted away from the upper edge of the obstacle. Recordings of EMG activity from elbow flexor and extensor muscles suggested that the overshooting toe trajectory in the ipsilateral leading forelimb possibly resulted from sustained elbow flexion and delayed elbow extension following prolonged activity of the biceps brachii. These results suggest that the lateral cerebellum specifically contributes to generating appropriate toe trajectories in the ipsilateral leading forelimb and to controlling related muscle activities in stepping over an obstacle, especially when accurate control of the distal extremity is achieved under visual guidance. PMID:23615542

Aoki, Sho; Sato, Yamato; Yanagihara, Dai

2013-04-24

16

Quantitative positron emission tomography imaging of angiogenesis in rats with forelimb ischemia using (68)Ga-NOTA-c(RGDyK).  

PubMed

Gallium-68-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-cyclic Arg-Gly-Asp-D-Tyr-Lys (c(RGDyK)) was developed for ?v?3 targeting, and is a promising agent for imaging of cancer and disorders related to angiogenesis. In this study, we performed kinetic analysis of (68)Ga-NOTA-c(RGDyK) in rats with surgically induced forelimb ischemia, and immunohistochemical analysis was also performed to assess ?v?3 immuno-staining level. Animal models were created by excision of the left brachial vessels, and a sham operation was performed on the right brachial region under 2 % isoflurane anesthesia. Using an animal positron emission tomography/computed tomography (PET/CT) scanner, a list mode PET scan (120 min) was started with the injection of (68)Ga-NOTA-c(RGDyK) via the tail vein at 3, 5 and 7 days after ischemic surgery. Volumes of interest were drawn on the left ventricle, sham operation, control, and ischemic regions. Compartmental and two graphical analyses (Logan and RE plots) were performed for kinetic parameter estimation. The immunohistochemical analysis was also performed after the last PET scan, and cell components were scored on a six point scale for quantification of immuno-staining level (0-negative to 5-very high). A 3-compartment model with reversible binding best described the tissue time-activity curves. The distribution volume of the ischemic region was significantly higher than that of the sham operation (P < 10(-6)) and control region (P < 10(-9)). Both the Logan and RE plots showed high correlation with compartmental analysis (R(2) = 0.96 and 0.95 for Logan and RE, respectively). The temporal changes in distribution volume and binding potential were not significant. The immuno-staining level of the ischemic region was significantly higher than that of sham operation (P < 10(-4)) and control region (P < 10(-8)). Kinetic modeling studies with dynamic (68)Ga-NOTA-c(RGDyK) PET scan are feasible based on an image-derived input function in a rat ischemia model. The kinetic modeling analysis performed in this study will be useful for the quantitative evaluation of (68)Ga-NOTA-c(RGDyK) binding to ?v?3 in angiogenic tissues. PMID:23857293

Kim, Joong Hyun; Kim, Young-Hwa; Kim, Young Joo; Yang, Bo Yeun; Jeong, Jae Min; Youn, Hyewon; Lee, Dong Soo; Lee, Jae Sung

2013-07-16

17

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

PubMed Central

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

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

2007-01-01

18

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

PubMed Central

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

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

2009-01-01

19

Selective forelimb impairment in rats expressing a pathological TDP-43 25?kDa C-terminal fragment to mimic amyotrophic lateral sclerosis.  

PubMed

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

2013-05-21

20

Manipulatory training during early postnatal ontogenesis effects on forelimb preference in food-reaching tasks in albino rats.  

PubMed

The influence of early manipulatory skill training on forepaw preference in adult state of rats was investigated. One group of Wistar rats was trained at the age of 21-28 days of life, another one at the age of 30-37 days of life. Second test of both groups was performed at the age of 120-127 days of life. It was found that after training at the age of 21 days of life adult rats had less expressed predominance in forepaw use and showed ambidextrous tendencies while most rats trained at the age of 30 days of life were lateralised. It is possible to suppose the existence of sensitive formation periods for forepaw preference based on whole organism growth. PMID:23163554

Volnova, Anna; Kurzina, Natalia; Aristova, Irina

2012-11-19

21

Brain Repair in a Unilateral Rat Model of Huntington's Disease: New Insights Into Impairment and Restoration of Forelimb Movement Patterns.  

PubMed

Huntington's disease (HD) produces severe neurodegeneration in the striatum leading to disabling motor impairments, including the loss of control of skilled reaching movements. Fetal GABAergic transplants can physically replace the lost striatal cells but with only partial success in functional recovery. Here, we aimed to determine the extent and quality of the repair produced by fetal cell transplantation through an in-depth analysis of reaching behavior in the quinolinic acid-lesioned rat model of HD. Control, quinolinic acid-lesioned plus sham graft, and quinolinic acid-lesioned plus graft groups of rats were assessed in skilled reaching performance prior to and following lesion surgery and 3 months following injection of 400,000 fetal whole ganglionic eminence-derived cells into the striatum. This was compared to their performance in two more rudimentary tests of motor function (the adjusting step and vibrissae-evoked hand-placing tests). Grafted rats demonstrated a significant improvement in reaching success rate (graft +59%, shamTX +3%). Importantly, the quality of reaching behavior, including all components of the movement, was fully restored with no identifiable differences in the normal behavior shown by control rats. Postmortem immunohistochemical examination verified the survival of large intrastriatal grafts, and Fluoro-Gold tracing indicated appropriate outgrowth to the globus pallidus. Our study illustrates for the first time the detailed analysis of qualitative improvement of motor function following brain repair in a rat model of HD. The results demonstrate significant improvements not only in gross movements but also in the skilled motor patterns lost during HD. Fetal GABAergic cell transplantation showed a demonstrable ability to restore motor function to near normal levels, such that there were few differences from intact control animals, an effect not observed in standard tests of motor function. PMID:23067670

Klein, Alexander; Lane, Emma L; Dunnett, Stephen B

2012-10-12

22

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.

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

2010-01-01

23

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

PubMed

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

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

2013-08-15

24

The bradykinesia assessment task: an automated method to measure forelimb speed in rodents.  

PubMed

Bradykinesia in upper extremities is associated with a wide variety of motor disorders; however, there are few tasks that assay forelimb movement speed in rodent models. This study describes the bradykinesia assessment task, a novel method to quantitatively measure forelimb speed in rats. Rats were trained to reach out through a narrow slot in the cage and rapidly press a lever twice within a predefined time window to receive a food reward. The task provides measurement of multiple parameters of forelimb function, including inter-press interval, number of presses per trial, and success rate. The bradykinesia assessment task represents a significant advancement in evaluating bradykinesia in rat models because it directly measures forelimb speed. The task is fully automated, so a single experimenter can test multiple animals simultaneously with typically in excess of 300 trials each per day, resulting in high statistical power. Several parameters of the task can be modified to adjust difficulty, which permits application to a broad spectrum of motor dysfunction models. Here we show that two distinct models of brain damage, ischemic lesions of primary motor cortex and hemorrhagic lesions of the dorsolateral striatum, cause impairment in all facets of performance measured by the task. The bradykinesia assessment task provides insight into bradykinesia and motor dysfunction in multiple disease models and may be useful in assessing therapies that aim to improve forelimb function following brain damage. PMID:23353133

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

2013-01-23

25

Transplants of embryonic cortical tissue placed in the previously damaged frontal cortex of adult rats: Local cerebral glucose utilization following execution of forelimb movements  

Microsoft Academic Search

Transplantation of fetal cortical tissue into the motor cortex of adult rats was used as an experimental model to examine the functional integration of homotopic fetal neocortical grafts into the motor pathways of adult host brain. We have employed the [14C]2-deoxy-d-glucose method to analyse the metabolic activity of the transplant and host sensorimotor cortex: (i) in animals solicited to perform

A. Ebrahimi-Gaillard; T. Beck; F. Gaillard; A. Wree; M. Roger

1995-01-01

26

Forelimb muscle activity during equine locomotion.  

PubMed

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

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

2012-09-01

27

The Organization of the Forelimb Representation of the C57BL/6 Mouse Motor Cortex as Defined by Intracortical Microstimulation and Cytoarchitecture  

PubMed Central

The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor–somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations.

Adkins, DeAnna L.; Donlan, Nicole A.; Asay, Aaron L.; Thomas, Nagheme; Kleim, Jeffrey A.

2011-01-01

28

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.

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

2009-01-01

29

On the origin of skilled forelimb movements  

Microsoft Academic Search

Homologizing behaviour was once considered unreliable, but the application of modern comparative methods has been shown to provide strong evidence of behavioural homologies. Skilled forelimb movements were thought to originate in the primate lineage but in fact are common among tetrapod taxa and probably share a common origin in early tetrapods. Furthermore, skilled movements are likely to have been derived

Andrew N Iwaniuk; Ian Q Whishaw

2000-01-01

30

SAGE profiling of the forelimb and hindlimb  

Microsoft Academic Search

A recent study has used serial analysis of gene expression to compare mouse forelimb and hindlimb gene-expression profiles. The method successfully identified known regulators of limb identity and has generated a candidate set of differentially expressed genes that may regulate limb identity.

Malcolm Logan

2002-01-01

31

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

2007-11-21

32

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

33

Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats  

Microsoft Academic Search

Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Hyperlipidemic obese Zucker rats develop albuminuria and spontaneous focal glomerulosclerosis (FGS) at an early age, despite normal glomerular capillary pressures and nephron plasma flows. To investigate the role of abnormal lipid metabolism in the pathogenesis of FGS, pharmacologic agents were used to reduce serum lipids in male, obese Zucker rats.

Bertram L Kasiske; Michael P O'donnell; Margot P Cleary; William F Keane

1988-01-01

34

Nitrate-reducing bacteria on rat tongues.  

PubMed Central

Nitrite-producing bacteria (NPB) were isolated from tongues of laboratory rats. The most commonly found nitrite-producing organism was Staphylococcus sciuri, followed by Staphylococcus intermedius, Pasteurella spp., and finally Streptococcus spp. Both morphometric quantification of bacteria on tongue sections and enumeration of culturable bacteria (CFU) showed an increase in the density of bacteria towards the posterior tongue. Up to 65% of bacteria were located in the deep clefts on the posterior tongue. The proportion of culturable NPB in the total culturable microbial population increased from 6% (10(5) CFU cm-2) on the anterior tongue to 65% (10(7) CFU cm-2) on the posterior tongue. Different species compositions of NPB were found on different tongue sections with S. intermedius populations decreasing and S. sciuri and Pasteurella populations increasing towards the posterior tongue. Nitrite production was sensitive to oxygen, and significant nitrite production was only detected on the posterior tongue where the majority of bacteria are situated in deep clefts in the tongue surface. This study suggests the importance of bacteria in nitrite production, from nitrate, on the tongue. Nitrite produced on the tongue may subsequently form nitric oxide in the acidic environment of the stomach. Because of the antimicrobial properties of nitric oxide, a key role for nitrate-reducing tongue bacteria in host animal defense against food-borne pathogens in proposed.

Li, H; Duncan, C; Townend, J; Killham, K; Smith, L M; Johnston, P; Dykhuizen, R; Kelly, D; Golden, M; Benjamin, N; Leifert, C

1997-01-01

35

Prolonged but Delayed Postischemic Hypothermia: A Long-term Outcome Study in the Rat Middle Cerebral Artery Occlusion Model  

Microsoft Academic Search

Delayed but prolonged hypothermia persistently decreases cell death and functional deficits after global cerebral ischemia in rodents. Postischemic hypothermia also reduces infarction after middle cerebral artery occlusion (MCAO) in rat. Because initial neuroprotection is sometimes transient and may not subserve functional recovery, especially on demanding tasks, the authors examined whether postischemic cooling would persistently reduce infarction and forelimb reaching deficits

Frederick Colbourne; Dale Corbett; Zonghang Zhao; Jing Yang; Alastair M. Buchan

2000-01-01

36

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

37

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

Microsoft Academic Search

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

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

2010-01-01

38

Trimethyltin Reduces Recurrent Inhibition in Rats.  

National Technical Information Service (NTIS)

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

R. S. Dyer W. K. Boyes

1984-01-01

39

Nitrate-Reducing Bacteria on Rat Tongues  

Microsoft Academic Search

Nitrite-producing bacteria (NPB) were isolated from tongues of laboratory rats. The most commonly found nitrite-producing organism was Staphylococcus sciuri, followed by Staphylococcus intermedius, Pasteurella spp., and finally Streptococcus spp. Both morphometric quantification of bacteria on tongue sections and enumer- ation of culturable bacteria (CFU) showed an increase in the density of bacteria towards the posterior tongue. Upto65%ofbacteriawerelocatedinthedeepcleftsontheposteriortongue.TheproportionofculturableNPB in the total

HONG LI; CALLUM DUNCAN; JOHN TOWNEND; KENNETH KILLHAM; LORNA M. SMITH; PETER JOHNSTON; ROELF DYKHUIZEN; DENISE KELLY; MICHAEL GOLDEN; NIGEL BENJAMIN; ANDCARLO LEIFERT

1997-01-01

40

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

PubMed Central

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

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

2013-01-01

41

Dimensions of forelimb muscles in orangutans and chimpanzees  

PubMed Central

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

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

2009-01-01

42

Pioglitazone acutely reduces energy metabolism and insulin secretion in rats.  

PubMed

Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity. We assessed glucose homeostasis by hyperinsulinemic-euglycemic and hyperglycemic clamp studies and energy expenditure by indirect calorimetry and biotelemetry in male Wistar and obese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazone (30 mg/kg). In vivo insulin secretion during clamped hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration. Insulin clearance was slightly increased in Wistar but not in ZDF rats. Insulin sensitivity in Wistar rats assessed by the hyperinsulinemic-euglycemic clamp was minimally affected by pioglitazone at this early time point. Pioglitazone also reduced energy expenditure in Wistar rats without altering respiratory exchange ratio or core body temperature. Glucose-induced insulin secretion (GIIS) and oxygen consumption were reduced by pioglitazone in isolated islets and INS832/13 cells. In conclusion, pioglitazone acutely induces whole-body metabolic slowing down and reduces GIIS, the latter being largely independent of the insulin-sensitizing action of the drug. The results suggest that pioglitazone has direct metabolic deceleration effects on the ?-cell that may contribute to its capacity to lower insulinemia and antidiabetic action. PMID:23378607

Lamontagne, Julien; Jalbert-Arsenault, Elise; Pepin, Emilie; Peyot, Marie-Line; Ruderman, Neil B; Nolan, Christopher J; Joly, Erik; Madiraju, S R Murthy; Poitout, Vincent; Prentki, Marc

2013-02-01

43

Lipopolysaccharide reduces sodium intake and sodium excretion in dehydrated rats.  

PubMed

The objective of this study was to find out if lipopolysaccharide (LPS) administered intraperitoneally affects sodium and water intake and renal excretion in dehydrated rats. LPS (0.3-5 mg/kg b.w.) inhibited 0.3M NaCl intake induced by subcutaneous injection of the diuretic furosemide (FURO, 10 mg/kg b.w.) combined with the angiotensin converting enzyme inhibitor, captopril (CAP, 5 mg/kg b.w.). Only the highest doses of LPS (2.5 and 5 mg/kg) inhibited water intake induced by FURO/CAP. LPS (0.6 mg/kg) reduced urinary volume and sodium excretion, but had no effect on mean arterial pressure or heart rate of rats treated with FURO/CAP. LPS (0.3-5.0 mg/kg) abolished intracellular thirst and reduced by 50% the urine sodium concentration of rats that received 2 ml of 2M NaCl by gavage. LPS (0.3-5.0 mg/kg) also reduced thirst in rats treated with FURO alone (10 mg/rat sc). The results suggest that LPS has a preferential, but not exclusive, inhibitory effect on sodium intake and on intracellular thirst. The inhibition of hydro-mineral intake and the antinatriuresis caused by LPS in dehydrated rats may contribute to the multiple effects of the endotoxin on fluid and electrolyte balance and be part of the strategy to cope with infections. PMID:20977913

de Almeida, Roberto L; Constancio, Juliana; Vendramini, Regina C; Fracasso, José F; Menani, José V; De Luca, Laurival A

2010-10-25

44

Similarities and differences between the subchronic and withdrawal effects of clozapine and olanzapine on forelimb force steadiness  

Microsoft Academic Search

The purpose of this study was to compare the subchronic, low-dose effects of clozapine with those of olanzapine in a learned\\u000a behavioral task previously shown to distinguish between clozapine and haloperidol with acute and subchronic treatment regimes.\\u000a Rats were trained to use a single forelimb to press a force-recording operandum and simultaneously to lick water from a dipper\\u000a that remained

John A. Stanford; S. C. Fowler

1997-01-01

45

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

PubMed Central

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

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

2011-01-01

46

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

PubMed

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the ?-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through ?-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

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

2011-03-09

47

Exercise-training reduces BAT thermogenesis in rats.  

PubMed

In the energy balance equation, physical activity represents one component of energy expenditure. From various studies it appears that exercise-training does not affect clearly thermogenesis which depends on brown adipose tissue (BAT) activity. In the present work we examine how exercise-training can influence food intake and body weight regulation in relation to BAT thermogenesis. The proton conductance of the uncoupling protein of BAT was examined in male adult Wistar trained 2 h/day for 20 days and compared to that of sedentary (2 h of fasting instead of exercise) or control animals. All animals were provided with separate sources of the 3 macronutrients (protein, fat and carbohydrate) containing an identical percentage of vitamins, salt mixture and cellulose powder. At the end of training, rats were placed at 5 degrees C during 10 days, then during 4 days at 28 degrees C. This condition has been demonstrated to favour and amplify BAT responsiveness to moderate modifications of stimulation. The body weight of trained rats became significantly lower than that of the control and sedentary rats and this difference persisted all throughout the experiment. When placed at 5 degrees C, all rats increased their total ingestion: control rats enhanced fat intake, while sedentary and trained rats enhanced carbohydrate ingestion. When placed at 28 degrees C, all rats had identical total energy and that of the 3 items intakes. BAT proton conductance was about 40% lower in the trained compared with the sedentary plus the control rats. This indicated a lower BAT thermogenic activity in the trained animals. It could be concluded that exercise-training in rats induces negative energy balance; the reduced BAT activity could restrain weight loss and overeating. PMID:7610127

Larue-Achagiotis, C; Rieth, N; Goubern, M; Laury, M C; Louis-Sylvestre, J

1995-05-01

48

Clenbuterol reduces soleus muscle fatigue during disuse in aged rats.  

PubMed

High levels of clenbuterol have been shown to preserve muscle mass and function during disuse. In this study we report that a low dose of clenbuterol (10 microg/kg per day) lessened the loss of in situ soleus muscle isometric force normalized to wet muscle weight (P(o)/g wet weight) by 8% and reduced isometric fatigue by approximately 30% in senescent rats after 21 days of hindlimb suspension (HS). Clenbuterol did not reduce the loss of relative force in the soleus of adult rats or the plantaris of old or adult rats. Furthermore, clenbuterol failed to improve muscle force or isometric fatigue in the soleus of adult rats or in the plantaris of either age group after HS. We conclude that low levels of clenbuterol reduce muscle fatigue in slow muscles during disuse and this beta-agonist may also have therapeutic value for reducing fatigue in slow muscles (e.g., postural muscles) in the elderly during disuse. PMID:11180204

Chen, K D; Alway, S E

2001-02-01

49

Hypotension and reduced catecholamines in neuropeptide Y transgenic rats.  

PubMed

The neurons that control blood pressure express neuropeptide Y. Administered centrally, this neuropeptide reduces blood pressure and anxiety, together with lowering sympathetic outflow. The generation of neuropeptide Y transgenic rats overexpressing this peptide, under its natural promoter, has allowed us to examine the role of endogenous neuropeptide Y in the long-term control of blood pressure by the sympathetic nervous system. This study tested a hypothesis that endogenous neuropeptide Y acts to reduce blood pressure and catecholamine release. Blood pressure was measured by radiotelemetry in conscious male transgenic and nontransgenic littermates (control). Novel cage with cold water and forced swimming were used as stressors. Catecholamines were determined in 24-hour urine (baseline) and plasma (cold water stress) by a radioenzymatic assay. Blood pressures in baseline and during the stresses were significantly reduced in the transgenic rats. The lower blood pressure was associated with reduced catecholamines, lower decrease in pressure after autonomic ganglionic blockade, and increased longevity. Data obtained through the use of this transgenic rat model support and extend the evidence for the previously postulated sympatholytic and hypotensive effects of neuropeptide Y and provide novel evidence for an important physiological role of endogenous peptide in blood pressure regulation. As indicated by the increased longevity of these rats, in long-term regulation, these buffering actions of neuropeptide Y may have important cardiovascular protective effects against sympathetic hyperexcitation. PMID:12668588

Michalkiewicz, Mieczyslaw; Knestaut, Kriss M; Bytchkova, Elena Yu; Michalkiewicz, Teresa

2003-03-31

50

The comparative anatomy of the forelimb veins of primates.  

PubMed Central

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

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

1989-01-01

51

Transient hypothermia reduces focal ischemic brain injury in the rat.  

PubMed

The effect of transient hypothermia on focal cerebral ischemia was evaluated using a rat model of permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed on 10 rats at a temporalis muscle temperature of 24 degrees C (hypothermic group) and on 10 rats at 36 degrees C (normothermic group). Rats in the hypothermic group were maintained at 24 degrees C for 1 hour after MCA occlusion and then allowed to rewarm to 36 degrees C over the next 2 hours. Animals in both groups were killed 24 hours after MCA occlusion. Cerebral infarcts were visualized by staining of coronal brain sections with 2,3,5-triphenyltetrazolium chloride. Normothermic rats displayed an average infarct volume of 233.1 +/- 13.2 mm3 (standard error of the mean), whereas hypothermic rats had an average infarct volume of 166.2 +/- 22.8 mm3 (P less than 0.01). Expressed as a percentage of the volume of the right hemisphere, the normothermic group had an infarct volume of 22.1 +/- 1.5% and the hypothermic group an infarct volume of 16.0 +/- 2.2% (P less than 0.05). These results demonstrate that transient hypothermia to a temporalis muscle temperature of 24 degrees C significantly reduces subsequent infarct size in an experimental model of permanent arterial occlusion. PMID:1922703

Onesti, S T; Baker, C J; Sun, P P; Solomon, R A

1991-09-01

52

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

53

Paws for thought: comparative radiologic anatomy of the mammalian forelimb.  

PubMed

All mammals share a remarkably similar skeleton based on a common template. This commonality is particularly well illustrated by the versatile pentadactyl limb, upon which all mammalian limbs are based. For most mammals, the primary function of the forelimb is locomotion. The forelimb has been successfully adapted in mammals of all sizes and in terrestrial, arboreal, aquatic, and airborne environments. In primates, the forelimbs have developed such that speed and stamina have been sacrificed for an increased range of movement, which in turn has provided increased manual dexterity. For instance, chimpanzee hands are pronated and the fingers are flexed, and the phalanges are longer and exhibit much more robust insertion areas for flexor tendons. Ungulates (hoofed mammals), on the other hand, have evolved to maximize speed and stamina in quadrupedal locomotion. The two main orders of ungulates have elongated phalanges and metacarpals; all ungulates have lost the first metacarpal. The cat family represents some of the most highly evolved predators. Cats' forelimbs are designed for speed, power, and acceleration rather than for stamina; they maintain all five metacarpals and phalanges, although the first digit is relatively small. PMID:18349453

Gough-Palmer, Antony L; Maclachlan, Jody; Routh, Andrew

54

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats  

PubMed Central

Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ?20% after 5 weeks, with a significant ?60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and ?6?2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced ?4?2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

Bordia, Tanuja; McIntosh, J. Michael

2012-01-01

55

Astaxanthin reduces ischemic brain injury in adult rats  

PubMed Central

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

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

2009-01-01

56

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

PubMed Central

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

Stout, Erik E.

2012-01-01

57

Oral administration of hyaluronan reduces bone turnover in ovariectomized rats.  

PubMed

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

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

2013-01-08

58

Enoxaparin reduces cerebral edemaafter photothrombotic injury in the rat.  

PubMed

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

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

59

Atorvastatin reduces functional deficits caused by photodynamic therapy in rats.  

PubMed

Clinical studies have indicated that photodynamic therapy (PDT) significantly prolonged the median survival of patients with gliomas. Experimental studies demonstrate that increasing optical energy and photosensitizer dose leads to increased volume of tumor necrosis. However, increasing the light dose delivered to the tumor may increase the risks of inducing permanent neurological deficits. In the current study, we sought to test the behavioral deficits induced in normal rats by brain PDT and the neurorestorative effects of atorvastatin on PDT-induced behavioral deficits. Considering its potential as a combination treatment of brain tumors, we investigated both in vitro and in vivo whether atorvastatin treatment promotes brain tumor growth. Non-tumored Fischer rats received PDT (n=18). Nine of the PDT-treated animals were treated with atorvastatin. Control animals underwent the same surgical procedure, but did not receive Photofrin and laser light. PDT-treated animals had significant behavioral deficits on days 2, 5, 7, 9 and 14 after PDT, compared with surgery controls. PDT-treated animals receiving atorvastatin displayed significantly ameliorated behavioral deficits on days 7, 9 and 14 after PDT, compared to PDT-treated rats. In vitro tumor cell viability and growth were evaluated. Atorvastatin did not affect the growth of glioma cells. Fischer rats with intracranial 7-day-old 9L glioma tumor cell implantation were randomly subjected to no treatment, PDT alone, atorvastatin alone, or combined treatment with atorvastatin and PDT (6 rats/group). Our data indicate that atorvastatin did not promote tumor growth in either PDT treated and non-treated rats. However, atorvastatin significantly reduced the cell damage caused by PDT. To further test the mechanisms underlying the atorvastatin-mediated reduction of functional deficits, we investigated the effects of atorvastatin on angiogenesis and synaptogenesis. Our data demonstrate that atorvastatin significantly induced angiogenesis and synaptogenesis in the PDT-damaged brain tissue. Our data indicate that PDT induces functional deficits. Atorvastatin treatment promotes functional restoration after PDT, but does not promote glioma growth in vitro and in vivo. Atorvastatin reduces astrocyte and endothelial cell damage caused by PDT and induces angiogenesis and synaptogenesis after PDT. Thus consideration and further testing of the combination of atorvastatin and PDT for the treatment of glioma is warranted. PMID:21850369

Zheng, Xuguang; Chopp, Michael; Lu, Yong; Jiang, James; Zhao, Danping; Ding, Christopher; Yang, Hongyan; Zhang, Li; Jiang, Feng

2011-08-17

60

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

61

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

PubMed

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

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

2012-10-29

62

Acetyl-L-carnitine reduces impulsive behaviour in adolescent rats.  

PubMed

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 two nose-poking holes, one delivering one food pellet immediately, and the other five pellets after a delay. Delay length was increased over days (from 0 to 80 s). Individual differences in the preference-delay curve emerged, with the identification of two distinct subpopulations, i.e. one with a nearly horizontal curve and another with a very steep ("impulsive") slope. The impulsivity profile was slightly but consistently reduced by chronic ALC administration. Consistent results were also obtained with methylphenidate (MPH, saline or 3 mg/kg IP twice daily). Impulsive rats exhibited a lower metabolite/serotonin (5HIAA/5HT) ratio in the medial frontal cortex (MFC) and lower noradrenaline (NA) levels in the MFC and cingulate cortex (CC) when compared with the other subgroup. The ALC treatment increased NA levels in the CC and the 5HIAA/5HT ratio in both CC and MFC. Present data suggest that ALC, a drug devoid of psychostimulant properties, may have some beneficial effects in the treatment of ADHD children. PMID:15138763

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

2004-05-08

63

Ancestry of motor innervation to pectoral fin and forelimb  

Microsoft Academic Search

Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned

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

2010-01-01

64

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

PubMed

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

Halenar, Lauren B

2011-11-01

65

Aspiration of a cervical spinal contusion injury in preparation for delayed peripheral nerve grafting does not impair forelimb behavior or axon regeneration  

PubMed Central

A peripheral nerve graft model was used to examine axonal growth after a unilateral cervical (C) contusion injury in adult rats and to determine if manipulation of an injury site prior to transplantation affects spontaneous behavioral recovery. After a short delay (7d) the epicenter of a C4 contusion was exposed and aspirated without harming the cavity walls followed by apposition with one end of a predegenerated tibial nerve to the rostral cavity wall. After a longer delay (28d) the aspirated cavity was treated with GDNF to promote regeneration by chronically injured neurons. In both groups forelimb and hindlimb locomotor scores decreased significantly 2d after lesion site manipulation, but by 7d, the forelimb score was not different from the pre-manipulation score. There was no significant difference in grid walking or grip strength scores for the affected forelimb in either group 7d after contusion vs. 7d after manipulation. Over 1500 brain stem and propriospinal neurons grew axons into the graft with either delay. These results demonstrate that a contusion injury site can be manipulated prior to transplantation without causing long-lasting forelimb or hindlimb behavioral deficits and that peripheral nerve grafts support axonal growth after acute or chronic contusion injury.

Sandrow, Harra R.; Shumsky, Jed S.; Amin, Arthi; Houle, John D.

2008-01-01

66

Dietary restriction and nicotine can reduce anxiety in female rats.  

PubMed

Anxiety may play a role in the initiation of smoking and there is evidence to suggest that sex and age may predetermine responses to nicotine. At present, the greatest increase in smoking is in women and it is often accompanied by dieting. The purpose of the present study was to investigate how the impact of dietary restriction might modify the effects of nicotine in female adult and adolescent rats. The effects of nicotine in the elevated plus-maze test of anxiety were compared in free-feeding animals and those subjected to dietary restriction that reduced body weight to 85% of free-feeding weight. In nondeprived adult females, nicotine (0.05-0.5 mg/kg, s.c.) reduced the percentage of time spent on the open arms, indicating anxiogenic effects. However, the effects of nicotine were dramatically changed in food-restricted adult females and 0.05 mg/kg had a striking anxiolytic effect. No significant effects of nicotine were found in the adolescent female rats, suggesting a role of circulating sex hormones in modulating nicotine's effects on anxiety. However, in the adolescent females, dietary restriction significantly increased the percentages of time spent and entries onto the open arms, without changing closed arm entries, indicating an anxiolytic effect. These results raise the important possibility that, in prepubertal girls, dietary restriction may have anxiolytic effects and this might contribute to the onset of anorexia. Circulating female hormones reduce this effect, but in adult females the combination of dietary restriction and nicotine may have important anxiolytic effects that impact on the initiation of regular smoking. PMID:12700683

Genn, Rachel F; Tucci, Sonia; Edwards, Jessica E; File, Sandra E

2003-04-09

67

Reduced intravenous toxicity of amiodarone nanosuspension in mice and rats.  

PubMed

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

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

2012-09-06

68

Unilateral forelimb partial aphalangia in a kitten.  

PubMed

Congenital limb deformities are rarely reported in the cat. The macroscopic and radiographic features of aphalangia are described in a 2-month-old male kitten showing a shortened limb that ended, at the level of the carpus, in a stump without digits. A nail was present at the level of the first phalanx and on the palmar surface only two footpads were present. The radiographs showed an absence of phalanges. The first metacarpal and the proximal and distal phalanges of digit 1 were present. The deformed metacarpal bones were reduced in length; the carpal bones were incompletely ossified. This defect is a rare condition in many animal species. To the author's knowledge, the congenital fore limb deformity described here is the first documented case in a cat. PMID:22412165

Macrì, Francesco; Lanteri, Giovanni; Rapisarda, Giuseppe; Marino, Fabio

2012-01-06

69

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

PubMed

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

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

2007-06-01

70

Peripheral Nerve Injury in Developing Rats Reorganizes Motor Cortex.  

National Technical Information Service (NTIS)

We investigated the effect of neonatal nerve leisons 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...

J. P. Donoghue J. N. Sanes

1986-01-01

71

COPPER DEFICIENCY REDUCES IRON ABSORPTION AND BIOLOGICAL HALF-LIFE IN MALE RATS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Dietary copper deficiency (CuD) in rats leads to iron (Fe) deficiency anemia. Is this because CuD reduces Fe absorption? Fe absorption in CuD rats was determined by feeding 59Fe and using whole-body counting (WBC) to assess the amount retained over time. Two groups, each with 45 male weanling rats, ...

72

PITX2 gain-of-function induced defects in mouse forelimb development  

Microsoft Academic Search

BACKGROUND: Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and

Johan Holmberg; Gorel Ingner; Curt Johansson; Peter Leander; Tord A Hjalt

2008-01-01

73

Patterns of correlation and covariation of anthropoid distal forelimb segments correspond to Hoxd expression territories  

Microsoft Academic Search

Anthropoids in general and hominoids in particular exhibit differential adapta- tions in forearm and digital skeletal proportions to a diverse array of locomotor modes. Hox genes act as selector genes with spatially regulated expression patterns during development. Their expression in the forelimb appears to define modules that specify differential skeletal growth. Here we explore forelimb skeletal proportions in a large

Philip L. Reno; Melanie A. McCollum; Martin J. Cohn; Richard S. Meindl; Mark Hamrick; C. Owen Lovejoy

2008-01-01

74

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.

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

2012-01-01

75

DIETARY COPPER DEFICIENY REDUCES IRON ABSORPTION AND DUODENAL ENTEROCYTE HEPHAESTIN PROTEIN IN MALE AND FEMALE RATS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Dietary copper (Cu) deficiency reduces iron (Fe) in male rats, but whether this occurs in female rats has been questioned. The mechanism for reduced Fe absorption in Cu deficiency is unknown, but may involve the intestinal Cu-dependent ferroxidase Dephaestin (Hp). A 2 x 2 factorial experiment was de...

76

Melatonin reduces oxidative damage induced by aluminium in rat kidney  

Microsoft Academic Search

We evaluated the effect of melatonin (Mel), in male Wistar rats which received aluminium (Al) lactate for 12 weeks (0.57mg Al\\/100g body weight (b.w.), i.p. three times per week). Moreover rats received Mel (10mg\\/kg b.w. i.p. 5 days\\/weeks) for 12 weeks. At the end of the treatment water and sodium balances were studied, and nephrogenic cyclic adenosine monophosphate (cAMP) was

Stella Mahieu; María del Carmen Contini; Marcela González; Néstor Millen

2009-01-01

77

Reduced strength of rat cortical bone after glucocorticoid treatment  

Microsoft Academic Search

Summary  The aim of the present study was to examine the effect of therapeutic doses of glucocorticoids on the mechanical strength\\u000a of rat femora. Groups of rats were treated with a glucocorticoid —methylprednisolone (Solu-Medrol)—1 mg\\/kg\\/day for 5, 10,\\u000a 30, and 90 days. One group served as intact control, two control groups were injected with saline for 30 and 90 days and

Gitte Ørtoft; Hans Oxlund

1988-01-01

78

Forelimb myology of the pygmy hippopotamus (Choeropsis liberiensis).  

PubMed

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

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

2007-06-01

79

Forelimb proportions and kinematics: how are small primates different from other small mammals?  

PubMed

The crouched limb posture of small mammals enables them to react to unexpected irregularities in the support. Small arboreal primates would benefit from these kinematics in their arboreal habitat but it has been demonstrated that primates display certain differences in forelimb kinematics to other mammals. The objective of this paper is to find out whether these changes in forelimb kinematics are related to changes in body size and limb proportions. As primates descended from small ancestors, a comparison between living small primates and other small mammals makes it possible to determine the polarity of character transformations for kinematic and morphometric features proposed to be unique to primates. Walking kinematics of mouse lemurs, brown lemurs, cotton-top tamarins and squirrel monkeys was investigated using cineradiography. Morphometry was conducted on a sample of 110 mammals comprising of primates, marsupials, rodents and carnivores. It has been shown that forelimb kinematics change with increasing body size in such a way that limb protraction increases but retraction decreases. Total forelimb excursion, therefore, is almost independent of body size. Kinematic changes are linked to changes in forelimb proportions towards greater asymmetry between scapula and radius. Due to the spatial restriction inherent in the diagonal footfall sequence of primates, forelimb excursion is influenced by the excursion of the elongated hind limb. Hindlimb geometry, however, is highly conserved, as has been previously shown. The initial changes in forelimb kinematics might, therefore, be explained as solutions to a constraint rather than as adaptations to the particular demands of arboreal locomotion. PMID:19043050

Schmidt, Manuela

2008-12-01

80

Endotoxin-induced mortality in rats is reduced by nitrones  

SciTech Connect

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

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

1989-12-01

81

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

2012-12-12

82

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

Microsoft Academic Search

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

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

83

Evening primrose oil reduces urinary calcium excretion in both normal and hypercalciuric rats  

Microsoft Academic Search

Hypercalciuria is an important risk factor in the aetiology of idiopathic urolithiasis and many treatment modalities in clinical practice are directed towards reducing urinary calcium excreation. There are no natural animal models of hypercalciuria, such as the spontaneous hypertensive rat; however, the streptozotocin-diabetic rat is accepted as a good model for studies of disordered renal function associated with diabetes mellitus.

I. Tulloch; W. S. A. Smellie; A. C. Buck

1994-01-01

84

Vitamin D Deficiency and Ovariectomy Reduced the Strength of the Femoral Neck in Rats  

Microsoft Academic Search

Vitamin D (vit D) deficiency is common in the elderly, and the aim of this study was to investigate whether vit D deprivation in ovariectomized (ovx) and normal rats would reduce fracture strength. Forty mature female Wistar rats were randomized into four groups: two were ovariectomized (ovx) and two were sham-operated (sham). One ovx and one sham group were fed

T. S. Kaastad; O. Reiker s; V. Halvorsen; J. A. Falch; K. J. Obrant; L. Nordsletten

2001-01-01

85

Renal osteodystrophy in rats with reduced renal mass  

Microsoft Academic Search

The rat remnant kidney, a popular model of experimental renal failure, has also been used to assess the histological bone changes associated with reduction in renal mass. The suitability of this model has been challenged, especially with regard to the standardiza- tion of animals from different age groups and various degrees of renal failure. The present study was under- taken:

A. Moscovici; J. Bernheim; M. M. Popovtzer; D. Rubinger

1996-01-01

86

Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats  

Microsoft Academic Search

Background\\/Aims: Hepatic fibrosis occurs as a result of injury to the liver parenchyma and biliary system. We have studied the effect of the traditional Chinese medicinal herb, Salvia miltiorrhiza, in an experimental model of hepatic fibrosis and evaluated its effect on various paradigms involved in hepatic fibrosis.Methods: Liver fibrosis was induced in male Wistar rats by chronic administration of carbon

Shanthi Wasser; Jean May Sian Ho; Hui Kheng Ang; Carolyn Eng Looi Tan

1998-01-01

87

Immediate Postsession Feeding Reduces Operant Responding in Rats  

ERIC Educational Resources Information Center

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

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

2012-01-01

88

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

89

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

PubMed

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

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

2013-08-27

90

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

Microsoft Academic Search

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

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

2000-01-01

91

Long-term enalapril and verapamil in rats with reduced renal mass  

Microsoft Academic Search

Long-term enalapril and verapamil in rats with reduced renal mass.The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria

Felix P Brunner; Gilbert Thiel; Monika Hermle; H Andreas Bock; Michael J Mihatsch

1989-01-01

92

IL10 reduces rat brain injury following focal stroke  

Microsoft Academic Search

The effects of the anti-inflammatory cytokine, IL-10, on brain injury following permanent focal ischemia were determined. Rats subjected to occlusion of the right middle cerebral artery (MCAO) were administered IL-10 (1 ?g) centrally into the lateral ventricle 30 min and 3 h post MCAO or systemically into the tail vein (5 or 15 ?g\\/h) starting 30 min post MCAO for

Patricia A. Spera; Julie A. Ellison; Giora Z. Feuerstein; Frank C. Barone

1998-01-01

93

Interleukin 10 reduces the severity of acute pancreatitis in rats  

Microsoft Academic Search

BACKGROUND & AIMS: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease.METHODS: Eighty-four Sprague-Dawley rats were divided into four groups. Group

AJ Rongione; AM Kusske; K Kwan; SW Ashley; HA Reber; DW McFadden

1997-01-01

94

Arginine administration reduces creatine kinase activity in rat cerebellum  

Microsoft Academic Search

In the present study was evaluated the in vivoeffects of arginine administration on creatine kinase (CK) activity in cerebellum of rats. We also tested the influence of\\u000a antioxidants, namely ?-tocopherol and ascorbic acid and the nitric oxide sinthase inhibitor, N?-nitro-L-arginine methyl ester (L-NAME), on the effects elicited by Arg in order to investigate the possible participation\\u000a of nitric oxide (NO)

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

2007-01-01

95

Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats  

Microsoft Academic Search

Background and aims Lipid peroxidation is believed to be involved in the pathophysiology of a number of diseases and in the process of aging.\\u000a This study investigates the effects of dietary supplementation with vitamin E (20 g\\/kg diet of all-rac-?-tocopheryl succinate\\u000a for 3 weeks) on both non-enzymatic and enzymatic lipid peroxidation in experimental rats with carbon tetrachloride (CCl4)-induced hepatotoxicity (2.5

E. Södergren; J. Cederberg; B. Vessby; S. Basu

2001-01-01

96

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

97

PITX2 gain-of-function induced defects in mouse forelimb development  

PubMed Central

Background Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle. Results To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis. Conclusion Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis.

Holmberg, Johan; Ingner, Gorel; Johansson, Curt; Leander, Peter; Hjalt, Tord A

2008-01-01

98

Axial Hox9 activity establishes the posterior field in the developing forelimb  

PubMed Central

Current models hold that the early limb field becomes polarized into anterior and posterior domains by the opposing activities of Hand2 and Gli3. This polarization is essential for the initiation of Shh expression in the posterior margin of the limb bud, but how this polarity is established is not clear. Here we show that initial anteroposterior polarization of the early forelimb field requires the function of all four Hox9 paralogs (Hoxa9, Hoxb9, Hoxc9, and Hoxd9). This is unexpected, given that only HoxA and HoxD AbdB group genes have been shown to play a role in forelimb patterning, regulating the activation and maintenance of Shh expression and subsequent proximal-distal patterning of the forelimb. Our analysis of Hox9 quadruple mutants demonstrates that Hox9 function is required for the expression of Hand2 in the posterior limb field. Subsequently, Gli3 expression is not repressed posteriorly, Shh expression is not initiated, and collinear expression of HoxA/D10–13 is not established, resulting in severely malformed forelimbs lacking all posterior, Shh-regulated elements. This Hox9 mutant phenotype is restricted to the forelimbs; mutant hindlimbs are normal, revealing fundamental differences in the patterning mechanisms governing the establishment of forelimb and hindlimb fields.

Xu, Ben; Wellik, Deneen M.

2011-01-01

99

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

PubMed Central

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

Choi, Hyu Jin; Kim, Kyoung Beom

2011-01-01

100

Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats.  

PubMed

Erythropoietin (EPO) has been shown to be neuroprotective in various models of neuronal injury. The aim of the present study was to investigate the beneficial effect of recombinant human EPO (rhEPO) following intracerebral hemorrhage (ICH) and the underlying molecular and cellular mechanisms. ICH was induced using autologous blood injection in adult rats. rhEPO (5000 IU/kg) or vehicle was administered to rats with ICH 2 h following surgery and every 24 h for 1 or 3 days. To study the involvement of the PI3K signaling pathway in the rhEPO?mediated effect, the PI3K inhibitor wortmannin (15 µg/kg), was intravenously administered to rats with ICH 90 min prior to rhEPO treatment. Brain edema was measured 3 days following ICH and behavioral outcomes were measured at 1, 7, 14, 21 and 28 days following ICH using the modified neurological severity score (mNSS) and the corner turn test. Proinflammatory cytokines, including tumor necrosis factor (TNF)??, interleukin (IL)?1? and IL?6, in the ipsilateral striatum were analyzed using an enzyme?linked immunosorbent assay 24 h following ICH. Neuronal apoptosis in the perihematomal area was determined by NeuN and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) double?staining. The results showed that rhEPO treatment reversed ICH, increased brain water content, upregulated proinflammatory cytokines, neuronal loss and apoptosis in the perihematomal area and rescued behavioral deficits in injured rats. Inhibiting the PI3K pathway with wortmannin abolished the rhEPO?mediated neuroprotective effects. Moreover, western blot analysis showed that rhEPO induced the upregulation of Akt phosphorylation and downregulation of glycogen synthase kinase (GSK)?3? phosphorylation, which were reversed by pretreatment with wortmannin, indicating the involvement of PI3K signaling in rhEPO-mediated anti?apoptotic and anti?inflammatory effects following ICH. In conclusion, these results suggested that rhEPO may exert its beneficial effects in ICH through the activation of the PI3K signaling pathway. PMID:24008820

Yu, Zhen; Tang, Ling; Chen, Lifen; Li, Jinfang; Wu, Wanfu; Hu, Changlin

2013-09-04

101

Ancestry of motor innervation to pectoral fin and forelimb.  

PubMed

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

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

2010-07-27

102

Energetics of swimming by the ferret: consequences of forelimb paddling.  

PubMed

The domestic ferret (Mustela putorius furo) swims by alternate strokes of the forelimbs. This pectoral paddling is rare among semi-aquatic mammals. The energetic implications of swimming by pectoral paddling were examined by kinematic analysis and measurement of oxygen consumption. Ferrets maintained a constant stroke frequency, but increased swimming speed by increasing stroke amplitude. The ratio of swimming velocity to foot stroke velocity was low, indicating a low propulsive efficiency. Metabolic rate increased linearly with increasing speed. The cost of transport decreased with increasing swimming speed to a minimum of 3.59+/-0.28 J N(-1) m(-1) at U=0.44 m s(-1). The minimum cost of transport for the ferret was greater than values for semi-aquatic mammals using hind limb paddling, but lower than the minimum cost of transport for the closely related quadrupedally paddling mink. Differences in energetic performance may be due to the amount of muscle recruited for propulsion and the interrelationship hydrodynamic drag and interference between flow over the body surface and flow induced by propulsive appendages. PMID:16861018

Fish, Frank E; Baudinette, Russell V

2006-06-21

103

Evidence that high-sucrose diet reduces dentin formation and disturbs mineralization in rat molars.  

PubMed

In addition to its caries-promoting effect, a high-sucrose diet reduces the apposition of mineralized dentin in young rats. This study was undertaken to test whether it has a similar effect on the width of the as-yet-uncalcified matrix, predentin. Female Wistar rats were weaned at the age of 3 weeks and fed for 7 weeks with either a high-sucrose diet, a non-cariogenic raw potato starch diet, or a non-cariogenic commercial powdered rat food (for reference). The sucrose diet induced the greatest number of caries lesions. Dentin formation was smaller and the predentin zone wider in rats fed a sucrose diet when compared with rats fed the reference diet. In rats fed a starch diet, dentin formation was smaller than in rats fed a reference diet, but no alterations in the areas of caries lesions or predentin width were observed. Widening of the predentin zone in rats fed a high-sucrose diet may reflect changes in odontoblast function, such as reduced matrix synthesis and possibly disturbed mineralization. Dentinal caries progression may thus be modulated by odontoblast function, not as much by matrix formation but rather by mineralization. PMID:8600187

Hietala, E L; Larmas, M

1995-12-01

104

Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.  

PubMed

Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. PMID:20816923

Ho, Y C; Wang, S

2010-09-17

105

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

PubMed Central

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

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

2009-01-01

106

Protective Effect of Reduced Glutathione on Acute Reflux Pancreatitis in the Rat  

Microsoft Academic Search

The possible beneficial effect of reduced glutathione infusion on acute reflux pancreatitis was investigated in five groups of rats (8 each). In groups A, A’ and B, B’ acute pancreatitis was induced by means of a closed duodenal loop; group C was sham operated. In groups B and B’ reduced glutathione was infused at a flow rate of 0.2 ml\\/h

Daniela Basso; Maria Piera Panozzo; Carlo Fabris; Aldo Infantino; Mario Plebani; Donatello Olivato; Ambrogio Fassina; Giuseppe Del Favero

1993-01-01

107

The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required  

Microsoft Academic Search

Metabolic pathways underlying the regeneration of reduced glutathione were investigated in acutely isolated metabolically active mitochondria from rat forebrain. The application of hydrogen peroxide to the organelles was accompanied by a transient increase in glutathione disulfide. The recovery of reduced glutathione was significantly improved in the presence of alternatively succinate, malate, citrate, isocitrate, or ?-hydroxybutyrate. Inhibition of succinate dehydrogenase by

Roland Vogel; Heinrich Wiesinger; Bernd Hamprecht; Ralf Dringen

1999-01-01

108

Evidence that High-sucrose Diet Reduces Dentin Formation and Disturbs Mineralization in Rat Molars  

Microsoft Academic Search

In addition to its caries-promoting effect, a high-sucrose diet reduces the apposition of mineralized dentin in young rats. This study was undertaken to test whether it has a similar effect on the width of the as-yet-uncalcified matrix, predentin. Female Wistar rats were weaned at the age of 3 weeks and fed for 7 weeks with either a high-sucrose diet, a

E.-L. Hietala; M. Larmas

1995-01-01

109

Intracerebroventricular administration of cholecystokinin reduces stereotypy in dopamine-supersensitive rats.  

PubMed

Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 microliters) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. Experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icv and long-term saline-treated rats that received CCK-8 (SCCK, N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 +/- 1.7 vs 31 +/- 1.6; P < 0.05) and CCK-8 significantly reduced stereotyped behavior in supersensitive rats (42 +/- 1.7 vs 37 +/- 1.5; P < 0.05). These results show that CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8. PMID:8520531

Tieppo, C A; Silva, A M; Palermo-Neto, J; Nasello, A G; Felicio, L F

1995-03-01

110

Oxyntomodulin Reduces Hydromineral Transport Through Rat Small Intestine  

Microsoft Academic Search

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

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

1998-01-01

111

Red maca (Lepidium meyenii) reduced prostate size in rats  

Microsoft Academic Search

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

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

2005-01-01

112

Sildenafil and glyceryl trinitrate reduce tactile allodynia in streptozotocin-injected rats.  

PubMed

The possible antiallodynic effect of phosphodiesterase 5 inhibitor sildenafil and nitric oxide donor glyceryl trinitrate as well as the changes in phosphodiesterase 5A2 mRNA expression in dorsal root ganglion and spinal cord of allodynic diabetic rats was assessed. Diabetes was induced by streptozotocin (50mg/kg, i.p.) in male Wistar rats. Streptozotocin injection produced hyperlglycemia, polydipsia, polyphagia and polyuria as well as long-term tactile allodynia (12 weeks) and a reduction of phosphodiesterase 5A2 mRNA expression in spinal cord of diabetic rats. Systemic administration of sildenafil (1-5.6 mg/kg, i.p.) reduced tactile allodynia in a dose-dependent manner in diabetic rats. Likewise, glyceryl trinitrate patches (0.2mg/h) also reduced tactile allodynia in diabetic rats. Moreover, both drugs reversed streptozotocin-induced phosphodiesterase 5A2 mRNA expression reduction. Our results indicate that glyceryl trinitrate and sildenafil reduce tactile allodynia in diabetic rats suggesting that nitric oxide and cyclic GMP supply is an important step in their mechanism of action of these drugs in diabetic animals. Data suggest that nitric oxide donors (as glyceryl trinitrate) and drugs which increase cyclic GMP levels (as sildenafil) could have a role in the pharmacotherapy of tactile allodynia in diabetic patients. PMID:20079349

Araiza-Saldaña, Claudia I; Rocha-González, Héctor I; Ambriz-Tututi, Mónica; Castañeda-Corral, Gabriela; Caram-Salas, Nadia L; Hong, Enrique; Granados-Soto, Vinicio

2010-01-13

113

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats.  

PubMed

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly reduced portal pressures (24 +/- 1 vs 32 +/- 1 cm saline), macroscopic mucosal damage (24 +/- 1 vs 39 +/- 4% of mucosa), and histologic deep necrosis (36 +/- 2 vs 61 +/- 4% of mucosal length). Increased dosage of propranolol to 4 mg did not produce any further reduction of portal pressure or mucosal damage. Central venous and systemic arterial pressures were not significantly altered by propranolol. The extent of mucosal damage correlated with levels of portal pressure (P less than 0.01) in portal hypertensive rats. Sham-operated normotensive rats had less macroscopic mucosal damage (26 +/- 4%) than portal hypertensive rats, and propranolol did not affect the extent of ethanol-induced damage or portal pressures in these animals. We conclude: (1) Propranolol is effective in reducing extent of ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in sham-operated controls; (2) this effect correlates with reduction of portal pressure; and (3) our study supports the clinical impression that reducing portal pressure may be one approach for the prevention and therapy of gastric mucosal damage in portal hypertension. PMID:3943443

Sankary, H; Sarfeh, I J; Tarnawski, A; Maeda, R; Ivey, K J; Mason, G R

1986-02-01

114

Sleep deprivation reduces neuroglobin immunoreactivity in the rat brain.  

PubMed

Neuroglobin (Ngb), a protein located in the mammal's brain, is involved in oxygen transport and free radical scavenging inside the neurons. Ngb colocalizes with choline acetyltransferase in the laterodorsal tegmental nucleus and in the pontine tegmental nucleus, both involved in the sleep-wake cycle regulation. Some studies have shown that free radicals accumulated during prolonged wakefulness are removed during sleep. Therefore, Ngb could act as a regulator of free radicals generated during prolonged wakefulness in the brain. The aim of this study was to determine whether prolonged wakefulness affects Ngb immunoreactivity because of increases in the oxidative stress induced by continuous neuronal activity. For this purpose, male adult Wistar rats were implanted with electrodes for sleep recordings and were divided into control and sleep-deprived groups. Sleep deprivation was carried out for 24 h by gentle handling of the animals. Sleep-wake activity was determined during the deprivation period or 24?h of control conditions. Subsequently, both groups of animals were killed and their brains were obtained and processed for Ngb immunohistochemical analysis and detection of lipid peroxidation. Our data found no evidence of increased oxidative stress in the brains of sleep-deprived animals compared with the controls. The number of Ngb-positive cells was decreased in the sleep-deprived animals in all analyzed areas of the brain compared with the control group. Our results suggest that Ngb could be involved in sleep regulation, independent of its role in the control of oxidative stress. PMID:23262504

Melgarejo-Gutiérrez, Montserrat; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Escobar, Carolina; Santiago-García, Juan; Garcia-Garcia, Fabio

2013-02-13

115

Chlorzoxazone, an SK channel activator used in humans, reduces excessive alcohol intake in rats  

PubMed Central

Background Alcoholism imposes a tremendous social and economic burden. There are relatively few pharmacological treatments for alcoholism, with only moderate efficacy, and there is considerable interest in identifying additional therapeutic options. Alcohol exposure alters SK-type potassium channel (SK) function in limbic brain regions. Thus, positive SK modulators such as chlorzoxazone (CZX), an FDA-approved centrally-acting myorelaxant, might enhance SK function and decrease neuronal activity, resulting in reduced alcohol intake. Methods We examined whether CZX reduced alcohol consumption under two-bottle choice (20% alcohol and water) in rats with intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In addition, we used ex vivo electrophysiology to determine whether SK inhibition and activation can alter firing of nucleus accumbens (NAcb) core medium spiny neurons. Results CZX significantly and dose-dependently decreased alcohol but not water intake in IAA rats, with no effects in CAA rats. CZX also reduced alcohol preference in IAA but not CAA rats, and reduced the tendency for rapid initial alcohol consumption in IAA rats. CZX reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and greater CZX inhibition of firing in IAA versus CAA rats. Conclusions The potent CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more moderate intake in CAA rats, may reflect the greater CZX reduction in IAA NAcb core firing observed ex vivo. Thus, CZX could represent a novel and immediately accessible pharmacotherapeutic intervention for human alcoholism.

Hopf, F. Woodward; Simms, Jeffrey A.; Chang, Shao-Ju; Seif, Taban; Bartlett, Selena E.; Bonci, Antonello

2010-01-01

116

Calcium supplementation efficiently reduces lead absorption in suckling rats.  

PubMed

The effect of calcium supplementation on tissue lead was evaluated in suckling Wistar rats. Such data are not yet available in the literature. The following artificial feeding regimen was used for calcium supplementation: cow's milk by addition of 1%, 3% or 6% Ca as CaHPO(4)x2H(2)O suspension to increase the daily calcium intake about 1.4, 2 or 3 times above control values. Artificial feeding was applied during 7 hr each day for nine consecutive days (from day 6 through 15 after birth). The effect of such treatment on lead absorption and elimination was evaluated in two separate experiments: calcium supplementation during oral lead exposure (as acetate; daily dose 2 mg Pb/kg body wt.; total Pb dose 18 mg/kg body wt.) or after a single intraperitoneal lead administration (5 mg/kg body wt.). At the end of experiments, lead in tissues (liver, kidneys, brain and carcass), and essential elements (Ca, Fe, Zn, Cu) were analysed by atomic absorption spectrometry. Calcium supplementation caused a statistically significant decrease of lead in all tissues of sucklings orally exposed to lead. This decrease was dose-related being about 1.3, 1.5 and 2 times lower in groups supplemented with 1%, 3%, or 6% calcium compared to controls, respectively. Increased calcium intake had no effect on incorporated lead after parenteral lead exposure. Calcium supplementation increased carcass calcium and had no effect on trace elements in tissues, pups' general appearance and body weight gain. It is concluded that higher calcium intake might be a way of efficient reduction of lead absorption during the suckling period. PMID:11903960

Varnai, V M; Piasek, M; Blanusa, M; Sari?, M M; Simi?, D; Kostial, K

2001-12-01

117

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

PubMed Central

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

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

2010-01-01

118

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

PubMed

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

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

2013-07-27

119

Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats.  

PubMed

CGRP and substance P (SP) are produced in dorsal root ganglia (DRG) sensory neurons and modulate vascular tone. Sympathetic and sensory nerves compete for NGF, a potent stimulator of CGRP and SP, and it has been suggested that sympathetic hyperinnervation in spontaneously hypertensive rats may reduce the availability of NGF to sensory nerves, thus reducing CGRP and SP. The purpose of this study was to determine whether destruction of peripheral sympathetic nerves in normal rats would increase the availability of NGF for sensory neurons and enhance expression of CGRP and SP. Sympathectomy was produced in rats by guanethidine sulfate administration. Control rats received saline. Sympathectomized rats displayed reductions in blood pressure (BP) and atria norepinephrine levels, whereas NGF levels in the DRG, spleen, and ventricles were increased. Sympathectomy also enhanced CGRP and SP mRNA and peptide content in DRG. Administration of CGRP and SP receptor antagonists increased the BP in sympathectomized rats but not in the controls. Thus sympathectomy enhances sensory neuron CGRP and SP expression that contributes to the BP reduction. PMID:15879482

Supowit, S C; Ethridge, R T; Zhao, H; Katki, K A; Dipette, D J

2005-05-06

120

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

PubMed Central

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.

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

2010-01-01

121

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

PubMed Central

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

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

2012-01-01

122

Trans-11 vaccenic acid reduces hepatic lipogenesis and chylomicron secretion in JCR:LA-cp rats.  

PubMed

Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid concentrations, as well as the serum haptoglobin concentration, were all lower in obese rats fed the VA diet compared with obese controls (P < 0.05). In addition, there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area under the curve (P < 0.05) for VA-treated obese rats compared with obese controls. The hepatic TG concentration and the relative abundance of fatty acid synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA-treated group compared with obese controls. Following acute gastrointestinal infusion of a VA-triolein emulsion in obese rats that had been fed the control diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by 30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In conclusion, chronic VA supplementation significantly improved dyslipidemia in both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways. PMID:19759243

Wang, Ye; Jacome-Sosa, M Miriam; Ruth, Megan R; Goruk, Sue D; Reaney, Martin J; Glimm, David R; Wright, David C; Vine, Donna F; Field, Catherine J; Proctor, Spencer D

2009-09-16

123

Supplementation of fenugreek leaves reduces oxidative stress in streptozotocin-induced diabetic rats.  

PubMed

Trigonella foenum-graecum, commonly known as fenugreek, is a traditional medicinal plant of the Leguminoseae family in India. The antioxidant effect of fenugreek leaves was evaluated in the streptozotocin-induced diabetic rat model. The antioxidant effect was evaluated by estimating thiobarbituric acid-reactive substances and reduced glutathione and measuring the activities of catalase and superoxide dismutase in liver, heart, and kidney in diabetic rats. Fenugreek leaf powder supplementation significantly lowered lipid peroxidation and significantly increased the antioxidant system in diabetic rats. The effect at a dose of 1 g/kg of body weight of fenugreek leaf powder was similar to that of glibenclamide. Insulin restores all the parameters to near normal values. Thus, fenugreek leaf powder reduces oxidative stress in experimental diabetes. PMID:16176151

Annida, B; Stanely Mainzen Prince, P

2005-01-01

124

Effect of forelimb lameness on hoof kinematics of horses at a trot.  

PubMed

Objective-To determine kinematic changes to the hoof of horses at a trot after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness values after perineural anesthesia. Animals-6 clinically normal Quarter Horses. Procedures-For each horse, a sole-pressure model was used to induce 3 grades (grades 1, 2, and 3) of lameness in the right forelimb, after which perineural anesthesia was administered to alleviate lameness. Optical kinematics were obtained for both forelimbs with the horse trotting before (baseline) and after induction of each grade of lameness and after perineural anesthesia. Hoof events were identified with linear acceleration profiles, and each stride was divided into hoof-contact, break-over, initial-swing, terminal-swing, and total-swing segments. For each segment, kinematic variables were compared within and between limbs by use of mixed repeated-measures ANOVA. Results-During hoof-contact, the left (nonlame) forelimb hoof had greater heel-down orientation than did the right (lame) forelimb hoof, and during break-over, the nonlame hoof went through a larger range of motion than did the lame hoof. Maximum cranial acceleration during break-over for the lame hoof was greater, compared with that at baseline or for the nonlame hoof. Following perineural anesthesia, the sagittal plane orientation of the hoof during hoof-contact did not vary between the lame and nonlame limbs; however, interlimb differences in maximum cranial acceleration and angular range of motion during break-over remained. Conclusions and Clinical Relevance-Results suggested that hoof kinematics may be useful for detection of unilateral, weight-bearing forelimb lameness in horses that are trotting. PMID:23977890

Moorman, Valerie J; Reiser, Raoul F; Peterson, Michael L; McIlwraith, C Wayne; Kawcak, Chris E

2013-09-01

125

Effect of forelimb lameness on hoof kinematics of horses at a walk.  

PubMed

Objective-To determine kinematic changes to the hoof of horses at a walk after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness (baseline) values after perineural anesthesia. Animals-6 clinically normal Quarter Horses. Procedures-For each horse, a sole-pressure model was used to induce 3 grades of lameness in the right forelimb, after which perineural anesthesia was administered to eliminate lameness. Optical kinematics were obtained for both forelimbs with the horse walking before (baseline) and after induction of each grade of lameness and after perineural anesthesia. Linear acceleration profiles were used to identify hoof events, and each stride was divided into hoof-contact, break-over, initial-swing, terminal-swing, and total-swing segments. Kinematic variables were compared within and between limbs for each segment by use of mixed repeated-measures ANOVA. Results-During the hoof-contact and terminal-swing segments, the hoof of the left (nonlame) forelimb had greater sagittal-plane orientation than did the hoof of the right (lame) forelimb. For the lame limb following lameness induction, the break-over duration and maximum cranial acceleration were increased from baseline. After perineural anesthesia, break-over duration for the lame limb returned to a value similar to that at baseline, and orientation of the hoof during the terminal-swing segment did not differ between the lame and nonlame limbs. Conclusions and Clinical Relevance-Subclinical unilateral forelimb lameness resulted in significant alterations to hoof kinematics in horses that are walking, and the use of hoof kinematics may be beneficial for the detection of subclinical lameness in horses. PMID:23977891

Moorman, Valerie J; Reiser, Raoul F; Peterson, Michael L; McIlwraith, C Wayne; Kawcak, Chris E

2013-09-01

126

ANG II reduces net acid secretion in rat outer medullary collecting duct.  

PubMed

In rat outer medullary collecting duct (OMCD), the mechanism(s) and regulation of H+ secretion are not understood fully. The effect of changes in acid-base balance and the renin-angiotensin system on net H+ secretion was explored. Rats received NaCl, NaHCO3, NH4Cl, or nothing in their drinking water for 7 days. Total ammonia and total CO2 (JtCO2) fluxes were measured in OMCD tubules perfused in vitro from rats in each treatment group. JtCO2 was reduced in tubules from rats drinking NH4Cl relative to those drinking NaHCO3. Because NH4Cl intake increases plasma renin and aldosterone, we asked if upregulation of the renin-angiotensin system reduces net H+ secretion. Deoxycorticosterone pivalate administered in vivo did not affect JtCO2. However, ANG II given in vivo at 0.1 ng/min reduced JtCO2 by 35%. To determine if ANG II has a direct effect on acid secretion, JtCO2 was measured with ANG II applied in vitro. ANG II (10-8 M) present in the bath solution reduced JtCO2 by 35%. This ANG II effect was not observed in the presence of the AT1 receptor blocker candesartan. In conclusion, in rat OMCD, JtCO2 is paradoxically reduced with NH4Cl ingestion. Increased circulating ANG II, as occurs during metabolic acidosis, reduces JtCO2. PMID:12851254

Wall, Susan M; Fischer, Michael P; Glapion, Dawn M; De La Calzada, Mae

2003-07-08

127

Utilization of the Denny-Brown collection: Differential recovery of forelimb and hind limb stepping after extensive unilateral cerebral lesions  

Microsoft Academic Search

The Denny-Brown collection of primate lesion material was used to test the hypothesis that there is a difference in the rate of forelimb and hind limb recovery of locomotor movements after major unilateral cerebral ablation (pre\\/postcentral gyrus, decortication or hemispherectomy). The results indicate that, following major cerebral injury, hind limb recovery precedes that of the forelimb in adolescent and adult

Joel A. Vilensky; Sid Gilman; Elizabeth A. Dunn; W. Jeffrey Wilson

1997-01-01

128

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

129

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

Microsoft Academic Search

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

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

2010-01-01

130

Free, Long-Chain, Polyunsaturated Fatty Acids Reduce Membrane Electrical Excitability in Neonatal Rat Cardiac Myocytes  

Microsoft Academic Search

Because previous studies showed that polyunsaturated fatty acids can reduce the contraction rate of spontaneously beating heart cells and have antiarrhythmic effects, we examined the effects of the fatty acids on the electrophysiology of the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of cardiomyocytes to 10 muM eicosapentaenoic acid for 2-5 min markedly increased the strength of the

Jing X. Kang; Yong-Fu Xiao; Alexander Leaf

1995-01-01

131

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

Microsoft Academic Search

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

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

1999-01-01

132

Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats  

Microsoft Academic Search

BACKGROUND: Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. METHODS: Sixty-four rats were randomized

Matteo Runfola; Simone Rossi; Simona Panunzi; Pier Luigi Spada; Daniele Gui

2003-01-01

133

Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in diabetic rats  

Microsoft Academic Search

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

Barry M Wilkes; Randy Kaplan; Peter F Mento; Hagop S Aynedjian; Carolyn M Macica; Detlef Schlondorff; Norman Bank

1992-01-01

134

Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion  

Microsoft Academic Search

Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic\\/cataplerotic\\u000a pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic\\u000a enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic\\/cataplerotic\\u000a enzymes content. Male Wistar rats were randomly assigned to one

Claudio C. ZoppiVivian; Vivian C. Calegari; Leonardo R. Silveira; Everardo M. Carneiro; Antonio C. Boschero

135

Central regulation of motor cortex neuronal responses to forelimb nerve inputs during precision walking in the cat  

PubMed Central

The responses of neurones in forelimb motor cortex to impulse volleys evoked by single pulse electrical stimulation (at 1.5 or 2 times the threshold for most excitable nerve fibres) of the superficial radial (SR) and ulnar (UL) nerves of the contralateral forelimb were studied in awake cats both resting quietly and walking on a horizontal ladder. Nerve volley amplitude was monitored by recording the compound action potential elicited by the stimulus. In the resting animal 34/82 (41 %) cells yielded statistically significant responses to SR stimulation, and 20/72 (28 %) responded to UL stimulation. Some responses were confined to or began with an increase in firing probability (‘excitatory’ responses) and others with a decrease in firing (‘inhibitory’ responses), typically including a brief interruption of the spike train (zero rate). Cells responding to both nerves usually yielded responses similar in type. Most (78 %) response onset latencies were less than 30 ms. Responses involved the addition or subtraction of from 3.4 to 0.1 impulses stimulus?1 (most < 1 impulse stimulus?1). The distribution of response sizes was continuous down to the smallest values, i.e. there was no ‘gap’ which would represent a clear separation into ‘responsive’ and ‘unresponsive’ categories. Responses were commonest in the lateral part of the pericruciate cortex, and commoner among pyramidal tract neurones (PTNs) than non-PTNs. During ladder walking most cells generated a rhythmic step-related discharge; in assessing the size of responses to nerve stimulation (20 studied, from 13 cells) this activity was first subtracted. Response onset latencies (90 % < 30 ms) and durations showed little or no change. Although most cells were overall more active than during rest both ‘excitatory’ and ‘inhibitory’ responses in both PTNs and non-PTNs were often markedly reduced in large parts of the step cycle; over some (usually brief) parts responses approached or exceeded their size during rest, i.e. response size was step phase dependent. Such variations occurred without parallel change in the nerve compound action potential, nor were they correlated with the level of background firing at the time that the response was evoked. When responses to both nerves were studied in the same neurone they differed in their patterns of phase dependence. The findings are interpreted as evidence for central mechanisms that, during ‘skilled’, cortically controlled walking, powerfully regulate the excitability of the somatic afferent paths from forelimb mechanoreceptors (including low threshold cutaneous receptors) to motor cortex. Retention (or enhancement) of responsiveness often occurred (especially for ulnar nerve) around footfall, perhaps reflecting a behavioural requirement for sensory input signalling the quality of the contact established with the restricted surface available for support.

Marple-Horvat, D E; Armstrong, D M

1999-01-01

136

Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury.  

PubMed

We previously showed that electrical stimulation of motor cortex (M1) after unilateral pyramidotomy in the rat increased corticospinal tract (CST) axon length, strengthened spinal connections, and restored forelimb function. Here, we tested: (i) if M1 stimulation only increases spinal axon length or if it also promotes connections to brain stem forelimb control centers, especially magnocellular red nucleus; and (ii) if stimulation-induced increase in axon length depends on whether pyramidotomy denervated the structure. After unilateral pyramidotomy, we electrically stimulated the forelimb area of intact M1, to activate the intact CST and other corticofugal pathways, for 10 days. We anterogradely labeled stimulated M1 and measured axon length using stereology. Stimulation increased axon length in both the spinal cord and magnocellular red nucleus, even though the spinal cord is denervated by pyramidotomy and the red nucleus is not. Stimulation also promoted outgrowth in the cuneate and parvocellular red nuclei. In the spinal cord, electrical stimulation caused increased axon length ipsilateral, but not contralateral, to stimulation. Thus, stimulation promoted outgrowth preferentially to the sparsely corticospinal-innervated and impaired side. Outgrowth resulted in greater axon density in the ipsilateral dorsal horn and intermediate zone, resembling the contralateral termination pattern. Importantly, as in spinal cord, increase in axon length in brain stem also was preferentially directed towards areas less densely innervated by the stimulated system. Thus, M1 electrical stimulation promotes increases in corticofugal axon length to multiple M1 targets. We propose the axon length change was driven by competition into an adaptive pattern resembling lost connections. PMID:23360401

Carmel, Jason B; Kimura, Hiroki; Berrol, Lauren J; Martin, John H

2013-01-29

137

Weight loss and melatonin reduce obesity-induced oxidative damage in rat testis.  

PubMed

Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1), obesity group (Group 2), obesity + MLT group (Group 3), and weight loss group (Group 4). Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5?cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P < 0.05). Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P < 0.05). There was no significant difference between groups in terms of mean Johnsen score (P = 0.727). Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes. PMID:24089609

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

2013-09-08

138

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

PubMed Central

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

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

2013-01-01

139

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

PubMed Central

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

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

1985-01-01

140

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

PubMed

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

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

2012-11-08

141

Terutroban, a TP-receptor antagonist, reduces portal pressure in cirrhotic rats.  

PubMed

Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2 /prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride (CCl4 ) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction), and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4 -cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4 -cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (?-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway. Conclusion: Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis. This effect is due to decreased hepatic resistance, which in CCl4 -cirrhotic rats was linked to decreased hepatic fibrosis, but not in BDL rats, in which the main mediator appeared to be an enhanced eNOS-dependent vasodilatation, which was not liver-selective, as it was associated with decreased arterial pressure. The potential use of terutroban for portal hypertension requires further investigation. (Hepatology 2013;58:1424-1435). PMID:23703868

Rosado, Eugenio; Rodríguez-Vilarrupla, Aina; Gracia-Sancho, Jorge; Tripathi, Dinesh; García-Calderó, Héctor; Bosch, Jaume; García-Pagán, Juan Carlos

2013-08-07

142

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats  

Microsoft Academic Search

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric\\u000a mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly\\u000a reduced portal pressures (24±1 vs 32±1 cm saline), macroscopic mucosal damage (24 ±1 vs 39±4% of mucosa), and histologic deep\\u000a necrosis (36±2 vs 61±4% of mucosal

H. Sankary; I. J. Sarfeh; A. Tarnawski; R. Maeda; K. J. Ivey; G. R. Mason

1986-01-01

143

Neuroaminidase Reduces Interictal Spikes in a Rat Temporal Lobe Epilepsy Model  

PubMed Central

Summary Interictal spikes have been implicated in epileptogenesis and cognitive dysfunction in epilepsy. Unfortunately, antiepileptic drugs have shown poor efficacy in suppressing interictal discharges and novel therapies are needed. Surface charge on neuronal membranes provides a novel target for abolishing interictal spikes. This property can be modulated through the use of neuraminidase, an enzyme which decreases the amount of negatively charged sialic acid. In the present report we determined whether applying neuraminidase to brains of rats with a prior history of status epilepticus would reduce number of interictal discharges. Following pilocarpine-induced status epilepticus rats received intrahippocampal injections of neuraminidase, which significantly decreased the number of interictal spikes recorded in the CA1 region. This study provides evidence that sialic acid degradation can reduce the number of interictal spikes. Furthermore, the results suggest that modifying surface charge created by negatively charged sialic acid may provide new opportunities for reducing aberrant epileptiform events in epilepsy.

Isaev, Dmytro; Zhao, Qian; Kleen, Jonathan K.; Lenck-Santini, Pierre Pascal; Adstamongkonkul, Dusit; Isaeva, Elena; Holmes, Gregory L.

2012-01-01

144

Chronic Alternate Day Fasting Results in Reduced Diastolic Compliance and Diminished Systolic Reserve in Rats  

PubMed Central

Background Based on animal experiments and limited data from few human trials, alternate day fasting (ADF) resulted in weight loss; prolonged life; reduced metabolic risk factors for diabetes and cardiovascular diseases; and reduced prevalence of age-related diseases. The present study is the first comprehensive examination of the long-term effects of ADF on general cardiovascular fitness in rats. Methods and Results Four months old male Sprague-Dawley rats were started on ADF or continued on ad libitum diets and followed for 6 months with serial echocardiography. A comprehensive hemodynamic evaluation including a combined dobutamine - volume stress test was performed at the end of the study, and hearts were harvested for histological assessment. The six-month long ADF diet resulted in a 9% reduction (p<0.01) of cardiomyocyte diameter and 3 fold increase in interstitial myocardial fibrosis. Left ventricular chamber size was not affected by ADF and ejection fraction was not reduced, but left atrial diameter was increased 16%, and the E/A in Doppler-measured mitral flow was reduced (p<0.01). Pressure-volume loop analyses revealed a “stiff” heart during diastole in ADF rats, while combined dobutamine and volume loading showed a significant reduction in LV diastolic compliance and a lack of increase in systolic pump function, indicating a diminished cardiac reserve. Conclusion Chronic ADF in rats results in development of diastolic dysfunction with diminished cardiac reserve. ADF is a novel and unique experimental model of diet-induced diastolic dysfunction. The deleterious effect of ADF in rats suggests that additional studies of ADF effects on cardiovascular functions in humans are warranted.

Ahmet, Ismayil; Wan, Ruiqian; Mattson, Mark P; Lakatta, Edward G.; Talan, Mark I.

2010-01-01

145

Anti-convulsant effects by reduced glutathione and related aminoacids in rats treated with isoniazid.  

PubMed

Rats were treated with different doses of isoniazid (INH) causing convulsions. Lethal dose (DL50) and effective convulsant dose (ED50) were calculated. Reduced glutathione (GSH) and related aminoacids were administered to rats receiving INH: the latency and duration of convulsions were recorded; cerebral gamma-aminobutyric acid (GABA) concentrations were determined in rats receiving INH and an association of GSH and INH. GSH and its related aminoacids as cysteine and glycine greatly decreased the duration of INH-induced seizures, while glutamic acid did not protect against convulsions caused by INH. Furthermore, INH causes a decrease in cerebral GABA levels to about half and GSH repeated pretreatment did, however, not prevent the INH induced decline of GABA content: hence, the anticonvulsant effect of GSH can not be ascribed to the restoration of normal levels of anti-epilectically acting GABA, but can be attributed to cysteine and glycine, aminoacids linked to GSH. PMID:2892286

Pinelli, A; Trivulzio, S; Colombo-Zefinetti, G; Tofanetti, O

1988-01-01

146

Ascending long spinal actions on forelimb motoneurons in the acute spinal cat  

Microsoft Academic Search

Ascending long spinal reflex system were investigated by means of monosynaptic reflex testing in the acutely spinalized unanesthetized cat.1.Hindlimb nerve stimulation gave bilateral facilitatory effects on the motoneuron pools of pectoralis major and physiological flexors of the forelimb such as biceps brachii, extensor carpi radialis, extensor digitorum communis, but elicited depressive effects on the physiological extensors such as triceps brachii,

A. Matsumoto; M. Aoki; S. Mori

1976-01-01

147

Axonal projection of descending pathways responsible for eliciting forelimb stepping into the cat cervical spinal cord  

Microsoft Academic Search

The descending pathways responsible for eliciting forelimb stepping are located in the lateral funiculus (Yamaguchi 1986). In order to determine into which spinal segments the descending pathways project and to know the projections and functions of the other descending system, the ventral funicular pathways, we placed various lesions in the cervical spinal cord of decerebrate cats with the lower thoracic

M. Hishinuma; T. Yamaguchi

1990-01-01

148

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

Microsoft Academic Search

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

Virginia Abdala; Adriana S. Manzano; Anthony Herrel

2008-01-01

149

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

Microsoft Academic Search

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

N. Stephens; N. Holder

1985-01-01

150

Forelimb posture in dinosaurs and the evolution of the avian flapping flight-stroke.  

PubMed

Ontogenetic and behavioral studies using birds currently do not document the early evolution of flight because birds (including juveniles) used in such studies employ forelimb oscillation frequencies over 10 Hz, forelimb stroke-angles in excess of 130 degrees , and possess uniquely avian flight musculatures. Living birds are an advanced morphological stage in the development of flapping flight. To gain insight into the early stages of flight evolution (i.e., prebird), in the absence of a living analogue, a new approach using Strouhal number was used. Strouhal number is a nondimensional number that describes the relationship between wing-stroke amplitude (A), wing-beat frequency (f), and flight speed (U). Calculations indicated that even moderate wing movements are enough to generate rudimentary thrust and that a propulsive flapping flight-stroke could have evolved via gradual incremental changes in wing movement and wing morphology. More fundamental to the origin of the avian flapping flight-stroke is the question of how a symmetrical forelimb posture-required for gliding and flapping flight-evolved from an alternating forelimb motion, evident in all extant bipeds when running except birds. PMID:19154383

Nudds, Robert L; Dyke, Gareth J

2009-01-14

151

The evolution of manus shape in sauropod dinosaurs: implications for functional morphology, forelimb orientation, and phylogeny  

Microsoft Academic Search

Sauropods have a unique digitigrade and semi-tubular manus whose shape has been used as a synapomorphy that unites most sauropod taxa. The vertical orientation and semi-tubular arrangement of the metacarpale suggest the sauropod manus improved the mechanical ability of the forelimb to support great weight. However, the evolutionary mechanism responsible for modifying the relatively flat metacarpus of basal saurischians into

Matthew F. Bonnan

2003-01-01

152

Gross anatomy of the forelimb and shoulder girdle of the Galago senegalensis  

Microsoft Academic Search

The gross anatomy of the forelimb of theGalago senegalensis is described. The skeletal, muscular, nervous, and vascular systems are illustrated. TheGalago senegalensis is compared to theTarsius and other selected primates. Also examined in the study are muscle attachments and selected upper limb indices derived from\\u000a measurements of bone dimensions.

James L. Stevens; Deborah M. Meyer; V. REGGIE EDGERTON

1977-01-01

153

Multicentric schwannomas causing chronic ruminal tympany and forelimb paresis in a Holstein cow.  

PubMed

A nine-year-old Holstein cow that developed recurrent ruminal tympany and an abnormal forelimb gait and posture ultimately became recumbent and unable to rise, and was euthanased. A postmortem examination demonstrated numerous schwannomas affecting peripheral nerves and several thoracic and abdominal viscera. PMID:9172298

Peek, S F; Del Piero, F; Rebhun, W C; Adamus, C

1997-05-10

154

Hox genes regulate the onset of Tbx5 expression in the forelimb  

PubMed Central

Tbx4 and Tbx5 are two closely related T-box genes that encode transcription factors expressed in the prospective hindlimb and forelimb territories, respectively, of all jawed vertebrates. Despite their striking limb type-restricted expression pattern, we have shown that these genes do not participate in the acquisition of limb type-specific morphologies. Instead, Tbx4 and Tbx5 play similar roles in the initiation of hindlimb and forelimb outgrowth, respectively. We hypothesized that different combinations of Hox proteins expressed in different rostral and caudal domains of the lateral plate mesoderm, where limb induction occurs, might be involved in regulating the limb type-restricted expression of Tbx4 and Tbx5 and in the later determination of limb type-specific morphologies. Here, we identify the minimal regulatory element sufficient for the earliest forelimb-restricted expression of the mouse Tbx5 gene and show that this sequence is Hox responsive. Our results support a mechanism in which Hox genes act upstream of Tbx5 to control the axial position of forelimb formation.

Minguillon, Carolina; Nishimoto, Satoko; Wood, Sophie; Vendrell, Elisenda; Gibson-Brown, Jeremy J.; Logan, Malcolm P. O.

2012-01-01

155

Copper deficiency shifts energy substrate utilization from carbohydrate to fat and reduces fat mass in rats.  

PubMed

The influence of copper deficiency on energy metabolism and body composition was examined in rats. Weanling male Sprague-Dawley rats were assigned to two dietary treatments: copper-adequate (102.2 mumol/kg) and copper-deficient (9.0 mumol/kg). After 4 wk of treatment, rats were individually housed in metabolic cages within indirect calorimetry units for measurements of respiratory quotient to determine substrate utilization. Body composition was measured by total body electrical conductivity. Net energetic efficiency and fasting heat production were determined from regression analysis of metabolizable energy intake and energy retention (metabolizable energy intake-heat production). Rats were given free access to their respective diets for almost the entire study but were restricted to 70% of normal energy intake for 2 d to provide a range of energy intake required for the regression analysis. Energetic evaluations were determined for 12 d at normal intake and 2 d at a modest restriction (30%). Copper deficiency reduced the respiratory quotient values (0.85 to 0.80), carbohydrate utilization (7.9 to 5.2 g/d), energy retention [8.4 to -66.9 kJ/kg0.75.d)] and energy efficiency (97.8 to 87.7%). However, daily metabolizable energy intake and absolute fasting heat production were not altered. Reductions in final body weights (289 to 263 g), absolute fat mass (65.7 to 51.5 g) and proportion of body fat (22.7 to 19.6 g/100 g) were observed in copper-deficient rats compared with controls when all indirect calorimetry measurements were completed after 7 wk of treatment. Thus, copper deficiency increased utilization of fat as substrate for energy and reduced body fat mass in rats. PMID:8089733

Hoogeveen, R C; Reaves, S K; Reid, P M; Reid, B L; Lei, K Y

1994-09-01

156

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

PubMed Central

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

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

2001-01-01

157

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.

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

2010-01-01

158

COMBINED ALISKIREN AND AMLODIPINE REDUCE ALBUMINURIA VIA REDUCTION IN RENAL INFLAMMATION IN DIABETIC RATS  

PubMed Central

SUMMARY We hypothesized that compared to hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of BP changes. We studied normal and streptozotocin induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ or AMLO individually and combined and evaluated effects of treatments on BP, urine albumin to creatinine ratio (UACR), renal interstitial fluid (RIF) levels of angiotensin II (Ang II), tumor necrosis factor-alpha (TNF?) and interleukin-6 (IL-6), and renal expression of TNF?, IL-6, transforming growth factor-beta1 (TGF-?1) and nuclear factor-kappa B (NF-?B). There were no differences in BP between treatments. Only ALISK and its combinations reduced RIF Ang II. UACR increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence UACR. RIF TNF? and IL-6, and the renal expression of TNF?, IL-6, TGF-?1 and NF-?B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes.

Matavelli, Luis C.; Huang, Jiqian; Siragy, Helmy M.

2011-01-01

159

Combined aliskiren and amlodipine reduce albuminuria via reduction in renal inflammation in diabetic rats.  

PubMed

We hypothesized that compared with hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of blood pressure (BP) changes. We studied normal and streptozotocin-induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ, or AMLO individually and combined and evaluated the effects of treatments on BP, urine albumin to creatinine ratio, renal interstitial fluid levels of angiotensin II, tumor necrosis factor alpha (TNF-?), and interleukin 6 (IL-6) and renal expression of TNF-?, IL-6, transforming growth factor beta 1, and nuclear factor kappa B. There were no differences in BP between treatments. Only ALISK and its combinations reduced renal interstitial fluid angiotensin II. Urine albumin to creatinine ratio increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence urine albumin to creatinine ratio. Renal interstitial fluid TNF-? and IL-6, and the renal expression of TNF-?, IL-6, transforming growth factor beta 1, and nuclear factor kappa B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes. PMID:22075749

Matavelli, Luis C; Huang, Jiqian; Siragy, Helmy M

2012-03-01

160

Green tea polyphenols reduce body weight in rats by modulating obesity-related genes.  

PubMed

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n?=?12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1?, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1? and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

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

2012-06-08

161

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

PubMed Central

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

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

2009-01-01

162

Acute ethanol administration reduces the cognitive deficits associated with traumatic brain injury in rats.  

PubMed

The present study was designed to determine whether a low dose of acute ethanol administration could attenuate cognitive deficits associated with traumatic brain injury. Adult male rats received oral administration of ethanol or drinking water 2 h prior to surgery to produce a blood ethanol concentration of 100 mg% and then received bilateral contusion injuries of the medial prefrontal cortex. Seven days after surgery, the rats began 10 days of testing for acquisition of spatial localization in the Morris water maze where they were required to find a hidden platform to escape from the water. The results indicate that the rats given ethanol at the time of injury later spent significantly less time searching for the hidden platform than their water-treated counterparts. On a memory probe test given on the final day of testing, in which the platform was removed from the pool, rats given the ethanol spent more time in the area where the platform had been located indicating that they learned its location better than the lesion/water controls. In addition, acute ethanol treatment reduced some of the histopathology that typically occurs following severe contusion of the medial frontal cortex but did not attenuate post-traumatic formation of edema. These results indicate that acute ethanol intoxication can reduce the severity of cognitive impairments caused by contusive traumatic brain injury and support the contention that there is a dose-response relationship of acute ethanol intoxication in the setting of traumatic brain injury. PMID:9512086

Janis, L S; Hoane, M R; Conde, D; Fulop, Z; Stein, D G

1998-02-01

163

Palmatine from Coptidis rhizoma reduces ischemia-reperfusion-mediated acute myocardial injury in the rat.  

PubMed

The aim of the present study was to evaluate the protective effect of palmatine, one of active ingredients of Coptidis rhizoma, against myocardial ischemia-reperfusion (I/R) injury is due to its antioxidant and anti-inflammatory action. Adult male rats were subjected to 30 min of ischemia and 6 or 24h of reperfusion. Rats were randomized to receive vehicle or palmatine 1h before reperfusion. Infarct size, myocardial function, and the antioxidant enzyme activity, such as malonaldehyde (MDA), lactate dehydrogenase (LDH), creatine phosphokinase (CK), superoxide dismutase (SOD) and catalase (CAT) were measured. Palmatine significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (+/-dp/dt) of left ventricular pressure and decreased infarct size by 50% (P<0.01 versus vehicle). As expected, palmatine markedly inhibited the increase of LDH, CK, and MDA contents in I/R rat serum, and it also significantly inhibited the decline of the activity of SOD and CAT in I/R cardiac tissues. In addition, COX-2 and iNOS expression in I/R myocardium was significantly reduced. Interestingly, palmatine increased heme oxygenase (HO)-1 induction in human aortic endothelial cells. We concluded that palmatine protects hearts from I/R injury in rats possibly by reducing oxidative stress and modulating inflammatory mediators. PMID:19497345

Kim, Young Min; Ha, Yu Mi; Jin, Yong Chun; Shi, Lian Yu; Lee, Yong Soo; Kim, Hye Jung; Seo, Han Geuk; Choi, Jae Soo; Kim, Yeong Shik; Kang, Sam Sik; Lee, Jae Heun; Chang, Ki Churl

2009-06-02

164

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.

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

2010-01-01

165

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.

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

2012-01-01

166

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

Microsoft Academic Search

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

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

2001-01-01

167

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

Microsoft Academic Search

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

Francesco Leri; Lindsay H. Burns

2005-01-01

168

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

Microsoft Academic Search

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

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

2010-01-01

169

Cyclic adenosine monophosphate-phosphodiesterase inhibitors reduce skeletal muscle protein catabolism in septic rats.  

PubMed

We have previously shown that catecholamines exert an inhibitory effect on muscle protein degradation through a pathway involving the cyclic adenosine monophosphate (cAMP) cascade in normal rats. In the present work, we investigated in vivo and in vitro effects of cAMP-phosphodiesterase inhibitors on protein metabolism in skeletal muscle from rats submitted to a model of acute sepsis. The in vivo muscle protein metabolism was evaluated indirectly by measurements of the tyrosine interstitial concentration using microdialysis. Muscle blood flow (MBF) was monitored by ethanol perfusion technique. Sepsis was induced by cecal ligation and puncture and resulted in lactate acidosis, hypotension, and reduction in MBF (-30%; P < 0.05). Three-hour septic rats showed an increase in muscle interstitial tyrosine concentration (approximately 150%), in arterial plasma tyrosine levels (approximately 50%), and in interstitial-arterial tyrosine concentration difference (approximately 200%; P < 0.05). Pentoxifylline (50 mg/kg of body weight, i.v.) infusion during 1 h after cecal ligation and puncture prevented the tumor necrosis factor alpha increase and significantly reduced by 50% (P < 0.05) the interstitial-arterial tyrosine difference concentration. In situ perfusion with isobutylmethylxanthine (IBMX; 10(-3) M) reduced by 40% (P < 0.05) the muscle interstitial tyrosine in both sham-operated and septic rats. Neither pentoxifylline nor IBMX altered MBF. The addition of IBMX (10(-3) M) to the incubation medium increased (P < 0.05) muscle cAMP levels and reduced proteolysis in both groups. The in vitro addition of H89, a protein kinase A inhibitor, completely blocked the antiproteolytic effect of IBMX. The data show that activation of cAMP-dependent pathways and protein kinase A reduces muscle protein catabolism during basal and septic state. PMID:17505310

Lira, Eduardo Carvalho; Graca, Flávia Aparecida; Goncalves, Dawit Albieiro P; Zanon, Neusa M; Baviera, Amanda Martins; Strindberg, Lena; Lönnroth, Peter; Migliorini, Renato Hélios; Kettelhut, Isis C; Navegantes, Luiz Carlos C

2007-06-01

170

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

Microsoft Academic Search

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

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

2011-01-01

171

Diabetes Reduces Growth and Body Composition More in Male Than in Female Rats  

Microsoft Academic Search

Food restriction and\\/or starvation has a consistently greater and more permanent effect on physical growth in males than in females. Because diabetes may be viewed as being analogous to starvation, we tested the hypothesis that diabetes would reduce growth more in male than in female rats. Diabetes was induced with streptozotocin (65–125 mg\\/kg IP) at 3 weeks of age in

RONALD N CORTRIGHT; HEIDI L COLLINS; MARGARET P CHANDLER; PETER W. R LEMON; STEPHEN E DiCARLO

1997-01-01

172

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.

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

2011-01-01

173

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

PubMed

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

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

2013-08-18

174

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

PubMed

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

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

2013-03-28

175

Motion picture analysis of rat mating behavior  

Microsoft Academic Search

Studied the interaction and coordination of male and female rats during mounting and lordosis, using 12 primiparous female and 4 male Sprague-Dawley rats. Head, body, and limb movements of the female are described in relation to forelimb and pelvic movements of the male during mounting. Data show that (a) mounts with ejaculation were longer than mounts without ejaculation; (b) during

Carol Diakow

1975-01-01

176

A-ring reduced derivatives of two synthetic progestins induce anxiolytic effects in ovariectomized rats  

Microsoft Academic Search

The putative anxiolytic action of the synthetic progestins, norethisterone (NET), levonorgestrel (LNG) and their respective 5?-reduced metabolites, (5?-NET), (3?,5?-NET), (3?,5?-NET), (5?-LNG), (3?,5?-LNG) and (3?,5?-LNG), were studied in the burying behavior paradigm. From these compounds only 3?,5?-NET and 3?,5?-LNG reduced burying behavior without modifying other parameters. Burying behavior latency was prolonged after administration of the highest dose (1.0 mg\\/rat) of NET

O Picazo; A Fernández-Guasti; A. E Lemus; G. A Garc??a

1998-01-01

177

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

PubMed

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

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

1999-06-01

178

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

PubMed Central

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

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

2011-01-01

179

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

PubMed

Rats were trained to self-administer intravenously-delivered cocaine. Four lever-press responses resulted in a cocaine infusion (0.2 mg/kg) during daily 24-h sessions. The rats were also trained to obtain water from tongue-operated solenoid-driven drinking spouts. Ground food and water from a standard drinking bottle were also available. When cocaine injections reached stable levels, L-tryptophan was mixed with the rats' food for 5 days. Three concentrations of L-tryptophan (2, 4, and 8%) were tested in different groups of five rats each. Three other groups of five rats each received the same L-tryptophan treatments; however, in these rats saline was substituted for cocaine and a sweet drinking solution consisting of glucose and saccharin (G + S) replaced water in the automatic drinking device. Two other groups consisting of five rats each self-administered a higher (0.4 mg/kg) or lower (0.1 mg/kg) unit dose of cocaine and food adulterated with 4% tryptophan. At the two higher concentrations L-tryptophan reduced cocaine infusions by at least 50% during the 5 days of treatment, and cocaine infusions returned to baseline levels within 48 h after the regular diet was restored. Responding reinforced by the G + S solution was not altered by any of the L-tryptophan concentrations. Food intake was substantially lowered by the 8% L-tryptophan concentration; however, water intake, responding on an inactive lever, and the number of saline infusions were not affected by addition of L-tryptophan to the food. L-Tryptophan had the same magnitude of effect on self-administration of the 0.1 and 0.2 mg/kg unit doses of cocaine, but behavior maintained by the highest cocaine dose (0.4 mg/kg) was resistant to the effect of L-tryptophan. The results of this experiment indicate that L-tryptophan reduces behavior reinforced by IV cocaine infusions. PMID:2315426

Carroll, M E; Lac, S T; Asencio, M; Kragh, R

1990-01-01

180

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

181

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

PubMed

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

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

2010-04-01

182

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

PubMed

Stressors, during early life or adulthood, can alter steroid-sensitive behaviors, such as exploration, anxiety, and/or cognitive processes. We investigated if exposure to acute stressors in adulthood may alter behavioral and neuroendocrine responses of male rats that were exposed to gestational stress or not. We hypothesized that rats exposed to gestational and acute stress may show behavioral inhibition, increased corticosterone, and altered androgen levels in the hippocampus. Subjects were adult, male offspring of rat dams that were restrained daily on gestational days 14-20, or did not experience this manipulation. Immediately before testing, rats were restraint stressed for 20 min or not. During week 1, rats were tested in a battery of tasks, including the open field, elevated plus maze, social interaction, tailflick, pawlick, and defensive burying tasks. During week 2, rats were trained and tested 24 h later in the inhibitory avoidance task. Plasma corticosterone and androgen levels, and hippocampal androgen levels, were measured in all subjects. Gestational and acute restraint stress increased plasma levels of corticosterone, and reduced levels of testosterone's 5?-reduced metabolites, dihydrotestosterone (DHT) and 3?-androstanediol (3?-diol), but not the aromatized metabolite, estradiol (E(2)), in plasma or the hippocampus. Gestational and acute restraint stress reduced central entries made in the open field, and latencies to enter the shock-associated side of the inhibitory avoidance chamber during testing. Gestational stress reduced time spent interacting with a conspecific. These data suggest that gestational and acute restraint stress can have actions to produce behavioral inhibition coincident with increased corticosterone and decreased 5?-reduced androgens of adult male rats. Thus, gestational stress altered neural circuits involved in the neuroendocrine response to acute stress in early adulthood. PMID:23264760

Walf, Alicia A; Frye, Cheryl A

2012-12-18

183

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

PubMed Central

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

Walf, Alicia A.; Frye, Cheryl A.

2012-01-01

184

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

PubMed Central

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

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

2009-01-01

185

Postconditioning by mild hypoxic exposures reduces rat brain injury caused by severe hypoxia.  

PubMed

A potent neuroprotective effect of ischemic postconditioning has previously been described using cerebral artery occlusion but this is not a practical therapeutic option. The present study has been performed to determine whether postconditioning by mild episodes of hypobaric hypoxia (hypoxic postconditioning, HP) can reduce post-hypoxic brain injury in rats. Male Wistar rats were submitted to severe hypobaric hypoxia (180 Torr, 3 h) followed by HP (360 Torr, 2 h, 3 trials spaced at 24 h) starting either 3h (early HP) or 24 h (delayed HP) after severe hypoxia. The structural and functional brain injury was assessed by a complex of histological techniques, behavioral methods, and by testing the functions of the hypothalamic-pituitary-adrenal axis (HPA). It was found that early and delayed HP considerably attenuated post-hypoxic injury, reducing pyknosis, hyperchromatosis, and interstitial brain edema, as well as the rates of neuronal loss in hippocampus and neocortex. Delayed HP produced prominent anxiolytic effect on rat behavior, preventing development of post-hypoxic anxiety. Both modes of HP had beneficial effect on the functioning of HPA, but only delayed HP normalized completely the baseline HPA activity and its reactivity to stress. The results obtained demonstrate that postconditioning by using repetitive episodes of mild hypobaric hypoxia may provide a powerful neuroprotective procedure that can be easily adopted for clinical practice and recommended as a research tool for identification of endogenous mechanisms involved in post-ischemic neuroprotection. PMID:22366259

Rybnikova, Elena; Vorobyev, Maksim; Pivina, Svetlana; Samoilov, Mikhail

2012-02-15

186

Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats  

PubMed Central

Background Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. Methods Sixty-four rats were randomized in two groups and laparotomized. One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline. Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured. Body weight, food and water intake were also recorded daily. Results HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 ± 90.25 micromol HCl vs. 1247 ± 152. P = 0.0017). Botulinum toxin-treated rats also showed significantly lower food intake and weight gain. Conclusions Botulinum toxin type A reduces stimulated gastric acidity. This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses. Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility.

Runfola, Matteo; Rossi, Simone; Panunzi, Simona; Spada, Pier Luigi; Gui, Daniele

2003-01-01

187

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

PubMed Central

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

Lujan, Heidi L.; Krishnan, Sandhya

2011-01-01

188

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

189

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

Microsoft Academic Search

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

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

2004-01-01

190

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

PubMed

The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.5% prilocaine), alcaine (.5% proparacaine), triocaine (20% benzocaine, 6% lidocaine, and 4% tetracaine), or petroleum jelly (treatment control). Touch thresholds significantly increased after treatment with EMLA 18% of the time, and there was no evidence of a systemic effect. Touch thresholds were not significantly altered after treatment with alcaine, triocaine, or petroleum jelly. Therefore, EMLA appears to be a slightly effective topical anesthetic for reducing tactile sensitivity in newborn rats. © 2012 Wiley Periodicals, Inc. Dev Psychobiol. PMID:23254968

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

2012-12-19

191

Prolonged local neurotrophin-3 infusion reduces ipsilateral collateral sprouting of spared corticospinal axons in adult rats.  

PubMed

The corticospinal tract is widely used to study regeneration and is essential for voluntary movements in humans. In young rats, corticospinal axons on the uninjured side sprout and grow into the denervated side. Neurotrophin-3 (NT-3) induces such crossed collateral sprouting in adults. We investigated whether local intraspinal NT-3 infusions would promote collateral sprouting of spared corticospinal terminals from within a partially denervated side, as this would be more appropriate for enhancing function of unilateral and specific movements. Adult rats received a partial bilateral transection of the pyramids, leaving approximately 40% of each tract intact. Vehicle or vehicle plus NT-3 (3 or 10 microg/day) was infused for 14 days into the left side of the cervical (C5/6) or lumbar (L2) cord. The corticospinal processes on the left side were anterogradely traced with cholera toxin B (CTB; which labeled gray matter processes more robustly than biotinylated dextran amine) injected into the front or hind limb area of the right sensorimotor cortex, respectively, 3 days before analysis. Unexpectedly, approximately 40% fewer CTB-labeled corticospinal processes were detectable in the cervical or lumbar gray matter of NT-3-treated rats than in vehicle-infused ones. Vehicle-infused injured rats had more corticospinal processes in the center of the cord than normal rats, evidence for lesion-induced collateral sprouting. NT-3 caused sprouting of local calcitonin gene-related peptide-positive fibers. These results suggest that NT-3 reduces collateral sprouting of spared corticospinal axons from within the denervated regions, possibly because of the injury environment or by increasing sprouting of local afferents. They identify an unexpected context-dependent outgrowth inhibitory effect of NT-3. PMID:15652986

Hagg, T; Baker, K A; Emsley, J G; Tetzlaff, W

2005-01-01

192

THE ?1-ADRENERGIC RECEPTOR ANTAGONIST, PRAZOSIN, REDUCES ALCOHOL DRINKING IN ALCOHOL-PREFERRING (P) RATS  

PubMed Central

BACKGROUND Preliminary evidence suggest that noradrenergic signaling may play a role in mediating alcohol drinking behavior in both humans and rats. Accordingly, we tested the hypothesis that blockade of ?1-adrenergic receptors will suppress alcohol drinking in rats selectively bred for alcohol preference (P line). METHODS Adult male P rats were given 24-hour access to food and water and scheduled access to a 15% (v/v) alcohol solution for two hours daily. Rats were injected IP with the ?1-adrenergic receptor antagonist, prazosin (0, 0.5, 1.0, 1.5 or 2.0 mg/kg BW), once a day at 15 min prior to onset of the daily two hour two-bottle choice, alcohol versus water, access period for two consecutive days and then three weeks later for five consecutive days. RESULTS Prazosin significantly reduced (p<0.01) alcohol intake during the initial two daily administrations, and this reduction of alcohol intake was maintained for five consecutive days by daily prazosin treatment in the subsequent more prolonged trial (p<0.05). The prazosin-induced reduction of alcohol intake was not dependent upon drug-induced motor impairment since increases in water drinking (p<0.05) were exhibited during the two hour access periods during both two day and five day prazosin treatment. CONCLUSIONS The results indicate that the noradrenergic system plays a role in mediating alcohol drinking in rats of the P line, and suggest that prazosin - a safe, well-characterized and well-tolerated drug - may be an effective pharmacotherapeutic agent for the treatment of alcohol use disorders.

Rasmussen, Dennis D.; Alexander, Laura L.; Raskind, Murray A.; Froehlich, Janice C.

2009-01-01

193

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

PubMed

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

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

2011-06-15

194

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

PubMed

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 the 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 grey 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 grey 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 grey 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

2012-12-20

195

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

PubMed Central

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

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

2013-01-01

196

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

PubMed Central

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

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

2003-01-01

197

Careful climbing in the Miocene: the forelimbs of Ardipithecus ramidus and humans are primitive.  

PubMed

The Ardipithecus ramidus hand and wrist exhibit none of the derived mechanisms that restrict motion in extant great apes and are reminiscent of those of Miocene apes, such as Proconsul. The capitate head is more palmar than in all other known hominoids, permitting extreme midcarpal dorsiflexion. Ar. ramidus and all later hominids lack the carpometacarpal articular and ligamentous specializations of extant apes. Manual proportions are unlike those of any extant ape. Metacarpals 2 through 5 are relatively short, lacking any morphological traits associable with knuckle-walking. Humeral and ulnar characters are primitive and like those of later hominids. The Ar. ramidus forelimb complex implies palmigrady during bridging and careful climbing and exhibits none of the adaptations to vertical climbing, forelimb suspension, and knuckle-walking that are seen in extant African apes. PMID:19810196

Lovejoy, C Owen; Simpson, Scott W; White, Tim D; Asfaw, Berhane; Suwa, Gen

2009-10-01

198

Comparative study of the tissue distribution of NADH and NADPH-dependent chloral hydrate reducing enzymes in the rat  

SciTech Connect

Chloral hydrate (CH), an intermediate metabolite of trichloroethylene, is reduced to trichloroethanol (TCE) by alcohol dehydrogenase and aldehyde reductase. Alcohol dehydrogenase requires reduced nicotinamide adenine dinucleotide (NADH), and aldehyde reductase requires reduced nicotinamide adenine dinucleotide phosphate (NADPH). No reports have appeared concerning comparative studies of the tissue distribution of CH-reducing enzymes. In this report, NADH and NADPH-dependent CH-reducing activities were investigated in various organs of the rat.

Ogino, Keiki; Hobara, Tatsuya; Kobayashi, Haruo; Iwamoto, Susumu (Yamaguchi Univ. School of Medicine, Kogushi Ube (Japan))

1990-03-01

199

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

PubMed

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

Lewin, G A; Smith, J H

2010-01-11

200

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

201

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

PubMed

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

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

2009-12-01

202

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.

Fujiwara, Shin-ichi; Hutchinson, John R.

2012-01-01

203

Agmatine Reduces Ultrasonic Vocalization Deficits in Female Rat Pups Exposed Neonatally to Ethanol  

PubMed Central

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 20 mg/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.

Wellmann, Kristen; Lewis, Ben; Barron, Susan

2010-01-01

204

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

PubMed

The aim of this study was to determine and compare the effects of both magnesium citrate and phytin on reducing urinary calcium excretion under high-calcium-diet conditions during single and combined treatments. An animal experiment was carried out over a period of 4 weeks in 35 male rats. Urinary calcium excretion was reduced significantly by magnesium citrate and/or phytin in rats fed on high-calcium diets. The hypocalciuric effect of magnesium citrate was more evident than that of phytin. Urinary magnesium excretion was high in all experimental groups. However, the urinary magnesium/calcium ratios showed a consistent increase only in the groups treated with magnesium citrate. Urinary citrate excretion showed a relative increase with the introduction of magnesium citrate plus phytin; however, in both the high-calcium-diet group and the magnesium-citrate group this was found to be reduced. Urinary phosphate excretion was slightly higher in the groups treated with phytin. There was no definite difference in urinary oxalate concentration between the groups. No significant change was noted in the serum concentration of calcium, magnesium, or phosphate. PMID:7881470

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

1994-01-01

205

Nitecapone reduces development and symptoms of neuropathic pain after spinal nerve ligation in rats.  

PubMed

Neuropathic pain is caused by damage or malfunctioning of the nervous system. It is fairly common and more resistant to treatment than other types of pain. Since nitecapone, an inhibitor of catechol-O-methyl-transferase (COMT), has decreased neuropathic symptoms in diabetic rats, we studied its effects in another model of neuropathic pain, the spinal nerve ligation (SNL) model. Spinal nerves L5-6 were ligated in male Wistar rats under anaesthesia to produce the SNL model of neuropathic pain. Nitecapone (30 mg/kg, i.p.) or vehicle was administered once daily starting either 1h before or 2 days after surgery and continued for 14-19 days. Threshold for mechanical allodynia was measured with the digital von Frey test and responses to cold stimuli with the acetone test, before surgery and every other day after it 1h before drug administration. Mechanical and cold allodynia developed in all study groups. Both nitecapone treatments significantly reduced mechanical allodynia and withdrawal thresholds were 80-95% higher compared with the control group. In the acetone test, both nitecapone groups also showed less signs of cold allodynia than the control groups. In nitecapone-naïve animals a single dose of nitecapone also reduced mechanical allodynia on the 14th day after the surgery. Nitecapone reduced the symptoms of neuropathic pain after the SNL, which is in line with the earlier study. Our results suggest that nitecapone and other COMT inhibitors should be studied further in the treatment of neuropathic pain. PMID:21216640

Kambur, Oleg; Männistö, Pekka T; Pusa, Anne M; Käenmäki, Mikko; Kalso, Eija A; Kontinen, Vesa K

2011-01-08

206

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.

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

207

FK 506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat.  

PubMed

We examined the efficacy of FK 506 in reducing tissue damage after spinal cord injury in comparison to methylprednisolone (MP) treatment. Rats were subjected to a photochemical injury (T8) and were given a bolus of MP (30 mg/kg), FK 506 (2 mg/kg), or saline. An additional group received an initial bolus of FK 506 (2 mg/kg) followed by daily injections (0.2 mg/kg intraperitoneally). Functional recovery was evaluated using open-field walking, inclined plane tests, motor evoked potentials (MEPs), and the H-reflex response during 14 days postoperation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEC, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1 beta) immunoreactivity were quantified in the injured spinal cord. FK 506-treated animals demonstrated significantly better neurologic outcome, higher MEP amplitudes, and lower H-wave amplitude compared to that of saline-treated rats. In contrast, administration of MP did not result in significant differences with respect to the saline-treated group. Histologic examination revealed that tissue sparing was largest in FK 506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK 506 compared to that in animals given MP or saline, whereas IL-1 beta expression was similarly reduced in both FK 506- and MP-treated groups. Microglia/macrophage response was reduced in FK 506 and MP-injected animals at 3 dpo, but only in MP-treated animals at 7 dpo with respect to saline-injected rats. Repeated administrations of FK 506 improved functional and histologic results to a greater degree than did a single bolus of FK 506. The results indicate that FK 506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries. PMID:16041804

López-Vales, Rubèn; García-Alías, Guillermo; Forés, Joaquim; Udina, Esther; Gold, Bruce G; Navarro, Xavier; Verdú, Enrique

2005-09-15

208

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

PubMed Central

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

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

2012-01-01

209

6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant  

PubMed Central

Background 6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200–250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). Results Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 ± 0.2 mm to 1.0 ± 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 ± 0.6 mm to 0.8 ± 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 ± 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. Conclusion From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.

Levy, Arkene SA; Simon, Oswald; Shelly, Janet; Gardener, Michael

2006-01-01

210

Low Frequency Stimulation of Hippocampal Commissures Reduces Seizures in Chronic Rat Model of Temporal Lobe Epilepsy  

PubMed Central

SUMMARY Purpose To investigate the effects of low frequency stimulation (LFS) of a fiber track for the suppression of spontaneous seizures described by Nissinen in a rat model of human temporal lobe epilepsy. Methods Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recordings electrodes were placed in the CA3 regions bilaterally and neural data was recorded for a minimum of six weeks. LFS (60 minute train of 1Hz biphasic square wave pulses, each 0.1ms in duration and 200?A in amplitude, followed by 15 minutes of rest) was applied to the VHC for, two weeks, 24 hours a day. Key Findings The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n=7). By the end of the two-week period of stimulation, there was a significant 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during two weeks LFS session. The hippocampal histological analysis showed no significant difference between rats that received LFS and SE-induction and those that had only received SE-induction. None of the animals showed any symptomatic hemorrhage, infection or complication. Significance LFS applied at a frequency of 1Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could be lead to the development of the new therapeutic modality for human patients with temporal lobe epilepsy.

Rashid, Saifur; Pho, Gerald; Czigler, Michael; Werz, Mary Ann; Durand, Dominique M.

2013-01-01

211

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

PubMed

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

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

2011-11-29

212

Reduced activity of muscle Na(+)-K(+)-ATPase after prolonged running in rats.  

PubMed

The purpose of this study was to investigate the hypothesis that Na(+)-K(+)-ATPase activity is reduced in muscle of different fiber composition after a single session of aerobic exercise in rats. In one experiment, untrained female Sprague-Dawley rats (weight 275 +/- 21 g; means +/- SE; n = 30) were run (Run) on a treadmill at 21 m/min and 8% grade until fatigue, or to a maximum of 2 h, which served as control (Con), or performed an additional 45 min of low-intensity exercise at 10 m/min (Run+). In a second experiment, utilizing rats of similar characteristics (weight 258 +/- 18 g; n = 32), Run was followed by passive recovery (Rec). Directly after exercise, rats were anesthetized, and tissue was extracted from Soleus (Sol), red vastus lateralis (RV), white vastus lateralis (WV), and extensor digitorum longus (EDL) and frozen for later analysis. 3-O-methylfluorescein phosphatase activity (3-O-MFPase) was determined as an indicator of Na(+)-K(+)-ATPase activity, and glycogen depletion identified recruitment of each muscle during exercise. 3-O-MFPase was decreased (P < 0.05) at Run+ by an average of 12% from Con in all muscles (P < 0.05). No difference was found between Con and Run. Glycogen was lower (P < 0.05) by 65, 57, 44, and 33% (Sol, EDL, RV, and WV, respectively) at Run, and there was no further depletion during the continued low-intensity exercise period. No differences in Na(+)-K(+)-ATPase activity was observed between Con and Rec. The results of this study indicate that inactivation of Na(+)-K(+)-ATPase can be induced by aerobic exercise in a volume-dependent manner and that the inactivation that occurs is not specific to muscles of different fiber-type composition. Inactivation of Na(+)-K(+)-ATPase suggests intrinsic structural modifications by mechanisms that are unclear. PMID:12381757

Fowles, J R; Green, H J; Schertzer, J D; Tupling, A R

2002-11-01

213

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.

Anker, Justin J.; Carroll, Marilyn E.

2013-01-01

214

Reduced vascular responsiveness to adiponectin in hyperlipidemic rats--mechanisms and significance.  

PubMed

Deficiency of adiponectin (APN), an adipocyte-derived vascular protective molecule, contributes to diabetic vascular injury. The current study determined whether obesity/hyperlipidemia may alter the vascular response to APN, and investigated the involved mechanisms and pathologic significance. Adult male Sprague-Dawley rats were fed a regular or high-fat diet (HF) for 4-16 weeks. Circulating APN levels, aortic pAMPK/AMPK, peNOS/eNOS, and APN receptor expression levels were determined. Compared to time-matched animals fed control diet, plasma APN levels in HF-diet animals were significantly increased at 8 weeks, and rapidly declined thereafter. Despite unchanged or elevated circulating APN levels, phosphorylated AMPK and eNOS in vascular tissue were significantly reduced at all observed time points. Recombinant full-length APN (rAPN)-induced AMPK/eNOS phosphorylation and vasodilatation were significantly reduced in 16-week obese/hyperlipidemic aortic segments. Vascular APN receptor 1 (AdipoR1) and receptor 2 (AdipoR2) expression were significantly reduced 16 weeks after HF-diet. Pre-incubation of rAPN with obese/hyperlipidemic plasma, but not with normal plasma, significantly reduced its AMPK and eNOS activation effect, and blunted its protective effect against TNFalpha-induced HUVEC apoptosis. This study demonstrated for the first time that obesity/hyperlipidemia reduces vascular responsiveness to APN. Modification/inactivation of APN by unidentified factors present in obese/hyperlipidemic plasma, decreased vascular AdipoR1/R2 expression, and reduced circulating APN levels contribute to reduced vascular responsiveness to APN at different stages of the obese condition. Reduced APN bioactivity allows unmitigated TNFalpha pro-apoptotic and pro-inflammatory actions, contributing to vascular injury in obesity/hyperlipidemia. PMID:20303976

Li, Rong; Xu, Ming; Wang, Xiaoliang; Wang, Yajing; Lau, Wayne Bond; Yuan, Yuexing; Yi, Wei; Wei, Xuefeng; Lopez, Bernard L; Christopher, Theodore A; Wang, Xiao-Ming; Ma, Xin-Liang

2010-03-18

215

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

PubMed Central

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

Li, Jing; LaMarca, Babbette

2012-01-01

216

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

217

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

PubMed Central

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

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

2011-01-01

218

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

PubMed

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

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

2013-07-17

219

Heliox and oxygen reduce infarct volume in a rat model of focal ischemia.  

PubMed

Normobaric hyperoxia treatment has recently been demonstrated to be remarkably beneficial in acute focal ischemia. The present study compared hyperoxia treatment with a novel heliox treatment. Adult male rats breathed 30% oxygen and 70% nitrogen (control group), 100% oxygen (hyperoxia group), or 30% oxygen and 70% helium (heliox group) during a middle cerebral artery occlusion for 2 h and a 1-hour reperfusion (n=6 in each group). Neurological deficits were scored at 3 and 24 h post focal ischemia. Neither the physiological parameters (body temperature, blood pressure, heart rate, O(2) saturation, and laser Doppler cerebral blood) nor the 3-hour post ischemia neurological scores differed between groups. However, the neurological scores showed a statistically significant improvement at 24 h post ischemia in the heliox group (p<0.05). The infarct volume (mean+SD) as measured by 2,3,5-triphenyltetrazolium staining included 36+/-17% of the involved hemisphere in the control group, 16+/-14% in the hyperoxia group, and 4+/-2% in the heliox group (p<0.01). In conclusion, whereas hyperoxia reduced the infarct volume, heliox further reduced the infarct volume and improved 24-hour neurological deficits in a rat model of focal ischemia. This suggests that a greater benefit may accrue from heliox therapy. PMID:17467695

Pan, Yi; Zhang, Haibo; VanDeripe, Donald R; Cruz-Flores, Salvador; Panneton, W Michael

2007-03-30

220

Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats.  

PubMed

Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors. Male, aged, lean, and corpulent rats exposed to transient (90 minutes) occlusion of the middle cerebral artery (tMCAO) were administered two doses of IL-1Ra (25 mg/kg, subcutaneously) during reperfusion. Brain injury and neuroinflammatory changes were assessed 24 hours after tMCAO. Our results show that IL-1Ra administered at reperfusion significantly reduced infarct volume measured by magnetic resonance imaging (50%, primary outcome) and blood-brain barrier disruption in these comorbid animals. Interleukin-1Ra also reduced microglial activation, neutrophil infiltration, and cytokines levels in the brain. These data are the first to indicate that IL-1Ra protects against ischemic brain injury when administered via a clinically relevant route and time window in animals with multiple risk factors for stroke. PMID:22781338

Pradillo, Jesus M; Denes, Adam; Greenhalgh, Andrew D; Boutin, Herve; Drake, Caroline; McColl, Barry W; Barton, Eleanor; Proctor, Spencer D; Russell, James C; Rothwell, Nancy J; Allan, Stuart M

2012-07-11

221

Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats  

PubMed Central

Many neuroprotective agents have been effective in experimental stroke, yet few have translated into clinical application. One reason for this may be failure to consider clinical comorbidities/risk factors in experimental models. We have shown that a naturally occurring interleukin-1 receptor antagonist (IL-1Ra) is protective against ischemic brain damage in healthy animals. However, protective effects of IL-1Ra have not been determined in comorbid animals. Thus, we tested whether IL-1Ra protects against brain injury induced by experimental ischemia in aged JCR-LA (corpulent) rats, which have clinically relevant risk factors. Male, aged, lean, and corpulent rats exposed to transient (90?minutes) occlusion of the middle cerebral artery (tMCAO) were administered two doses of IL-1Ra (25?mg/kg, subcutaneously) during reperfusion. Brain injury and neuroinflammatory changes were assessed 24?hours after tMCAO. Our results show that IL-1Ra administered at reperfusion significantly reduced infarct volume measured by magnetic resonance imaging (50%, primary outcome) and blood–brain barrier disruption in these comorbid animals. Interleukin-1Ra also reduced microglial activation, neutrophil infiltration, and cytokines levels in the brain. These data are the first to indicate that IL-1Ra protects against ischemic brain injury when administered via a clinically relevant route and time window in animals with multiple risk factors for stroke.

Pradillo, Jesus M; Denes, Adam; Greenhalgh, Andrew D; Boutin, Herve; Drake, Caroline; McColl, Barry W; Barton, Eleanor; Proctor, Spencer D; Russell, James C; Rothwell, Nancy J; Allan, Stuart M

2012-01-01

222

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

PubMed

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

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

2013-06-06

223

Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats.  

PubMed

The CB1 receptor antagonist, rimonabant, affects the endocannabinoid system and causes a sustained reduction in body weight (BW) despite the transient nature of the reduction in food intake. Therefore, in a multiple-dose study, female candy-fed Wistar rats were treated with rimonabant (10 mg/kg) and matched with pair-fed rats to distinguish between hypophagic action and hypothesized effects on energy expenditure. Within the first week of treatment, rimonabant reduced BW nearly to levels of standard rat chow-fed rats. Evaluation of energy balance (energy expenditure measured by indirect calorimetry in relation to metabolizable energy intake calculated by bomb calorimetry) revealed that increased energy expenditure based on increased fat oxidation contributed more to sustained BW reduction than reduced food intake. A mere food reduction through pair feeding did not result in comparable effects because animals reduced their energy expenditure to save energy stores. Because fat oxidation measured by indirect calorimetry increased immediately after dosing in the postprandial state, the acute effect of rimonabant on lipolysis was investigated in postprandial male rats. Rimonabant elevated free fatty acids postprandially, demonstrating an inherent pharmacological activity of rimonabant to induce lipolysis and not secondarily postabsorptively due to reduced food intake. We conclude that the weight-reducing effect of rimonabant was due to continuously elevated energy expenditure based on increased fat oxidation driven by lipolysis from fat tissue as long as fat stores were elevated. When the amount of endogenous fat stores declined, rimonabant-induced increased energy expenditure was maintained by a re-increase in food intake. PMID:18276749

Herling, Andreas W; Kilp, Susanne; Elvert, Ralf; Haschke, Guido; Kramer, Werner

2008-02-14

224

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

PubMed Central

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

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

2013-01-01

225

Eribis peptide 94 reduces infarct size in rat hearts via activation of centrally located ? opioid receptors.  

PubMed

Eribis peptide 94 (EP 94) is a novel enkephalin derivative that binds with high potency to ? and ? opioid receptors with less affinity for the ? opioid receptor. This compound has recently been shown to produce an acute reduction in myocardial infarct size in the anesthetized pig and rat partially via an endothelial nitric oxide synthase and KATP channel-dependent mechanism. EP 94 also was found to produce a chronic reduction in infarct size 24 hours postdrug administration via the upregulation of inducible nitric oxide synthase in rats. Despite these findings, no data have emerged in which the opioid receptor subtype responsible for cardioprotection has been identified and the site of action, heart, other peripheral organs, or the central nervous system, has not been addressed. In the current study, EP 94, was administered in 2 divided doses (0.5 ?g/kg, intravenously) at 5 and 10 minutes into the ischemic period, and the opioid antagonists were administered 10 minutes before the onset of the 30-minute ischemic period. The selective antagonists used were the ? receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2), the ? receptor antagonists naltrindole and BNTX (7-benzylidenenaltrexone), and the ? receptor antagonist nor-BNI (norbinaltorphimine). Surprisingly, only CTOP completely blocked the cardioprotective effect of EP 94, whereas naltrindole, BNTX, and nor-BNI had modest but nonsignificant effects. Because there is controversial evidence suggesting that ? receptors may be absent in the adult rat myocardium, it was hypothesized that the protective effect of EP 94 may be mediated by an action outside the heart, perhaps in the central nervous system. To test this hypothesis, rats were pretreated with the nonselective opioid antagonist, naloxone hydrochloride, which penetrates the blood-brain barrier or naloxone methiodide, the quaternary salt of naloxone hydrochloride, which does not penetrate the blood-brain barrier before EP 94 administration. In support of a central nervous system site of action for EP 94, naloxone hydrochloride completely blocked its cardioprotective effect, whereas naloxone methiodide had no effect. These results suggest that EP 94 reduces infarct size (expressed as a percent of the area at risk) in the rat primarily via activation of central ? opioid receptors. PMID:22130105

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

2012-02-01

226

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

PubMed Central

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

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

2011-01-01

227

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

PubMed

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

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

2007-05-29

228

Prostaglandin E2 reduces amyloid beta-induced phagocytosis in cultured rat microglia.  

PubMed

Treatment with amyloid beta(1-42) (Abeta(1-42)) at 1microM for 60min increased phagocytosis of latex beads by cultured rat microglia. This increase was reduced dose-dependently by prostaglandin E(2) (PGE(2)), but PGD(2), PGF(2alpha), iloprost, or U-46619 had no effects. PGE(2) also reduced the phagocytosis of fluorescent-labeled Abeta(1-42). Abeta(1-42)-induced phagocytosis was reduced by butaprost but not by 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol. The reduction effect of PGE(2) on phagocytosis was reversed by AH6809, an E-prostanoid receptor 2 (EP2) antagonist, which inhibited cyclic adenosine monophosphate (AMP) accumulation induced by PGE(2). Butaprost, but not 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol increased intracellular cyclic AMP accumulation. In western blotting analysis, EP2-like immunoreactivity was detected in the crude membrane fraction of microglia. On the other hand, Abeta(1-42)-induced phagocytosis was not affected by SC-560, a cyclooxygenase-1 (COX-1) inhibitor, NS-398, a COX-2 inhibitor, or ibuprofen, a non-specific COX inhibitor. Abeta(1-42) or PGE(2) had little effect on the expression levels of COX-1 or COX-2. These results indicate that Abeta(1-42)-induced microglial phagocytosis is reduced by PGE(2) through EP2. PMID:20144888

Nagano, Takayuki; Kimura, Shinya H; Takemura, Motohiko

2010-02-06

229

Prostaglandin E2 reduces extracellular ATP-induced migration in cultured rat microglia.  

PubMed

Treatment with 100 microM adenosine triphosphate (ATP) for 120 min augmented migration of cultured rat microglia by about 4-fold. This augmentation was effectively reduced by 0.1-10 microM prostaglandin E(2) (PGE(2)). PGE(2)-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 microM. The EP2 agonist butaprost also reduced ATP-induced migration at 10 microM, whereas the EP1 agonist 17-phenyl trinor PGE(2), the EP3 agonist sulprostone, and the EP4 agonist PGE(1) alcohol all had no effect at 10 microM. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 microM, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE(2) on ATP-induced migration at 100 microM. Over the same experimental duration, PGE(2), butaprost, and forskolin had little effect on cell viability. These findings indicate that ATP-induced microglial migration is reduced by PGE(2) through EP2 and adenylate cyclase. PMID:18565497

Nagano, Takayuki; Kimura, Shinya H; Takemura, Motohiko

2008-05-18

230

Treatment with ginseng total saponins reduces the secondary brain injury in rat after cortical impact.  

PubMed

The present study was designed to investigate the neuroprotective effect of ginseng total saponins (GTSs) and its underlying mechanisms in a rat model of traumatic brain injury (TBI). Rats were injected with GTSs (20 mg/kg, i.p.) or vehicle for 14 days after TBI. Neurological functions were determined using beam balance and prehensile traction tests at 1-14 days after trauma. Brain samples were extracted at 1 day after trauma for determination of water content, Nissl staining, enzyme-linked immunosorbent assay, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling, and measurement of oxidative stress variables and inflammatory cytokines. Moreover, the dose response of the neuroprotective effect and time window of the efficacy of GTSs were also determined. We found that treatment of GTSs 1) improved the neurological function with an effective dosage of 5-80 mg/kg and an efficacy time window of 3-6 hr after TBI; 2) reduced brain water content and neuronal loss in the hippocampal CA3 area; 3) increased the activity of superoxide dismutase and decreased the activity of nitric oxide synthase and the amount of malondialdehyde and nitric oxide; 4) down-regulated interleukin-1?, interleukin-6, and tumor necrosis factor-? and upregulated interleukin-10 in the cortical area surrounding the injured core; and 5) inhibited the apoptotic cell death and expression of caspase-3 and bax and raised the expression of bcl-2. These findings suggest that administration of GTSs after TBI could reduce the secondary injury through inhibiting oxidative and nitrative stress, attenuating inflammatory response, and reducing apoptotic cell death. PMID:22434648

Xia, Lei; Jiang, Zheng-Lin; Wang, Guo-Hua; Hu, Bao-Yin; Ke, Kai-Fu

2012-03-21

231

Losartan reduces oxidative stress within the rostral ventrolateral medulla of rats with renovascular hypertension.  

PubMed

BACKGROUND : Previous studies showed that the microinjection of antioxidants or the overexpression of superoxide dismutase within the rostral ventrolateral medulla (RVLM) reduces hypertension and sympathoexcitation in the 2-kidney, 1-clip (2K-1C) model. In this study, we hypothesized that angiotensin II (ANG II) type 1 receptor (AT1R) is involved in the oxidative stress within the RVLM and contributes to cardiovascular dysfunction in renovascular hypertension. METHODS : Losartan (30mg/kg/day, oral gavage) was administered for 7 consecutive days by week 5 after implantation of the clip (gap width = 0.2mm). Mean arterial pressure, baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated. Superoxide production was evaluated by dihydroethidium (DHE) staining within the RVLM and within a control area. Systemic oxidative stress was characterized by measurement of thiobarbituric acid reactive substances (TBARS) and total glutathione (tGSH) in the blood. RESULTS : AT1R blockade significantly (P < 0.05) reduced hypertension by approximately 20% (n = 11) and sympathoexcitation to the kidneys by approximately 41% (n = 6) in the 2K-1C rats. Losartan treatment increased the baroreflex sensitivity of rSNA to pressor (67%) and depressor (140%) stimuli in the 2K-1C rats. AT1R blockade caused a significant (66%) reduction in DHE staining within the RVLM but not within the control area, reduced plasma TBARS (from 1.6±0.1 to 1.0±0.1 nmol/ml), and increased tGSH (from 3.4±0.4 to 5.2±0.3 ?mol/g Hb) in the 2K-1C group only. CONCLUSIONS : Our findings suggest that the beneficial effects of ANG II blockade in renovascular hypertension are partly due to preferential reduction of oxidative stress in the RVLM. PMID:23485486

Nishi, Erika E; Bergamaschi, Cássia T; Oliveira-Sales, Elizabeth B; Simon, Karin A; Campos, Ruy R

2013-03-13

232

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

2013-08-19

233

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.

Kristensen, Mette; Bach Knudsen, Knud Erik; J?rgensen, Henry; Oomah, David; Bugel, Susanne; Toubro, S?ren; Tetens, Inge; Astrup, Arne

2013-01-01

234

Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice.  

PubMed

The zinc-finger transcriptional repressor Blimp1 (Prdm1) controls gene expression patterns during differentiation of B lymphocytes and regulates epigenetic changes required for specification of primordial germ cells. Blimp1 is dynamically expressed at diverse tissue sites in the developing mouse embryo, but its functional role remains unknown because Blimp1 mutant embryos arrest at E10.5 due to placental insufficiency. To explore Blimp1 activities at later stages in the embryo proper, here we used a conditional inactivation strategy. A Blimp1-Cre transgenic strain was also exploited to generate a fate map of Blimp1-expressing cells. Blimp1 plays essential roles in multipotent progenitor cell populations in the posterior forelimb, caudal pharyngeal arches, secondary heart field and sensory vibrissae and maintains key signalling centres at these diverse tissues sites. Interestingly, embryos carrying a hypomorphic Blimp1gfp reporter allele survive to late gestation and exhibit similar, but less severe developmental abnormalities, whereas transheterozygous Blimp1(gfp/-) embryos with further reduced expression levels, display exacerbated defects. Collectively, the present experiments demonstrate that Blimp1 requirements in diverse cell types are exquisitely dose dependent. PMID:18039967

Robertson, Elizabeth J; Charatsi, Iphigenie; Joyner, Clive J; Koonce, Chad H; Morgan, Marc; Islam, Ayesha; Paterson, Carol; Lejsek, Emily; Arnold, Sebastian J; Kallies, Axel; Nutt, Stephen L; Bikoff, Elizabeth K

2007-12-01

235

Ultrasonically-assisted intracortical microstimulation of the rat  

Microsoft Academic Search

High frequency tone bursts of ultrasound are capable of increasing the sensitivity of rat motor cortex to electrical stimulation. In this study, 11.75 MHz ultrasound pre-stimuli were delivered to the forelimb motor region of the rat cortex followed by an electrical pulse train to assess changes in cortical activation. The temporal peak intensity of the ultrasound delivered to the brain

William B. Phillips; Patrick J. Larson; Bruce C. Towe

2004-01-01

236

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

PubMed Central

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

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

2013-01-01

237

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

PubMed Central

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

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

2011-01-01

238

Ceftriaxone, a Beta-Lactam Antibiotic, Reduces Ethanol Consumption in Alcohol-Preferring Rats  

PubMed Central

Aims: Changes in glutamatergic transmission affect many aspects of neuroplasticity associated with ethanol and drug addiction. For instance, ethanol- and drug-seeking behavior is promoted by increased glutamate transmission in key regions of the motive circuit. We hypothesized that because glutamate transporter 1 (GLT1) is responsible for the removal of most extracellular glutamate, up-regulation or activation of GLT1 would attenuate ethanol consumption. Methods: Alcohol-preferring (P) rats were given 24 h/day concurrent access to 15 and 30% ethanol, water and food for 7 weeks. During Week 6, P rats received either 25, 50, 100 or 200 mg/kg ceftriaxone (CEF, i.p.), a ?-lactam antibiotic known to elevate GLT1 expression, or a saline vehicle for five consecutive days. Water intake, ethanol consumption and body weight were measured daily for 15 days starting on Day 1 of injections. We also tested the effects of CEF (100 and 200 mg/kg, i.p.) on daily sucrose (10%) consumption as a control for motivated behavioral drinking. Results: Statistical analyses revealed a significant reduction in daily ethanol, but not sucrose, consumption following CEF treatment. During the post treatment period, there was a recovery of ethanol intake across days. Dose-dependent increases in water intake were manifest concurrent with the CEF-induced decreases in ethanol intake. Nevertheless, CEF did not affect body weight. An examination of a subset of the CEF-treated ethanol-drinking rats, on the third day post CEF treatment, revealed increases in GTL1 expression levels within the prefrontal cortex and nucleus accumbens. Conclusions: These results indicate that CEF effectively reduces ethanol intake, possibly through activation of GLT1, and may be a potential therapeutic drug for alcohol addiction treatment.

Sari, Youssef; Sakai, Makiko; Weedman, Jason M.; Rebec, George V.; Bell, Richard L.

2011-01-01

239

The Reducing Effects of a Calcium-Deficient Diet and High Sucrose Diet on Dentin Apposition of Rat Molars  

Microsoft Academic Search

.   A high sucrose diet reduces dentin apposition of growing rats. The mechanisms of reduction are unclear, but disturbances\\u000a in calcium balance or in mineralization of predentin may explain them. In this experiment, 29 Sprague-Dawley rats, 21 days\\u000a old, were weaned and randomized into calcium-deficient, high-sucrose or standard-diet groups for 3 weeks. They were given\\u000a food and water ad libitum.

E. Pekkala; E.-L. Hietala; M. Puukka; M. Larmas

2000-01-01

240

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

Microsoft Academic Search

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

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

2000-01-01

241

Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.  

PubMed

Aim:To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA).Methods:Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.Results:The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks.Conclusion:The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA. PMID:23334238

Yu, De-gang; Ding, Hui-feng; Mao, Yuan-qing; Liu, Ming; Yu, Bo; Zhao, Xin; Wang, Xiao-qing; Li, Yang; Liu, Guang-wang; Nie, Shao-bo; Liu, Shen; Zhu, Zhen-an

2013-01-21

242

Endothelium-derived nitric oxide reduces baseline venous tone in awake instrumented rats.  

PubMed

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects of intravenous NG-monomethyl-L-arginine (L-NMMA) (3-25 mg/kg), an EDRF inhibitor, on mean circulatory filling pressure (MCFP) were determined in 10 awake instrumented rats. MCFP, the equilibrated systemic pressure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capacitance. L-NMMA caused a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L-NMMA on MCFP were reversed with L-arginine. In an additional four rats, in which hexamethonium was administered to induce ganglionic blockade, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as during the control unblocked state. These findings suggest that nitric oxide, which is likely EDRF, reduces baseline venous tone. PMID:8102035

Glick, M R; Gehman, J D; Gascho, J A

1993-07-01

243

Citrinin reduces testosterone secretion by inducing apoptosis in rat Leydig cells.  

PubMed

A previous study has shown that CTN (Citrinin) inhibits mouse testosterone production. In this study, the mechanism by which testosterone production is inhibited by CTN in rat Leydig cells was investigated, and the morphological evidence of apoptosis, including nuclei fragmentation and phosphatidylserine (PS) exposure on cell surfaces, was clearly observed 36h after CTN exposure. The results showed that citrinin at 50 and 100?M significantly suppressed testosterone secretion by human chorionic gonadotropin (hCG) at 10IU/ml. Western blotting results showed that CTN induced formation of processed p53, caspase-9, and caspase-3 proteins in a dose-dependent manner; CTN also induced a dose-dependent increase in caspase-3 catalytic activity. Western blot assays also showed that CTN decreased expression of three key enzymes (P450scc, 3?-HSD-1, and StAR) of testosterone production. Taken together, these results suggested that CTN reduced testosterone secretion by inducing apoptosis in rat Leydig cells, a mechanism that might account for CTN stimulation of p53 expression followed by activation of multiple caspases. PMID:22564900

Liu, Shuqiang; Wang, Dan; Zhang, Junwen; Zhang, Dongzhi; Gong, Meng; Wang, Chao; Wei, Ning; Liu, Wenhua; Wang, Yongqi; Zhao, Chongxue; Cui, Yaxiong; Hu, Defu

2012-05-04

244

Bifurcations of the respiratory pattern associated with reduced lung volume in the rat.  

PubMed

Rats with intact vagal reflexes exhibit patterns of breathing that contain greater degrees of freedom than those seen after vagotomy. To determine how alterations in end-expiratory volume modify the respiratory pattern, continuous positive (CPAP) and negative (CNAP) airway pressure was applied to tracheal openings of nine urethan-anesthetized vagi-intact rats (+3 to -9 cmH2O). Phase portraits (e.g., volume vs. flow curves), power spectra, correlation integral curves, and inspiratory-to-expiratory duration (TI/TE) ratios are used to interpret the vagal-dependent responses to changes in mean tracheal pressure (Ptr). With CPAP, respiratory oscillation was highly periodic and one dimensional, with TI/TE near 1.0. As Ptr was reduced in a stepwise manner, transient bursts of inspiratory airflow developed local to the expiratory-inspiratory transition, with amplitude increasing proportionally with the level of CNAP. These oscillatory "expiratory interrupts" (doubling TI/TE in five of nine cases) produced highly variable and asymmetric respiratory patterns. Progressive increases in correlation dimension (maximum = 1.8-3.0) and tendencies toward broadband power spectra were seen as Ptr was lowered. The irregular phase-switching dynamics seen with CNAP (which disappeared after vagotomy) are consistent with onset of low-dimensional chaos, probably correlated with activation of feedback mechanisms responsive to lung deflation. PMID:8226495

Sammon, M; Romaniuk, J R; Bruce, E N

1993-08-01

245

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

PubMed Central

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

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

2012-01-01

246

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

PubMed

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

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

2012-02-10

247

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

PubMed Central

Background The forelimb amputee poses many reconstructive challenges in the clinical setting, and there is a paucity of established surgical models for study. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model. Methods Upon approval from the Institutional Animal Care and Use Committee, 5 New Zealand White rabbits underwent left forelimb amputation. During this initial surgery, the median, radial and ulnar nerves were transected 1.6-2.5 (mean 2.0) cm distal to the brachial plexus, transposed onto the anterior chest wall and preserved at length. Six weeks subsequent to the amputation, the distal 5 mm of each neuroma was excised, and the remaining stump underwent histomorphometric analysis. Results The nerve cross sectional areas increased by factors of 1.99, 3.17, and 2.59 in the median (p = 0.077), radial (p < 0.0001) and the ulnar (p = 0.0026) nerves, respectively. At the axonal level, the number and cross-sectional area of myelinated fibers demonstrated an inverse relationship whereby the number of myelinated fibers in the median, radial and ulnar nerves increased by factors of 5.13 (p = 0.0043), 5.25 (p = 0.0056) and 5.59 (p = 0.0027), and the cross-sectional areas of these myelinated fibers decreased by factors of 4.62 (p < 0.001), 3.51 (p < 0.01), and 4.29 (p = 0.0259), respectively. Conclusion Given that the surgical model appears well-tolerated by the rabbits and that patterns of morphologic change are consistent and reproducible, we are encouraged to further investigate the utility of this model in the pathogenesis of neuroma formation.

2010-01-01

248

The selective norepinephrine reuptake inhibitor atomoxetine counteracts behavioral impairments in trimethyltin-intoxicated rats.  

PubMed

This study was carried out to assess the behavioral effects of the non-psychostimulant drug atomoxetine, in rats prenatally-exposed to the organic compound trimethyltin chloride (TMT) and in spontaneously hypertensive rat (SHR), two rodent models of Attention Deficit/Hyperactivity Disorder (ADHD). At birth, neonatal reflexes (righting, cliff aversion, forelimb placing, forelimb grasping, bar holding and startle) had an earlier onset (i.e. percent of appearance) and completion (maximum appearance, i.e. 100% of the brood exhibiting each reflex) in prenatally TMT-exposed and SHR pups as compared to control groups. Two months after birth, TMT-exposed and SHR rats showed impaired cognitive performances in both the step-through passive avoidance test and the shuttle box active avoidance test. Atomoxetine (1, 3 and 6 mg/kg, i.p.), already at the lowest dose tested, improved learning and memory capacity of prenatally TMT-exposed rats and SHR; while methylphenidate (1, 3 and 6 mg/kg, i.p.), used here as positive control, elicited a significant cognitive enhancing effect only at the higher doses. In the open field test, both TMT-exposed rats and SHR displayed enhanced locomotor activity. Methylphenidate further increased locomotor activity in all groups, whereas atomoxetine reduced the enhanced locomotor activity of TMT-exposed rats and SHR down to the level of controls. These results suggest that prenatal TMT-exposure could be considered as a putative experimental model of ADHD and further support the effectiveness of atomoxetine in the ADHD pharmacotherapy. Furthermore, despite the similar effect of the two drugs on cognitive tasks, they exhibit distinct profiles of activity on locomotion, in ADHD models. PMID:22426162

Tamburella, Alessandra; Micale, Vincenzo; Mazzola, Carmen; Salomone, Salvatore; Drago, Filippo

2012-03-08

249

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

PubMed

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

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

2013-02-15

250

Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats.  

PubMed

Carbon tetrachloride-injected rats were given liquid diets with and without betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon tetrachloride (CCl4). Animals were killed and their livers and blood taken for analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate aminotransferase. Liver samples were also processed and stained for histological examination. Supplemental betaine reduced triglyceride in the liver and centrilobular hepatic lipidosis induced by the CCl4 injections. In both the control and experimental groups receiving betaine, liver betaine, BHMT and SAM were significantly higher than in their respective groups not receiving betaine. This study provides evidence that betaine protects the liver against CCl4-induced lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating the harmful effects of CCl4. PMID:9778759

Junnila, M; Barak, A J; Beckenhauer, H C; Rahko, T

1998-10-01

251

Glyburide prevents isoflurane's reducing effects on hydroxyl radical formation in the postischemic reperfused rat heart  

PubMed Central

BACKGROUND: The role of KATP channels in isoflurane’s reducing effects on oxygen free radical formation are not well known. OBJECTIVES: To investigate whether glyburide, an ATP-regulated potassium (KATP) channel blocker, abolishes isoflurane-induced cardioprotective effects and whether it affects hydroxyl radical formation in the postischemic reperfused heart. ANIMALS AND METHODS: Thirty-nine male Wistar rats were divided into four groups: group C (control, n=10), group I (isoflurane, n=9), group G (glyburide, n=10) and group GI (glyburide and isoflurane, n=10). The hearts were perfused as a Neely’s working heart model. Afterwards, global heart ischemia was induced for 15 min followed by reperfusion for 20 min. The formation of hydroxyl radicals in the coronary effluent and heart was measured with high performance liquid chromatography. RESULTS: Isoflurane alone and glyburide alone produced significant decreases in the duration of ventricular fibrillation during reperfusion (group C 452±345, group I 247±60, group G 261±135 s; P<0.05). In the presence of glyburide, isoflurane did not further decrease the duration of arrhythmia (group GI 230±48 s). Isoflurane reduced hydroxyl radical formation significantly in the coronary effluent during ischemia and reperfusion, but this was prevented by glyburide. CONCLUSION: The results suggest that isoflurane reduces hydroxyl radical formation, at least in part, through activation of KATP channels.

Yamaguchi, Toshiaki; Kashimoto, Satoshi; Oguchi, Takeshi; Kumazawa, Teruo

2002-01-01

252

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.

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

253

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

PubMed Central

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

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

1995-01-01

254

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.

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

2011-01-01

255

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

256

Diallyl disulfide reduced dose-dependently the number of lymphocyte subsets and monocytes in rats.  

PubMed

Diallyl disulfide (DADS) is a major sulfur compound of garlic, and exerts anti-inflammatory, immune-modulatory, and enhancing sympathetic activity effects. However, it still remains unclear how DADS affects the distribution of white blood cell subsets, which is essential to execute effective immune responses and partially regulated by adrenal glucocorticoids. Therefore, we examined the dose-dependent effects of DADS administration on the circulating number of white blood cells (WBCs) and lymphocyte subsets, and plasma corticosterone concentration in rats. Male 10-wk-old Sprague Dawley rats were divided into the DADS-free and DADS-orally administered (dose=10, 20, and 40 mg/kg BW) groups. Blood samples were collected from the tail vein at 0, 1, 2, 4, and 6 h after the administration. DADS administration decreased dose- and time-dependently the circulating number of total WBCs, total lymphocytes, and monocytes. Within the lymphocyte subsets, the circulating number of T-lymphocytes and B-lymphocytes was significantly reduced 4 h after DADS administration in a dose-dependent manner, although that of natural killer (NK) cells was not affected. On the other hand, although DADS administration did not significantly change the circulating number of neutrophils, the circulating number of eosinophils and basophils showed a decreasing tendency after DADS administration. In contrast, plasma corticosterone concentration was increased 2 h after DADS administration in a dose-dependent manner. These results suggest that DADS administration reduces the circulating number of monocytes and lymphocytes, including especially acquired immune cells, via the action of corticosterone, and the effects are induced in a dose-dependent manner. PMID:23132314

Hashizume, Yoko; Shirato, Ken; Abe, Ikumi; Kobayashi, Ayumu; Mitsuhashi, Ryosuke; Shiono, Chikako; Sato, Shogo; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

2012-01-01

257

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

PubMed

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

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

2012-10-16

258

Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia/reperfusion in rats  

PubMed Central

Aims Thrombopoietin (Tpo) is known for its ability to stimulate platelet production. However, it is currently unknown whether Tpo plays a physiological function in the heart. Methods and results We assessed the potential protective role of Tpo in vitro and in vivo in two rat models of myocardial ischaemia/reperfusion. Tpo receptor (c-mpl) message was detected in the heart using RT-PCR, and the Tpo receptor protein was detected using western blotting and immunohistochemistry. Tpo treatment immediately before ischaemia reduced myocardial necrosis, apoptosis, and decline in ventricular function following ischaemia/reperfusion in the rat in a concentration- and dose-dependent manner with an optimal concentration of 1.0 ng/mL in vitro and an optimal dose of 0.05 ?g/kg iv in vivo. Tpo also reduced infarct size when given after the onset of ischaemia or at reperfusion. Tpo activated JAK-2 (Janus kinase-2) and p44 MAPK (mitogen-activated protein kinase) during reperfusion but not prior to ischaemia. Inhibition of JAK-2 (AG-490), p42/44 MAPK (PD98059), mitochondrial KATP channels (5-HD), and sarcolemmal KATP channels (HMR 1098) abolished Tpo-induced resistance to injury from myocardial ischaemia/reperfusion. AG-490, PD98059, 5-HD, and HMR1098 alone had no effect on cardioprotection. Treatment with a single dose of Tpo (0.05 or 1.0 ?g/kg iv) did not result in the elevation of platelet count or haematocrit over a 16-day period. Conclusion A single treatment of Tpo confers cardioprotection through JAK-2, p42/44 MAPK, and KATP channels, suggesting a potential therapeutic role of Tpo in the treatment of injury resulting from myocardial ischaemia and reperfusion.

Baker, John E.; Su, Jidong; Hsu, Anna; Shi, Yang; Zhao, Ming; Strande, Jennifer L.; Fu, Xiangping; Xu, Hao; Eis, Annie; Komorowski, Richard; Jensen, Eric S.; Tweddell, James S.; Rafiee, Parvaneh; Gross, Garrett J.

2010-01-01

259

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.

de Paoli, Frank Vincenzo; ?rtenblad, Niels; Pedersen, Thomas Holm; J?rgensen, Rasmus; Nielsen, Ole Baekgaard

2010-01-01

260

Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.  

PubMed

Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension. PMID:16293589

Belugin, Sergei; Mifflin, Steve

2005-12-01

261

Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats.  

PubMed

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation. PMID:15647340

Bushinsky, David A; Asplin, John R

2005-01-12

262

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

PubMed

Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4, or 8 ?g IFNT/kg body weight (BW) per day (n = 6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose, and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, as well as leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 ?g IFNT/kg BW/day in comparison with control rats. Treatment with 8 ?g IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared with control rats. Oral administration of 8 µg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver, and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals. © 2013 BioFactors 39(5):552-563, 2013. PMID:23804503

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

2013-06-27

263

Rho kinase inhibitors reduce neurally evoked contraction of the rat tail artery in vitro  

PubMed Central

The effects of Rho kinase inhibitors (Y27632, HA-1077) on contractions to electrical stimulation and to application of phenylephrine, clonidine or ?,?-methylene adenosine 5?-triphosphate (?,?-mATP) were investigated in rat tail artery in vitro. In addition, continuous amperometry and intracellular recording were used to monitor the effects of Y27632 on noradrenaline (NA) release and postjunctional electrical activity, respectively. Y27632 (0.5 and 1??M) and HA-1077 (5??M) reduced neurally evoked contractions. In contrast, the protein kinase C inhibitor, Ro31-8220 (1??M), had little effect on neurally evoked contraction. In the absence and the presence of Y27632 (0.5??M), the reduction of neurally evoked contraction produced by the ?-adrenoceptor antagonists prazosin (10?nM) and idazoxan (0.1??M) was similar. The P2-purinoceptor antagonist, suramin (0.1?mM), had no inhibitory effect on neurally evoked contraction in the absence or the presence of Y27632 (1??M). In the presence of Y27632, desensitization of P2X-purinoceptors with ?,?-mATP (10??M) increased neurally evoked contractions. Y27632 (1??M) and H-1077 (5??M) reduced sensitivity to phenylephrine and clonidine. In addition, Y27632 reduced contractions to ?,?-mATP (10??M). Y27632 (1??M) had no effect on the NA-induced oxidation currents or the purinergic excitatory junction potentials and NA-induced slow depolarizations evoked by electrical stimulation. Rho kinase inhibitors reduce sympathetic nerve-mediated contractions of the tail artery. This effect is mediated at a postjunctional site, most likely by inhibition of Rho kinase-mediated ‘Ca2+ sensitization' of the contractile apparatus.

Yeoh, Melanie; Brock, James A

2005-01-01

264

IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia.  

PubMed

Pro-inflammatory cytokines and nitric oxide (NO) are considered responsible for exacerbating brain injury. Activated microglia produce these potentially cytotoxic factors during neuron destruction. The beneficial effects of hypothermia on neuroprotection are considered to be due, in part, to suppression of post-injury inflammatory factors by microglia. However, the underlying mechanisms remain unclear. In particular, the hypothermia's role in modulating anti-inflammatory cytokines is unknown. We examined whether altering culture temperature modifies microglial production of cytokines and NO. Microglia isolated from neonatal rats were cultured with 1 microg/mL lipopolysaccharide (LPS) under hypothermic, normothermic, and hyperthermic conditions for 72 h. Interleukin (IL)-6 and IL-10 levels in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). NO production was analyzed by colorimetric assay of nitrite accumulated in the medium. Compared to normothermia, hypothermia decreased LPS-induced IL-6 production at 6 h of culture. In contrast, hyperthermia reduced IL-6 production throughout culture. IL-10 production was reduced by hypothermia but augmented by hyperthermia at 24-72 h. NO production was reduced by hypothermia throughout culture, while no significant differences in NO production were observed between normothermia and hyperthermia. In this study, hypothermia reduced production of IL-6, IL-10, and NO by LPS-activated microglia, suggesting that the neuroprotective effects of hypothermia might involve not only the inhibition of inflammatory factors, but also anti-inflammatory factor(s). Hyperthermia specifically increased IL-10 production in these cells. These temperature-dependent changes in IL-10 production may imply an important clinical marker for this cytokine in hypothermia-related neuronal protection and in hyperthermia-related neuronal injury. PMID:18533891

Matsui, Tomohiro; Kakeda, Takahiro

2008-06-01

265

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

PubMed Central

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

Masri, Abeer A Al; Eter, Eman El

2012-01-01

266

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

SciTech Connect

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

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

2007-11-03

267

Exposure to a novel stimulus reduces anxiety level in adult and aging rats  

Microsoft Academic Search

Male Wistar rats aged 3, 15 and 24 months were isolated and housed individually for 72 h prior to being subjected to inanimate objects (two objects per rat, each 1.5 cm in diameter and 4 cm in length, made of surgical gauze). Following the exposure to the objects, rats were subsequently tested in an elevated plus-maze. The inanimate objects induced

Madeha Darwish; L. Korányi; C. Nyakas; O. F. X. Almeida

2001-01-01

268

Mesencephalic astrocyte-derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats.  

PubMed

Mesencephalic astrocyte-derived neurotrophic factor (MANF), also known as arginine-rich, mutated in early stage of tumors (ARMET), is a secreted protein that reduces endoplasmic reticulum (ER) stress. Previous studies have shown that MANF mRNA expression and protein levels are increased in the cerebral cortex after brain ischemia, a condition that induces ER stress. The function of MANF during brain ischemia is still not known. The purpose of this study was to examine the protective effect of MANF after ischemic brain injury. Recombinant human MANF was administrated locally to the cerebral cortex before a 60-min middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium chloride (TTC) staining indicated that pretreatment with MANF significantly reduced the volume of infarction at 2 days after MCAo. MANF also attenuated TUNEL labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex. PMID:19399876

Airavaara, Mikko; Shen, Hui; Kuo, Chi-Chung; Peränen, Johan; Saarma, Mart; Hoffer, Barry; Wang, Yun

2009-07-01

269

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

PubMed Central

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

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

2009-01-01

270

Influence of Muscle-Tendon Wrapping on Calculations of Joint Reaction Forces in the Equine Distal Forelimb  

PubMed Central

The equine distal forelimb is a common location of injuries related to mechanical overload. In this study, a two-dimensional model of the musculoskeletal system of the region was developed and applied to kinematic and kinetic data from walking and trotting horses. The forces in major tendons and joint reaction forces were calculated. The components of the joint reaction forces caused by wrapping of tendons around sesamoid bones were found to be of similar magnitude to the reaction forces between the long bones at each joint. This finding highlighted the importance of taking into account muscle-tendon wrapping when evaluating joint loading in the equine distal forelimb.

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

2008-01-01

271

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

PubMed

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

Baier, David B; Gatesy, Stephen M

2013-09-15

272

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

PubMed Central

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

Qui, Guang; Spangler, Edward; Wan, Ruiqian; Miller, Marshall; Mattson, Mark; So, Kwi-fok; de Cabo, Rafael; Zou, Sige; Ingram, Donald

2012-01-01

273

Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats.  

PubMed

The consumption of soy protein was shown to reduce blood lipids in humans and other animal species. Furthermore, it was shown that the ingestion of soy protein maintains normal insulinemia. Thus, the purpose of the present study was to determine whether soy protein affects the synthesis of lipids in the liver through sterol-regulatory element binding protein-1 (SREBP-1) due to modulation of insulin levels. We first conducted a short-term study in which rats were fed a diet containing 18 g/100 g soy protein or casein for 10 d. Rats fed soy protein had significantly lower serum insulin concentrations than rats fed casein, and this response was accompanied by an elevation in hepatic SREBP-1 mRNA that was 53% lower than that in rats fed casein at d 10. The increase in SREBP-1 mRNA occurred 30 min after consumption of the casein mean, and increased steadily for the next 2 h. We then conducted a second study to assess the long-term effect of soy protein consumption for 150 d on hepatic SREBP-1 expression. Long-term consumption of soy protein maintained normal insulin concentrations compared with rats fed casein, which were hyperinsulinemic. Thus, rats fed the soy protein diet had significantly lower expression of SREBP-1 mRNA than rats fed the casein diet. Soy protein intake also reduced the expression of fatty acid synthase (FAS) and malic enzyme, leading to low hepatic lipid depots of triglycerides and cholesterol, whereas rats fed the casein diet developed fatty liver. These data suggest that soy protein regulates SREBP-1 expression by modulating serum insulin concentration, thus preventing the development of fatty liver. PMID:14988441

Ascencio, Claudia; Torres, Nimbe; Isoard-Acosta, Fernando; Gómez-Pérez, Francisco J; Hernández-Pando, Rogelio; Tovar, Armando R

2004-03-01

274

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

2013-05-07

275

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

2010-04-08

276

Activity-based anorexia is associated with reduced hippocampal cell proliferation in adolescent female rats.  

PubMed

Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics core features of the clinical psychiatric disorder, including severe food restriction, weight loss, and hyperactivity. The ABA model is currently being used to study starvation-induced changes in the brain. Here, we examined hippocampal cell proliferation in animals with ABA (or the appropriate control conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups: control (24h/day food access), food-restricted (1h/day food access), exercise (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was injected and the rats were perfused 2h later. Brains were removed and subsequently processed for BrdU and Ki67 immunohistochemistry. The acute induction of ABA reduced cell proliferation in the dentate gyrus. This effect was significant in the hilus region of the dentate gyrus, but not in the subgranular zone, where adult neurogenesis occurs. Marked decreases in cell proliferation were also observed in the surrounding dorsal hippocampus and in the corpus callosum. These results indicate a primary effect on gliogenesis rather than neurogenesis following 3 days of ABA. For each brain region studied (except SGZ), there was a strong positive correlation between the level of cell proliferation and body weight/food intake. Future studies should examine whether these changes are maintained following long-term weight restoration and whether alterations in neurogenesis occur following longer exposures to ABA. PMID:22981561

Barbarich-Marsteller, Nicole C; Fornal, Casimir A; Takase, Luiz F; Bocarsly, Miriam E; Arner, Candice; Walsh, B Timothy; Hoebel, Bartley G; Jacobs, Barry L

2012-09-04

277

Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury*  

PubMed Central

Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Methods: Experiments were conducted in male Sprague-Dawley rats (n=78) weighing 300~400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h, 24 h or continuously, followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site, rostral site and caudal site (7.5 mm away from the lesion). Results: The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day 1, and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression, compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2 (Bcl-2)-associated X-protein (Bax), but not to Bcl-2, correlated with those of TUNEL-positive cells. Conclusion: Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.

Xu, Kan; Chen, Qi-xin; Li, Fang-cai; Chen, Wei-shan; Lin, Min; Wu, Qiong-hua

2009-01-01

278

Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats.  

PubMed

Exercise can exert beneficial effects on cognitive functions of older subjects and it can also play an important role in the prevention of neurodegenerative diseases. At the same time it is perceivable that limited information is available on the nature of molecular pathways supporting the antioxidant effects of exercise in the brain. In this study 12-month old, middle-aged female Wistar rats were subjected to daily moderate intensity exercise on a rodent treadmill for a period of 15weeks which covered the early aging period unmasking already some aging-related molecular disturbances. The levels of reactive oxygen species (ROS), the amount of protein carbonyls, the levels of antioxidant intracellular enzymes superoxide dismutases (SOD-1, SOD-2) and glutathione peroxidase (GPx) were determined in the hippocampus. In addition, to identify the molecular pathways that may be involved in ROS metabolism and mitochondrial biogenesis, the activation of 5'-AMP-activated protein kinase (AMPK), the protein level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (mtTFA) were measured. Our results revealed a lower level of ROS associated with a reduced amount of protein carbonyls in the hippocampus of physically trained rats compared to sedentary controls. Furthermore, exercise induced an up-regulation of SOD-1 and GPx enzymes, p-AMPK and PGC-1?, that can be related to an improved redox balance in the hippocampus. These results suggest that long-term physical exercise can comprises antioxidant properties and by this way protect neurons against oxidative stress at the early stage of aging. PMID:22982624

Marosi, K; Bori, Z; Hart, N; Sárga, L; Koltai, E; Radák, Z; Nyakas, C

2012-09-12

279

Bortezomib Reduces Neointimal Hyperplasia in a Rat Carotid Artery Injury Model  

PubMed Central

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

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

2013-01-01

280

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

PubMed

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

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

2013-05-27

281

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

PubMed Central

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

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

2012-01-01

282

Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion.  

PubMed

Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic/cataplerotic pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic/cataplerotic enzymes content. Male Wistar rats were randomly assigned to one of the four experimental groups as follows: control sedentary group (CTL), trained 1 day per week (TRE1×), trained 3 days per week (TRE3×) and trained 5 days per week (TRE5x) and submitted to an 8 weeks endurance-training protocol. After the training protocol, pancreatic islets were isolated and incubated with basal (2.8 mM) and stimulating (16.7 mM) glucose concentrations for GSIS measurement by radioimmunoassay. In addition, pyruvate carboxylase (PYC), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), ATP-citrate lyase (ACL) and glutamate dehydrogenase (GDH) content were quantified by western blotting. Our data showed that 8 weeks of chronic endurance exercise reduced GSIS by 50% in a dose-response manner according to weekly exercise frequency. PYC showed significant twofold increase in TRE3×. PYC enhancement was even higher in TRE5× (p < 0.0001). PDH and PDK4 reached significant 25 and 50% enhancement, respectively compared with CTL. ACL and GDH also reported significant 50 and 75% increase, respectively. The absence of exercise-induced correlations among GSIS and anaplerotic/cataplerotic enzymes suggests that exercise may control insulin release by activating other signaling pathways. The observed anaplerotic and cataplerotic enzymes enhancement might be related to ?-cell surviving rather than insulin secretion. PMID:21287194

Zoppi, Claudio C; Calegari, Vivian C; Silveira, Leonardo R; Carneiro, Everardo M; Boschero, Antonio C

2011-02-02

283

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

PubMed Central

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

2013-01-01

284

Viscous Dietary Fiber Reduces Adiposity and Plasma Leptin and Increases Muscle Expression of Fat Oxidation Genes in Rats  

Microsoft Academic Search

Dietary interventions that reduce accumulation of body fat are of great interest. Consumption of viscous dietary fibers cause well-known positive metabolic effects, such as reductions in the postprandial glucose and insulin concentrations. However, their effect on body composition and fuel utilization has not been previously studied. To examine this, rats were fed a viscous nonfermentable dietary fiber, hydroxypropyl methylcellulose (HPMC),

Ajmila Islam; Anthony E. Civitarese; Robert L. Hesslink; Daniel D. Gallaher

2012-01-01

285

Targeted Over-Expression of Glutamate Transporter 1 (GLT-1) Reduces Ischemic Brain Injury in a Rat Model of Stroke  

Microsoft Academic Search

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV)

Brandon K. Harvey; Mikko Airavaara; Jason Hinzman; Emily M. Wires; Matthew J. Chiocco; Douglas B. Howard; Hui Shen; Greg Gerhardt; Barry J. Hoffer; Yun Wang

2011-01-01

286

Stimulus Preexposure Reduces Generalization of Conditioned Taste Aversions Between Alcohol and Non-Alcohol Flavors in Infant Rats  

Microsoft Academic Search

Results of 3 experiments showed that infant rats (age 13–17 days) generalize conditioned taste aversions between alcohol and non-alcohol tastes such as a mixture of sucrose and quinine, apple cider vinegar, or coffee. Nonreinforced preexposure to those tastes reduced generalized aversions between them. Generalization between alcohol and sucrose-quinine was reduced not only after preexposure to both tastes, but also when

M. Gabriela Chotro; Gumersinda Alonso

2003-01-01

287

Ethyl pyruvate reduces myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats  

Microsoft Academic Search

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I\\/R) injury. Ethyl\\u000a pyruvate (EP), a potent reactive oxygen species scavenger, has been reported to inhibit myocardial apoptosis and reduce myocardial\\u000a I\\/R injury. The aim of this study was to investigate the mechanism by which EP reduces myocardial I\\/R injury in rats. Anesthetized\\u000a male

Xiaorong Hu; Bo Cui; Xiaoya Zhou; Changwu Xu; Zhibing Lu; Hong Jiang

288

Augmenting and Reducing of Visual Evoked Potentials in High and Low-Sensation Seeking Humans, Cats, and Rats  

Microsoft Academic Search

High- and low-sensation seeking behaviors in human and cat are shown to be correlated with visual evoked potential (VEP) augmenting and reducing, respectively. Demonstration of this relationship in RHA\\/Verh and RLA\\/Verh rats provides a heuristic animal model with which to investigate the physiological and genetic basis of this relationship. Recent work is described which shows that VEP augmenting and reducing

Jerome Siegel

1997-01-01

289

Dietary restriction reduces hepatocyte proliferation and enhances p53 expression but does not increase apoptosis in normal rats during development  

Microsoft Academic Search

Dietary restriction (DR) retards physical growth, resulting in small body size, reduced liver weight and reduced number of hepatocytes in rats. We examined the effects of DR on proliferation and apoptosis of hepatocytes during development and explained these changes subcellularly using immunohistochemistry for bromodeoxyuridine (BrdU) incorporation, proliferating cell nuclear antigen (PCNA) and p53, terminal dUTP nick end labeling (TUNEL) and

Yoshikazu Higami; Isao Shimokawa; Kohei Ando; Kenji Tanaka; Tomoshi Tsuchiya

2000-01-01

290

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

PubMed

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

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

2009-03-01

291

Long-term caloric restriction reduces metabolic rate and heart rate under cool and thermoneutral conditions in FBNF1 rats.  

PubMed

The long-term metabolic and cardiovascular responses to caloric restriction (CR) are poorly understood. We examined the responses to one year of CR in FBNF1 rats housed in cool (COOL; T(a)=15 °C) or thermoneutral (TMN; T(a)=30 °C) conditions. Rats were acclimated to COOL or TMN for 2 months, instrumented for cardiovascular telemetry and studied in calorimeters. Baseline caloric intake, oxygen consumption (VO(2)), mean arterial blood pressure (MAP), and heart rate (HR) were determined prior to assignment to ad lib (AL) or CR groups (30-40% CR) within each T(a) (n = 8). Groups of rats were studied after 10 weeks CR, one year CR, and after 4 days of re-feeding. Both 10 weeks and one year of CR reduced HR and VO(2) irrespective of T(a). Evaluation of the relationship between metabolic organ mass (liver, heart, brain, and kidney mass) and energy expenditure revealed a clear shift induced by CR to reduce expenditure per unit metabolic mass in both COOL and TMN groups. Re-feeding resulted in prompt elevations of HR and VO(2) to levels observed in control rats. These findings are consistent with the hypothesis that long term CR produces sustained reductions in metabolic rate and heart rate in rats. PMID:21513729

Knight, W David; Witte, M M; Parsons, A D; Gierach, M; Overton, J Michael

2011-04-12

292

Cholecystokinin reduces sucrose palatability in rats: evidence in support of a satiety effect.  

PubMed

To investigate the hypothesis that peripherally administered cholecystokinin (CCK) reduces food intake by the production of aversive internal cues, we examined the effects of the sulfated, octapeptide form of CCK on taste reactivity responses to oral sucrose infusions in male rats implanted with intraoral cannulas. After injection of CCK (4, 8, or 16 micrograms/kg ip) or 0.15 M saline (1 ml/kg ip), a series of brief (30 s) intraoral infusions of a 0.30 M sucrose solution was administered at 2-min intervals for 10 min. All doses of CCK were found to significantly decrease ingestive responding during the first and subsequent sucrose infusions without promoting a significant increase in aversive responses relative to controls. The lack of a gradual, conditioned shift in taste reactivity responses, from an ingestive to an aversive pattern (which is typically observed after LiCl administration), suggests that the production of nausea-like aversive internal cues was likely not responsible for the observed CCK-induced alterations in taste reactivity responses. It appears that the unconditioned, satiogenic effects of CCK contributed to the selective reduction in ingestive responses observed in the present study. PMID:7810758

Eckel, L A; Ossenkopp, K P

1994-12-01

293

Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats.  

PubMed

An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts, rich in omega fatty acids, have been shown to improve memory, cognition and neuronal effects related to oxidative stress (OS) and inflammation (INF) in animals and human trials. The current study found that feeding 19-month-old rats with a 6% or 9% walnut diet significantly reduced the aggregation of polyubiquitinated proteins and activated autophagy, a neuronal housekeeping function, in the striatum and hippocampus. Walnut-fed animals exhibited up-regulation of autophagy through inhibiting phosphorylation of mTOR, up-regulating ATG7 and Beclin 1, and turnover of MAP1BLC3 proteins. The clearance of polyubiquitinated protein aggregates such as p62/SQSTM1 was more profound in hippocampus, a critical region in the brain involved in memory and cognitive performance, than striatum. The clearance of ubiquitinated aggregates was in tandem with significant reductions in OS/INF, as indicated by the levels of P38-MAP kinase and phosphorylations of nuclear factor kappa B and cyclic AMP response element binding protein. The results demonstrate the effectiveness of a walnut-supplemented diet in activating the autophagy function in brain beyond its traditionally known antioxidant and anti-inflammatory benefits. PMID:22917841

Poulose, Shibu M; Bielinski, Donna F; Shukitt-Hale, Barbara

2012-08-20

294

Agmatine Reduces Balance Deficits In a Rat Model Of Third Trimester Binge-Like Ethanol Exposure  

PubMed Central

This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1–8 or PND 8–15. On PND 31–33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1–8 exposure period. ETOH exposure during the 2nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption.

Lewis, B.; Wellman, K.A.; Barron, S.

2007-01-01

295

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

PubMed

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

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

2012-09-11

296

Reduced expression of complexins I and II in rats bred for learned helplessness.  

PubMed

Disturbed synaptic transmission contributes to the pathophysiology of mood disorders. Post mortem studies reported reduced expression of the synaptic vesicle protein (SVP) complexins I and II in depression. Antidepressants were found to induce the expression of these genes. Since animals with congenital susceptibility to learned helplessness provide a valid animal model of depression, we investigated the expression of different SVPs in this system by semiquantitative in situ hybridization. Rats bred for congenital learned helpless behavior (cLH, N=6) failed to interrupt foot shock currents by lever pressing (mean 12.3 failures out of 15 trials). These animals showed significantly lower expression of complexins I and II mRNA in hippocampal, limbic and cortical brain areas compared to not helpless animals (cNLH, N=6) with a mean failure rate of 0.83 out of 15 trials. Expression levels of complexins I and II significantly correlated with the failure rate in the test paradigm. In contrast, the expressions of synaptotagmin I and synaptophysin were found unchanged. This investigation provides a further validation of the LH model of depression. The experimental data fit well into current pathogenetic concepts of mood disorders and support the hypothesis, that complexins are pivotal players in the pathophysiology of depression and tentative targets of antidepressants. PMID:17320830

Zink, Mathias; Vollmayr, Barbara; Gebicke-Haerter, Peter J; Henn, Fritz A; Thome, Johannes

2007-01-26

297

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

PubMed

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

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

2012-12-01

298

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

PubMed Central

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

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

2013-01-01

299

High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats  

Microsoft Academic Search

The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m\\/day. Calcium supplementation was instituted

Kirsimarja Sallinen; Pertti Arvola; Heikki Wuorela; Heikki Ruskoaho; Heikki Vapaatalo; Ilkka Pörsti

1996-01-01

300

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

Microsoft Academic Search

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

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

2007-01-01

301

Treadmill exercise reduces self-administration of morphine in male rats  

Microsoft Academic Search

Exercise can activate the same pathways as morphine. The aim of the present study was to clarify the effect of short-term and mid-term exercises on the self-administration of morphine in rats. Male Wistar rats were initially trained to receive small pellets of food by pressing the active lever in self-administration apparatus. Rats were divided into 4 groups: Saline, Morphine, Exercise

Mahmoud Hosseini; Hojjat Allah Alaei; Asieh Naderi; Mohammad Reza Sharifi; Reza Zahed

2009-01-01

302

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

Microsoft Academic Search

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

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

1990-01-01

303

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

PubMed Central

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

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

2011-01-01

304

Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats  

PubMed Central

BACKGROUND: Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohn’s disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell/matrix/cytokine and growth factor interactions, but may be a reversible phenomenon. Of the several molecules regulating fibrogenesis, transforming growth factor-beta 1 (TGF-?1) appears to play a pivotal role; it is strongly induced by the local activation of angiotensin II. The levels of both TGF-?1 and angiotensin II are elevated in fibrostenosing Crohn’s disease. AIMS: To evaluate the in vivo effect of losartan – an angiotensin II receptor antagonist – on the course of chronic colitis-associated fibrosis and on TGF-?1 expression. METHODS: Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg/mL) while losartan was administered orally daily by gavage (7 mg/kg/day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-?1 levels was measured using ELISA. RESULTS: Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-?1 concentration. CONCLUSIONS: Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-?1 expression.

Wengrower, Dov; Zanninelli, Giuliana; Latella, Giovanni; Necozione, Stefano; Metanes, Issa; Israeli, Eran; Lysy, Joseph; Pines, Mark; Papo, Orit; Goldin, Eran

2012-01-01

305

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

PubMed Central

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

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

2008-01-01

306

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.

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

2007-01-01

307

Contractile properties of single motor units in two multi-tendoned muscles of the cat distal forelimb  

Microsoft Academic Search

The contractile properties of motor units (MUs) in two multi-tendoned forelimb muscles were investigated. In anesthetized cats single MUs of the extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) muscles were selectively activated by stimulation of cervical ventral root filaments. MUs were characterized by various tests including single twitches, series of tetanic contractions providing a tension-frequency relation and a

N. Fritz; C. Schmidt

1992-01-01

308

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

Microsoft Academic Search

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

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

1992-01-01

309

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

Microsoft Academic Search

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

J. H. Martin

1996-01-01

310

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

Microsoft Academic Search

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

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

2007-01-01

311

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

Microsoft Academic Search

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

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

1968-01-01

312

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

Microsoft Academic Search

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

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

1968-01-01

313

Hypoxic preconditioning confers long-term reduction of brain injury and improvement of neurological ability in immature rats.  

PubMed

Exposure to preconditioning (PC) hypoxia 24 h before a severe hypoxic-ischemic (HI) insult reduces development of injury in the immature brain. Several protective regimens have proved effective in the short-term but not in the long-term perspective. The aim of the present study, therefore, was to evaluate the PC effect on long-term morphologic and neurologic outcome in the developing brain. Six-day-old rats were subjected to hypoxia (36 degrees C, 8.0% O2; PC/HI group) and sham controls to normoxia (36 degrees C; HI group) for 3 h. Twenty-four hours later, all rats were exposed to cerebral HI produced by unilateral carotid artery occlusion combined with 1 h, 15 min of hypoxia (36 degrees C, 7.7% O2). A cylinder test was used to evaluate forelimb asymmetry to determine sensorimotor function at 4, 6, and 8 wk of age. Spatial/cognitive ability was assessed by Morris water maze trials at 7 wk of recovery. Neuropathologic analysis was performed 8 wk after insult. Brain damage was reduced (p<0.0001) in PC/HI (45.0+/-11.1 mm3) in comparison with HI (159.3+/-12.2 mm3) rats. A bias for using the ipsilateral forelimb in wall movements was observed in the cylinder test in HI compared with PC/HI rats at 4 (p<0.001), 6 (p<0.01), and 8 (p<0.0001) wk of age. Results of the Morris water maze test revealed differences (p<0.0001) in average path length between groups on the third and fourth day of trials. Hypoxic PC before HI reduced brain injury by 72% at 8 wk after the insult and provided long-term improvement of sensorimotor and spatial/cognitive functions. PMID:15611346

Gustavsson, Malin; Anderson, Michelle F; Mallard, Carina; Hagberg, Henrik

2004-12-20

314

Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.  

PubMed

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0mm depth, 4.0m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI. PMID:23770071

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-06-13

315

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

Microsoft Academic Search

We investigated on the mechanism responsible for the reduced ATP-sensitive K+(KATP) channel activity recorded from skeletal muscle of K+-depleted rats. Patch-clamp and gene expression measurements of KATP channel subunits were performed. A down-regulation of the KATP channel subunits Kir6.2(?70%) and SUR2A(?46%) in skeletal muscles of K+-depleted rats but no changes in the expression of Kir6.1, SUR1 and SUR2B subunits were

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

2008-01-01

316

Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-? pathway in experimental autoimmune encephalomyelitis in rats.  

PubMed

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases. In our previous studies, we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we further investigated the mechanisms of sinomenine treatment in EAE rats. In EAE rats, treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS) effect, which is related to the reductions of Th1 cytokine interferon-? (IFN-?) and its transcription factor, T-bet, in spinal cords. Moreover, sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-? in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes. However, sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-? and tumor necrosis factor ? in vitro. In conclusion, the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-? pathway. PMID:23554784

Gu, Bingjie; Zeng, Yanying; Yin, Cheng; Wang, Huijiuan; Yang, Xiaofan; Wang, Song; Ji, Xiaohui

2012-06-30

317

Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-? pathway in experimental autoimmune encephalomyelitis in rats  

PubMed Central

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases. In our previous studies, we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we further investigated the mechanisms of sinomenine treatment in EAE rats. In EAE rats, treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS) effect, which is related to the reductions of Th1 cytokine interferon-? (IFN-?) and its transcription factor, T-bet, in spinal cords. Moreover, sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-? in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes. However, sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-? and tumor necrosis factor ? in vitro. In conclusion, the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-? pathway.

Gu, Bingjie; Zeng, Yanying; Yin, Cheng; Wang, Huijiuan; Yang, Xiaofan; Wang, Song; Ji, Xiaohui

2012-01-01

318

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

PubMed Central

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

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

2008-01-01

319

Stimulus preexposure reduces generalization of conditioned taste aversions between alcohol and non-alcohol flavors in infant rats.  

PubMed

Results of 3 experiments showed that infant rats (age 13-17 days) generalize conditioned taste aversions between alcohol and non-alcohol tastes such as a mixture of sucrose and quinine, apple cider vinegar, or coffee. Nonreinforced preexposure to those tastes reduced generalized aversions between them. Generalization between alcohol and sucrose-quinine was reduced not only after preexposure to both tastes, but also when only the nonconditioned taste was preexposed, whereas with alcohol and vinegar, both tastes had to be preexposed to obtain that effect. In no case was generalization reduced when only the to-be-conditioned taste was preexposed. Previous experience with alcohol alone, as well as with similar gustatory stimuli, may enhance subjects' ability to differentiate them during infantile stages in rats. PMID:12619914

Chotro, M Gabriela; Alonso, Gumersinda

2003-02-01

320

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

PubMed Central

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

O'Brien, Emmanuelle Simon; Legastelois, Remi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stephanie; Pierrefiche, Olivier; Andre, Etienne; Naassila, Mickael

2011-01-01

321

Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction  

PubMed Central

Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dysfunction.We examined whether diabetes-induced reductions in sciatic nerve conduction velocity and EBF were associated with impaired endothelium-dependent dilation in adjacent arterioles. We measured motor nerve conduction velocity (MNCV) in the sciatic nerve using a non-invasive procedure, and sciatic nerve nutritive blood flow using microelectrode polarography and hydrogen clearance. In vitro videomicroscopy was used to quantify arteriolar diameter responses to dilator agonists in arterioles overlying the sciatic nerve.MNCV and EBF in 4-week-STZ-induced diabetic rats were decreased by 22% and 49% respectively. Arterioles were constricted with U46619 and dilation to acetylcholine (ACh), aprikalim, or sodium nitroprusside (SNP) examined. All agonists elicited dose-dependent dilation in control and diabetic rats, although ACh-induced dilation was significantly reduced in diabetic rats. Treating vessels from normal or diabetic rats with indomethacin (INDO) alone did not significantly affect ACh-induced relaxation. However, ACh-induced vasodilation was significantly reduced by treatment with KCl or N?-nitro-L-arginine (LNNA) alone. Combining LNNA and KCl further reduced ACh-induced dilation in these vessels.Diabetes causes vasodilator dysfunction in a microvascular bed that provides circulation to the sciatic nerve. These studies imply that ACh-induced dilation in these vessels is mediated by multiple mechanisms that may include the endothelial-dependent production of nitric oxide and endothelial-derived hyperpolarizing factor. This impaired vascular response is associated with neural dysfunction.

Terata, K; Coppey, L J; Davidson, E P; Dunlap, J A; Gutterman, D D; Yorek, M A

1999-01-01

322

Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats.  

PubMed

Both Moutan cortex of Paeonia suffruticosa Andrews (MC) and the root of Paeonia lactiflora Pall (PL) are important Traditional Chinese herbs used commonly to treat inflammatory and pyretic disorders. Paeonol, a common component of MC causes anti-platelet aggregation and scavenges free radicals. Therefore, the aim of the present study is to investigate the effects of Paeonol on cerebral infarct. A total of 60 male Sprague-Dawley (SD) rats were studied. An animal model of cerebral infarct was established by occluding both common carotid arteries and the right middle cerebral artery for 90 min, followed by a 24 h period of reperfusion. The percentage of cerebral infarction area to total brain area in each piece of brain tissue, and neuro-deficit score were measured. Superoxide anion was determined by the number of lucigenin-chemiluminescence (CL) counts. ED1 (mouse anti rat CD68) and interleukin-1beta (IL-1beta) immunostaining in the cerebral infarction region were also investigated for activation of microglia. The results indicated that Paeonol 15 and 20 mg/kg pretreatment and 20 mg posttreatment reduced the cerebral infarction area; Paeonol 15 and 20 mg/kg pretreatment reduced the neuro-deficit score. In addition, Paeonol 20 mg/kg pretreatment reduced the lucigenin-CL counts at 2 h period of reperfusion. The number of ED1 and IL-1beta immunoreactive cells also reduced in the cerebral infarction region; there were no significant changes in blood sugar levels. The results show that Paeonol reduced cerebral infarct and neuro-deficit in rat, suggesting Paeonol might play a similar role in reducing cerebral infarction in humans. Paeonol suppresses and scavenges superoxide anion, and inhibit microglia activation and IL-1beta in ischemia-reperfusion injured rats. PMID:16458462

Hsieh, Ching-Liang; Cheng, Chin-Yi; Tsai, Tung-Hu; Lin, I-hsin; Liu, Chung-Hsiang; Chiang, Su-Yin; Lin, Jaung-Geng; Lao, Chih-Jui; Tang, Nou-Ying

2006-02-03

323

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

PubMed Central

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

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

2010-01-01

324

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

PubMed

In a recent study Diogo & Abdala [(2007) J Morphol 268, 504-517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans. PMID:19438764

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

2009-05-01

325

Reduced glutathione regenerating enzymes undergo developmental decline and sexual dimorphism in the rat cerebral cortex  

Microsoft Academic Search

Oxidative stress during development may predispose humans to neurodegenerative disorders in old age. Moreover, numerous ailments of brain disproportionately affect one of the genders. We therefore hypothesized that, activities of enzymes regenerating and utilizing glutathione (GSH) show sexual dimorphism and developmental differences in rat brain. To test this hypothesis, we collected cortex tissue from male and female Sprague–Dawley rats at

Vikas V. Dukhande; Alfred O. Isaac; Tanushree Chatterji; James C. K. Lai

2009-01-01

326

Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol  

Microsoft Academic Search

Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report

Xue-Min Gao; Kazuo Sakai; Carol A Tamminga

1998-01-01

327

DIETARY SATURATED FAT REDUCES ALCOHOLIC HEPATOTOXICITY IN RATS BY ALTERING FATTY ACID METABOLISM AND MEMBRANE COMPOSITION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Rats fed a saturated fat diet are protected from experimentally induced alcoholic liver disease, but the molecular mechanisms underlying this phenomenon remain in dispute. We fed male Sprague-Dawley rats intragastrically by total enteral nutrition using diets with or without ethanol. In 1 control an...

328

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats  

Microsoft Academic Search

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our

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

2007-01-01

329

Musculotopic organization of the motor neurons supplying forelimb and shoulder girdle muscles in the mouse.  

PubMed

We identified the motor neurons (MNs) supplying the shoulder girdle and forelimb muscles in the C57BL/6J mouse spinal cord using Fluoro-Gold retrograde tracer injections. In spinal cord transverse sections from C2 to T2, we observed two MN columns (medial and lateral) both with ventral and dorsal subdivisions. The dorsolateral column consisted of the biceps brachii, forearm extensors, forearm flexors, and hand MNs, and the ventrolateral column consisted of the latissimus dorsi, trapezius, teres major, deltoid, and triceps MNs. The supraspinatus muscle MNs were located in the dorsomedial column, and pectoralis major and serratus anterior MNs were located in the ventromedial columns. MNs of the dorsolateral column innervated the biceps brachii in mid-C4 to mid-C7, forearm extensors in caudal C4 to mid-T1, forearm flexors in rostral C5 to mid-T1, and hand muscles in mid-C8 to mid-T2 segments. The MNs innervating the trapezius were located in mid-C2 to mid-C4, triceps brachii in mid-C6 to rostral T1, deltoid in rostral C4 to mid-C6, teres major in rostral C5 to mid-C8, and latissimus dorsi in mid-C5 to caudal C8. In addition, MNs innervating the supraspinatus were located from rostral C4 to caudal C8, pectoralis major in mid-C6 to mid-T2, and serratus anterior in rostral C5 to caudal C7/rostral C8 segments. While the musculotopic pattern of MN groups was very similar to that documented for other species, we found differences in the position and cranio-caudal extent of some MN pools compared with previous reports. The identification of mouse forelimb MNs can serve as an anatomical reference for studying degenerative MN diseases, spinal cord injury, and developmental gene expression. PMID:22362202

Bácskai, Tímea; Fu, Yuhong; Sengul, Gulgun; Rusznák, Zoltán; Paxinos, George; Watson, Charles

2012-02-24

330

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys  

PubMed Central

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

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

2012-01-01

331

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.

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

332

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

PubMed

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

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

2012-06-02

333

Immediate constraint-induced movement therapy causes local hyperthermia that exacerbates cerebral cortical injury in rats  

Microsoft Academic Search

Constraint-induced movement therapy (CIMT), which involves restraint of the nonimpaired arm coupled with physiotherapy for the impaired arm, lessens impairment and disability in stroke patients. Surprisingly, immediate ipsilateral forelimb immobilization exacerbates brain injury in rats. We tested whether immediate ipsilateral restraint for 7 days aggravates injury after a devascularization lesion in rats. Furthermore, we hypothesized that ipsilateral restraint aggravates injury

Suzanne B. DeBow; John E. McKenna; Bryan Kolb; Frederick Colbourne

2004-01-01

334

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

PubMed Central

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

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

2010-01-01

335

Deficiency in endothelin receptor B reduces proliferation of neuronal progenitors and increases apoptosis in postnatal rat cerebellum.  

PubMed

Endothelins regulate cellular functions in the mammalian brain through the endothelin receptors A and B (EDNRA and EDNRB). In this study, we investigated the role of EDNRB on cell proliferation in the cerebellum by using the spotting lethal (sl) rat, which carries a naturally occurring deletion in the EDNRB gene. Proliferating cells in the three genotypes, wild-type (+/+), heterozygous (+/sl) and homozygous mutant (sl/sl) rats were labelled by intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) at postnatal day 2. The density of BrdU-positive cells (per mm(2)) in the external germinal layer of sl/sl rats (Mean +/- SEM, 977 +/- 388) was significantly reduced compared to +/+ (4915 +/- 631) and +/sl (2304 +/- 557) rats. Subsequently, we examined the effects of EDNRB mutation on neural apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling assay. This showed that the density of apoptotic cells in the cerebella of sl/sl rats (9.3 +/- 0.5/mm(2)) was significantly more increased than +/+ rats (4 +/- 0.7). The expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured with standard ELISA, but were unchanged in all genotypes. These results suggest that ENDRB mediates neural proliferation and have anti-apoptotic effects in the cerebellum of the postnatal rat, and that these effects are independent of changes in the expression of BDNF and GDNF. Our findings will lead to better understanding of the morphological changes in the cerebellum of Hirschsprung's disease patients with congenital EDNRB mutation. PMID:18683040

Vidovic, Maria; Chen, Ming-Ming; Lu, Qun-Ying; Kalloniatis, Katherine F; Martin, Ben M; Tan, Abel H Y; Lynch, Celina; Croaker, G David H; Cass, Daniel T; Song, Zan-Min

2008-08-06

336

Behavioral characteristics of rats predisposed to learned helplessness: reduced reward sensitivity, increased novelty seeking, and persistent fear memories.  

PubMed

The congenitally helpless rat strain, which was selectively bred for increased susceptibility to learned helplessness, may model the predisposition to affective disorders, including depression and post-traumatic stress disorder. Other than the selected trait, the behavior of this strain is not well characterized. In this study, we assessed congenitally helpless rats on several behavioral tests. First, we assessed reward sensitivity by measuring their consumption of a 5% sucrose solution. Next, we assessed exploratory behavior and fearfulness in both a novel and familiar open field, and in a light-dark test. Finally, we assessed fear conditioning by exposing the animals to 4 tone-shock pairs on 1 day (acquisition) and then presenting 60 tones over the next 2 days (extinction). Compared to normal Sprague-Dawley controls, congenitally helpless rats showed less consumption of the sucrose solution and more exploratory behavior in the novel, but not the familiar, open fields. They also showed less fearfulness in the light-dark test, but more conditioned freezing to the tone predicting shock. Moreover, this freezing was resistant to extinction; congenitally helpless rats not only failed to show a fear decrement during extinction, but actually showed increased fear, a phenomenon termed "paradoxical enhancement." Thus, congenitally helpless rats appear to have a behavioral phenotype characterized by reduced sensitivity to reward, increased drive to explore novel environments, and increased propensity to form and maintain fear-associated memories. This behavioral phenotype is discussed as resembling the personality of humans vulnerable to post-traumatic stress disorder. PMID:16095730

Shumake, Jason; Barrett, Douglas; Gonzalez-Lima, F

2005-11-01

337

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

PubMed

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

2012-06-01

338

Naringenin reduces tumor size and weight lost in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.  

PubMed

Carcinoma of the stomach is reportedly the second most common cancerous condition affecting the general population. Administration of antioxidants is reported to effectively alleviate the risk of gastric carcinoma. Therefore, we assessed the protective role of naringenin, an antioxidant and naturally occurring citrus flavanone, on gastric carcinogenesis induced by MNNG (200 mg/kg body weight) and S-NaCl (1 mL per rat) in Wistar rats (obtained from the Central Animal House Facility, University of Madras, Taramani Campus, Chennai, India). The animals were divided into 5 groups, and the effects of naringenin on simultaneous and posttreated stages of MNNG were tested. Cancer risk was analyzed along with their antioxidant status. The LPO levels in the experimental groups were assessed as an index of oxidative milieu. Altered redox status was subsequently investigated by assaying the superoxide and hydroxyl radicals, the enzymatic antioxidants (SOD, CAT, GPx), and the nonenzymatic antioxidants viz reduced GSH, vitamin C, and vitamin E. In the presence of MNNG, cancer incidence and LPO levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH, Vitamins C, and E) were decreased in the treated rats compared with control rats. Administration of naringenin to gastric carcinoma-induced rats largely up-regulated the redox status to decrease the risk of cancer. We conclude that up-regulation of antioxidants by naringenin treatment might be responsible for the anticancer effect in gastric carcinoma. PMID:19083396

Ekambaram, Ganapathy; Rajendran, Peramaiyan; Magesh, Venkataraman; Sakthisekaran, Dhanapal

2008-02-01

339

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

PubMed

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

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

2013-08-01

340

Prenatal ethanol exposure reduces phosphoinositide hydrolysis stimulated by quisqualate in rat cerebellar granule cell cultures.  

PubMed

Prenatal ethanol exposure-induced alteration in poly-phosphoinositide (PPI) hydrolysis stimulated by excitatory amino acids (EAA) was studied in rat cerebellar granule cells previously labeled with [3H]myoinositol. The prenatal exposure to ethanol was achieved via maternal consumption of a Sustacal (chocolate flavored) liquid diet containing either 5% ethanol (w/v, 35% of calories) or isocaloric sucrose (pair-fed) substituted for ethanol from gestation d 11 until the day of parturition. The ionotropic glutamate receptor agonists, N-methyl-D-aspartate, kainate or (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (100 microM each) induced a two- to four-fold increase in PPI hydrolysis over the basal level, regardless of the liquid dietary treatment. Stimulation with quisqualate (QA), an agonist activating both metabotropic and ionotropic glutamate receptors, resulted in a much stronger and dose-dependent response in PPI hydrolysis and exposure in utero to ethanol significantly reduced this response. Tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or (+/-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) had no effect on QA-stimulated PPI hydrolysis nor on the suppression of this hydrolysis by ethanol. Exposure in utero to ethanol did not affect PPI hydrolysis stimulated by a selective metabotropic glutamate receptor agonist, trans-(+/-)-l-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD). Although the PPI hydrolysis stimulated by t-ACPD could be blocked by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), an antagonist of the metabotropic glutamate receptor, MCPG was incapable of affecting QA-induced PPI hydrolysis and the suppressive effects of prenatal ethanol exposure on this hydrolysis. Taken together, the data suggest that the long-lasting suppressive effects of prenatal ethanol exposure on QA-stimulated PPI hydrolysis in cerebellar granule cell cultures is through a metabotropic QA receptor pathway that may be different from the one activated by t-ACPD. PMID:7893331

Rhodes, P G; Cai, Z; Zhu, N

1994-09-01

341

Ubiquitin reduces contusion volume after controlled cortical impact injury in rats.  

PubMed

Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries. PMID:17892413

Griebenow, Martin; Casalis, Pablo; Woiciechowsky, Christian; Majetschak, Matthias; Thomale, Ulrich-Wilhelm

2007-09-01

342

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

PubMed

Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n=8), supplemented with NAC (20mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n=8), and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n=8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust. PMID:16307977

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

2005-11-01

343

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

PubMed

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

2013-09-30

344

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

345

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats  

Microsoft Academic Search

Study design:An in vivo study using a spinal cord compression model in rats.Objectives:To evaluate the effect of adenosine on thermal hyperalgesia after spinal cord injury (SCI).Summary of background data:After SCI, some patients suffer dysesthesia that is unresponsive to conventional treatments. We previously established a rat thoracic spinal cord mild-compression model by which we were able to induce thermal hyperalgesia in

H Horiuchi; T Ogata; T Morino; H Yamamoto

2010-01-01

346

Identification of a Novel, Sodium-Dependent, Reduced Glutathione Transporter in the Rat Lens Epithelium  

Microsoft Academic Search

Purpose. To determine whether glutathione (GSH) transporter(s) other than the previously identified rat canalicular GSH transporter (RcGshT) is present in the lens. Methods. Poly (A)+RNA isolated from rat and guinea pig lens cortex and epithelium was injected into Xenofras laevis oocytes. The effect of sodium removal was determined by measur- ing cell-associated radioactivity in lenticular epithelium or cortex mRNA injected

Ram Kannan; Diana Tang; Berislav V. Zlokovic; Neil Kaplowitz

347

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

Microsoft Academic Search

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

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

2006-01-01

348

Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats  

Microsoft Academic Search

The effects of chronic cerebrovascular ischemia on memory function and cytochrome oxidase (CO) activity were investigated. Cerebrovascular insufficiency was induced by permanent bilateral carotid artery ligation (2-VO) in 19 month old rats. Sham surgery in no-vessel occlusion (no-VO) rats were used for controls. Memory function was tested 1 week prior to surgery and then weekly for 21 days using the

J. C de la Torre; Amy ?ada; N Nelson; G Davis; R. J Sutherland; F Gonzalez-Lima

1997-01-01

349

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

Microsoft Academic Search

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

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

2012-01-01

350

Reduced lipogenesis in cafeteria-fed rats exhibiting diet-induced thermogenesis  

Microsoft Academic Search

Fatty-acid synthesis has been measured in vivo with3H2O in cafeteria-fed rats exhibiting diet-induced thermogenesis. Synthesis was decreased in brown adipose tissue, the liver, white adipose tissue, and the carcass of the cafeteria-fed animals compared to rats fed the normal stock diet. Whole-body synthesis was also decreased in the cafeteria-fed group. Diet-induced thermogenesis, in contrast to cold-induced non-shivering thermogenesis does not

Nancy J. Rothwell; Michael J. Stock; Paul Trayhurn

1983-01-01

351

Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats.  

PubMed

Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF. PMID:17321025

Boateng, J; Verghese, M; Shackelford, L; Walker, L T; Khatiwada, J; Ogutu, S; Williams, D S; Jones, J; Guyton, M; Asiamah, D; Henderson, F; Grant, L; DeBruce, M; Johnson, A; Washington, S; Chawan, C B

2006-11-10

352

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

PubMed

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

Plamondon, Hélène; Roberge, Marie-Claude

2008-07-22

353

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

Microsoft Academic Search

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

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

2011-01-01

354

High Dietary Calcium Reduces Body Fat Content, Digestibility of Fat, and Serum Vitamin D in Rats  

Microsoft Academic Search

Objective: This study investigated which aspect of energy balance was responsible for the decrease in body fat content of rats fed a high-calcium, high–dairy protein diet.Research Methods and Procedures: Male Wistar rats were fed a control diet (25% kcal fat, 14% kcal protein from casein, 0.4% by weight calcium) or high-calcium diet (25% kcal fat, 7% kcal protein from nonfat

Emilia Papakonstantinou; William P. Flatt; Peter J. Huth; Ruth B. S. Harris

2003-01-01

355

Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour  

Microsoft Academic Search

Rats with unilateral lesions of substantia nigra pars compacta (SN), the area of the brain containing most dopamine-containing neurones, are a widely recognized animal model of Parkinson's disease1-4. When given dopamine agonists such as apomorphine, such rats rotate in a direction contralateral to the lesion, presumably because of the development of supersensitive dopamine receptors in the striatum ipsilateral to the

William J. Freed; John M. Morihisa; Eleanor Spoor; Barry J. Hoffer; Lars Olson; Ake Seiger; Richard Jed Wyatt

1981-01-01

356

Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat  

Microsoft Academic Search

The purposes of this study were (1) to document the histopathological consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats, and (2) to determine whether posttraumatic brain hypothermia (30°C) would protect histopathologically. Twenty-four hours prior to TBI, the fluid percussion interface was positioned over the right cerebral cortex. On the 2nd day, fasted rats were anesthetized with 70%

W. Dalton Dietrich; Ofelia Alonso; Raul Busto; Mordecai Y.-T. Globus; Myron D. Ginsberg

1994-01-01

357

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

358

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

2012-02-09

359

Acute immobilization stress reduces (±DOI)-induced 5HT 2A receptor-mediated head shakes in rats  

Microsoft Academic Search

Acute immobilization stress induced by taping four limbs, applying tail pinch stress and electric foot shock stress immediately reduced the frequency of head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((±)DOI), a 5-HT2A\\/C agonist in rats. Immobilization stress due to the use of cylinder restraint and forced swimming did not affect 5-HT2A-mediated behavior. Acute immobilization stress did not affect [3H]ketanserin binding to the

S. Yamada; A. Watanabe; M. Nankai; M. Toru

1995-01-01

360

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

Microsoft Academic Search

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

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

2001-01-01

361

Central Exendin-4 Infusion Reduces Body Weight without Altering Plasma Leptin in (fa\\/fa) Zucker Rats  

Microsoft Academic Search

Objective: To investigate whether chronic administration of the long-acting glucagon-like peptide-1 receptor agonist exendin-4 can elicit sustained reductions in food intake and body weight and whether its actions require an intact leptin system.Research Methods and Procedures: Male lean and obese Zucker (fa\\/fa) rats were infused intracerebroventricularly with exendin-4 using osmotic minipumps for 8 days.Results: Exendin-4 reduced body weight in both

Kamal A. Al-Barazanji; Jonathan R. S. Arch; Robin E. Buckingham; Mohammad Tadayyon

2000-01-01

362

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

PubMed Central

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

2012-01-01

363

A Potential Gastrointestinal Link Between Enhanced Postnatal Maternal Care and Reduced Anxiety-Like Behavior in Adolescent Rats  

Microsoft Academic Search

Early life experience impacts emotional development in the infant. In rat pups, repeated, brief (i.e., 15 min) maternal separation (MS15) during the first 1–2 postnatal weeks has been shown to increase active maternal care and to reduce later anxiety-like behavior in the offspring. We hypothesized that the anxiolytic effect of MS15 is partly due to increased intestinal release of cholecystokinin

Brittany C. Weber; Heather N. Manfredo; Linda Rinaman

2009-01-01

364

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

Microsoft Academic Search

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

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

1998-01-01

365

Antioxidant enzymatically modified isoquercitrin or melatonin supplementation reduces oxidative stress-mediated hepatocellular tumor promotion of oxfendazole in rats  

Microsoft Academic Search

To clarify whether enzymatically modified isoquercitrin (EMIQ) or melatonin (MLT) supplementation reduces oxidative stress-mediated\\u000a hepatocellular tumor-promoting effect of oxfendazole (OX), a benzimidazole anthelmintic, male rats were administered a single\\u000a intraperitoneal injection of N-diethylnitrosamine (DEN) and were fed a diet containing OX (500 ppm) for 10 weeks with or without EMIQ (2,000 ppm) or MLT\\u000a (100 ppm) in the drinking water after DEN initiation. One

Jihei Nishimura; Yukie Saegusa; Yasuaki Dewa; Meilan Jin; Masaomi Kawai; Sayaka Kemmochi; Tomoaki Harada; Shim-mo Hayashi; Makoto Shibutani; Kunitoshi Mitsumori

2010-01-01

366

Lactation reduces glial activation induced by excitotoxicity in the rat hippocampus.  

PubMed

Motherhood induces a series of adaptations in the physiology of the female, including an increase of maternal brain plasticity and a reduction of cell damage in the hippocampus caused by kainic acid (KA) excitotoxicity. We analysed the role of lactation in glial activation in the hippocampal fields of virgin and lactating rats after i.c.v. application of 100 ng of KA. Immunohistochemical analysis for glial fibrillary acidic protein (GFAP) and ionised calcium binding adaptor molecule 1 (Iba-1), which are markers for astrocytes and microglial cell-surface proteins, respectively, revealed differential cellular responses to KA in lactating and virgin rats. A significant astrocyte and microglial response in hippocampal areas of virgin rats was observed 24 h and 72 h after KA. By contrast, no increase in either GFAP- or Iba-1-positive cells was observed in response to KA in the hippocampus of lactating rats. Western blot analysis of GFAP showed an initial decrease at 24 h after KA treatment, with an increase at 72 h in the whole hippocampus of virgin but not of lactating rats. The number of GFAP-positive cells was increased by lactation in the dentate gyrus of the hippocampus but not in CA1 and CA3 areas. The present results indicate that lactating rats exhibit diminished responses of astrocyte and microglial cells in the hippocampus to damage induced by KA, supporting the notion that the maternal hippocampus is resistant to excitotoxic insults. PMID:23356710

Cabrera, V; Ramos, E; González-Arenas, A; Cerbón, M; Camacho-Arroyo, I; Morales, T

2013-06-01

367

NIASPAN REDUCES HIGH-MOBILITY GROUP BOX 1/RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCTS AFTER STROKE IN TYPE-1 DIABETIC RATS  

PubMed Central

Objective High-mobility group box 1 (HMGB1), an active receptor for advanced glycation endproducts (RAGE), functions as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of vasculature. Diabetes mellitus (DM) is associated with accelerated development of both microvascular and macrovascular disease and increases the risk of ischemic stroke. Using a model of streptozotocin-induced type-1 diabetes (T1DM) in rats, we investigated the changes in HMGB and RAGE and tested the effects of Niaspan, a slow release form of niacin, on the expression of pro-inflammatory proteins in rats after stroke. Research design and methods T1DM rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan (40 mg/kg) daily for 14 days after MCAo. Non-streptozotocin rats (WT) were also subjected to MCAo. Immunostaining for inflammatory mediators including HMGB1, RAGE, matrix metalloproteinase-9 (MMP-9) and toll-like receptor 4 (TLR4) immunostaining (n=8/group) and Western blotting (n=4/group) were performed. Results Compared to WT-MCAo rats, T1DM-MCAo rats showed an increased expression of HMGB1 (0.82±0.07 vs. 1.81±0.98, P<0.05), RAGE (1.31±0.22 vs. 3.77±0.72, P<0.05), MMP-9 (0.74±0.08 vs. 1.61±0.09, P<0.05) and TLR4 (2.85±0.22 vs. 6.72±0.44, P<0.05) after stroke. Niaspan treatment significantly attenuated the expression of HMGB1 (1.80±0.98 vs. 1.31±0.01, P<0.05), RAGE (3.77±0.71 vs. 1.78±0.45, P<0.05), MMP-9 (1.61±0.09 vs. 0.97±0.07, P<0.05) and TLR4 (6.72±0.44 vs. 2.28±0.43, P<0.05) in the ischemic brain in T1DM-MCAo rats. Conclusions T1DM increases HMGB1/RAGE, TLR4 and MMP-9 expression after stroke. Niaspan treatment of stroke in T1DM rats inhibits HMGB1/RAGE, TLR4 and MMP-9 expression which may contribute to the reduced inflammatory response after stroke in T1DM rats.

Ye, X.; Chopp, M.; Liu, X.; Zacharek, A.; Cui, X.; Yan, T.; Roberts, C.; Chen, J.

2012-01-01

368

Elaidyl-sulfamide, an oleoylethanolamide-modelled PPAR? agonist, reduces body weight gain and plasma cholesterol in rats  

PubMed Central

SUMMARY We have modelled elaidyl-sulfamide (ES), a sulfamoyl analogue of oleoylethanolamide (OEA). ES is a lipid mediator of satiety that works through the peroxisome proliferator-activated receptor alpha (PPAR?). We have characterised the pharmacological profile of ES (0.3–3 mg/kg body weight) by means of in silico molecular docking to the PPAR? receptor, in vitro transcription through PPAR?, and in vitro and in vivo administration to obese rats. ES interacts with the binding site of PPAR? in a similar way as OEA does, is capable of activating PPAR? and also reduces feeding in a dose-dependent manner when administered to food-deprived rats. When ES was given to obese male rats for 7 days, it reduced feeding and weight gain, lowered plasma cholesterol and reduced the plasmatic activity of transaminases, indicating a clear improvement of hepatic function. This pharmacological profile is associated with the modulation of both cholesterol and lipid metabolism regulatory genes, including the sterol response element-binding proteins SREBF1 and SREBF2, and their regulatory proteins INSIG1 and INSIG2, in liver and white adipose tissues. ES treatment induced the expression of thermogenic regulatory genes, including the uncoupling proteins UCP1, UCP2 and UCP3 in brown adipose tissue and UCP3 in white adipose tissue. However, its chronic administration resulted in hyperglycaemia and insulin resistance, which represent a constraint for its potential clinical development.

Decara, Juan Manuel; Romero-Cuevas, Miguel; Rivera, Patricia; Macias-Gonzalez, Manuel; Vida, Margarita; Pavon, Francisco J.; Serrano, Antonia; Cano, Carolina; Fresno, Nieves; Perez-Fernandez, Ruth; Rodriguez de Fonseca, Fernando; Suarez, Juan

2012-01-01

369

Elaidyl-sulfamide, an oleoylethanolamide-modelled PPAR? agonist, reduces body weight gain and plasma cholesterol in rats.  

PubMed

We have modelled elaidyl-sulfamide (ES), a sulfamoyl analogue of oleoylethanolamide (OEA). ES is a lipid mediator of satiety that works through the peroxisome proliferator-activated receptor alpha (PPAR?). We have characterised the pharmacological profile of ES (0.3-3 mg/kg body weight) by means of in silico molecular docking to the PPAR? receptor, in vitro transcription through PPAR?, and in vitro and in vivo administration to obese rats. ES interacts with the binding site of PPAR? in a similar way as OEA does, is capable of activating PPAR? and also reduces feeding in a dose-dependent manner when administered to food-deprived rats. When ES was given to obese male rats for 7 days, it reduced feeding and weight gain, lowered plasma cholesterol and reduced the plasmatic activity of transaminases, indicating a clear improvement of hepatic function. This pharmacological profile is associated with the modulation of both cholesterol and lipid metabolism regulatory genes, including the sterol response element-binding proteins SREBF1 and SREBF2, and their regulatory proteins INSIG1 and INSIG2, in liver and white adipose tissues. ES treatment induced the expression of thermogenic regulatory genes, including the uncoupling proteins UCP1, UCP2 and UCP3 in brown adipose tissue and UCP3 in white adipose tissue. However, its chronic administration resulted in hyperglycaemia and insulin resistance, which represent a constraint for its potential clinical development. PMID:22736460

Decara, Juan Manuel; Romero-Cuevas, Miguel; Rivera, Patricia; Macias-González, Manuel; Vida, Margarita; Pavón, Francisco J; Serrano, Antonia; Cano, Carolina; Fresno, Nieves; Pérez-Fernández, Ruth; Rodríguez de Fonseca, Fernando; Suárez, Juan

2012-06-26

370

Vitamin E, ?-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.  

PubMed

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (?-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. F344/N rats were randomized to oral gavage with ?T versus placebo, followed by intranasal LPS (20?g) 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 in which 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 h after inhaled LPS. The effect of ?T compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. 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. 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

2013-02-09

371

Dietary selenium reduces the formation of aberrant crypts in rats administered 3,2'-dimethyl-4-aminobiphenyl.  

PubMed

Human epidemiologic studies suggest that low selenium status is associated with increased cancer risk and that selenium supplementation is associated with reduction in the incidence of several cancers, including colorectal cancer. Aromatic and heterocyclic amine carcinogens are thought to be important in the etiology of human colorectal cancer, but no information is available on the effects of selenium on aromatic amine-induced colon cancer. In order to investigate this effect, aberrant crypt foci (ACF), the putative preneoplastic lesions of colon cancer in humans and rodents, were used as a biomarker to test the hypothesis that selenium supplementation can reduce aromatic amine-induced colon carcinogenesis. Male weanling F344 inbred rats were fed a basal torula yeast selenium-deficient diet supplemented with 0, 0.1, or 2. 0 mg selenium/kg diet as selenite, selenate, or selenomethionine (SeMet). Animals were fed the diets for 4 weeks and then administered 1 sc injection/week for 2 weeks of 3, 2'-dimethyl-4-aminobiphenyl (DMABP; 100 mg/kg) or vehicle (peanut oil). At 12 weeks, the rats were euthanized and the colon and rectum were removed, opened longitudinally, and fixed in 70% ethanol. Glutathione peroxidase activities in erythrocytes and liver cytosol and selenium concentrations in the colon/rectum and kidney increased significantly (p < 0.05) and in a dose-dependent manner with each of the three selenium diets. No ACF were identified in vehicle-treated rats. In DMABP-treated rats, ACF frequencies decreased significantly (p < 0.05) in groups supplemented with 0.1 or 2.0 mg selenium/kg diet as selenite and selenate but not SeMet. There were no significant differences in ACF and aberrant crypts between rats fed 0.1 vs 2.0 mg selenium/kg diet. These results suggest that dietary selenium, depending on chemical form, can reduce aromatic amine-induced colon carcinogenesis. PMID:10329505

Feng, Y; Finley, J W; Davis, C D; Becker, W K; Fretland, A J; Hein, D W

1999-05-15

372

?-Lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet  

PubMed Central

The purpose of this study was to investigate the effects of ?-lipoic acid on body weight and lipid profiles in Sprague-Dawley rats fed a high fat diet (HFD). After 4 weeks of feeding, rats on the HFD were divided into three groups by randomized block design; the first group received the high-fat-diet (n = 10), and the second group received the HFD administered with 0.25% ?-lipoic acid (0.25LA), and the third group received the high-fat diet with 0.5% ?-lipoic acid (0.5LA). The high fat diet with ?-lipoic acid supplemented groups had significantly inhibited body weight gain, compared to that in the HFD group (P < 0.05). Organ weights of rats were also significantly reduced in liver, kidney, spleen, and visible fat tissues in rats supplemented with ?-lipoic acid (P < 0.05). Significant differences in plasma lipid profiles, such as total lipids, total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, were observed between the HFD and 0.5LA groups. The atherogenic index and the plasma high density lipoprotein-cholesterol/total cholesterol ratio improved significantly with ?-lipoic acid supplementation in a dose-dependent manner (P < 0.05). Total hepatic cholesterol and total lipid concentration decreased significantly in high fat fed rats supplemented with ?-lipoic acid in a dose-dependent manner (P < 0.05), whereas liver triglyceride content was not affected. In conclusion, ?-lipoic acid supplementation had a positive effect on weight gain and plasma and liver lipid profiles in rats.

Seo, Eun Young; Ha, Ae Wha

2012-01-01

373

Antinociceptive activity of Syzygium jambos leaves extract on rats  

Microsoft Academic Search

Syzygium jambos (L.) Alston (Myrtaceae) (syn Eugenia jambos) is a widespread medicinal plant traditionally used in sub-Saharan Africa to treat several diseases. The analgesic potential of leaf hydro-alcoholic extracts was assessed in rats. Hot plate and formalin tests were used to estimate cutaneous nociception whereas measurements of forelimb grip force were done to assess muscular nociception under normal and inflammatory

D. Ávila-Peña; N. Peña; L. Quintero; H. Suárez-Roca

2007-01-01

374

Successful transplantation of reduced-sized rat alcoholic fatty livers made possible by mobilization of host stem cells.  

PubMed

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

Hisada, M; Ota, Y; Zhang, X; Cameron, A M; Gao, B; Montgomery, R A; Williams, G M; Sun, Z

2012-09-20

375

Magnesium lithospermate B reduces myocardial ischemia/reperfusion injury in rats via regulating the inflammation response.  

PubMed

Abstract Context: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], showed renoprotective, neuroprotective and myocardial salvage effects. Previous studies demonstrated that MLB could effectively suppress the production of cytokines and their associated signaling pathways in activated human T cells. Objective: The purpose of this study was to examine the beneficial effects of MLB on myocardial ischemia/reperfusion (MI/R) injury and to explore its potential mechanisms related to anti-inflammation. Materials and methods: Sprague-Dawley rats were grouped as sham group, model group and MLB-treated (15, 30 and 60?mg/kg) groups. Animals were subjected to MI/R injury by the occlusion of left anterior descending artery for 30?min followed by reperfusion for 3?h. At the end of reperfusion, blood samples were collected to determine the serum levels of cardiac troponin (cTnI), creatine kinase-MB (CK-MB), tumor necrosis factor-? (TNF-?), interleukin 1? (IL-1?) and interleukin 6 (IL-6). Hearts were harvested to assess infarct size, histopathological changes and the activity of myeloperoxidase (MPO). The expression of phosphor-IkB-? and phosphor-nuclear factor kappa B (NF-?B) were assayed by western blot. Results: MLB administration significantly (p?reduced: (1) ST-segment elevation (0.23?mv), (2) the infarct size (22.5%), (3) histological scores of myocardial injury (1.67 score), (4) myocardial injury marker enzymes: cTnI (5.64?ng/ml) and CK-MB (49.57?ng/ml) levels, (5) pro-inflammatory cytokines: TNF-? (97.36?pg/ml), IL-1? (93.35?pg/ml) and IL-6 (96.84?pg/ml) levels, (6) MPO activity (1.82?U/mg), (7) phosphor-NF-?B (0.87) and phosphor-IkB-? (0.96) expression. Discussion and conclusion: Our study provided evidence that MLB ameliorated the inflammatory process associated with MI/R injury via NF-?B inactivation. PMID:23863120

Quan, Wei; Wei, Guo; Zhou, Dan; Zhu, Yanrong; Guo, Chao; Wang, Yanhua; Weng, Yan; Xi, Miaomiao; Wen, Aidong

2013-07-18