A Selective Nuclear Factor-κB Inhibitor, JSH-23, Exhibits Antidepressant-like Effects and Reduces Brain Inflammation in Rats.

Background: Accumulating evidence suggests that nuclear factor (NF)-κB is involved in the pathophysiology of mood disorders.

Objectives And Methods: We conducted two experimental protocols in rats to investigate the effects of a selective NF-κB inhibitor (JSH-23) on (i) lipopolysaccharide (LPS)-induced inflammation and (ii) on behavioral phenotypes in rat models of depression (sucrose consumption test and forced swim test) and mania (amphetamine-induced hyperactivity test). Additionally, we tested the effects of JSH-23 on levels of inflammatory components (interleukin-6, prostaglandin E2, nuclear phospho-p65, and tumor necrosis factor-α) in the brain.

Chronic Treatment with Oil Exerts Antimanic Properties and Reduces Brain Inflammation in Rats.

(NS) is a native herb consumed habitually in several countries worldwide, possessing manifold therapeutic properties. Among them, anti-inflammatory features have been reported, presumably relating to mechanisms involved in the nuclear factor kappa-B pathway, among others. Given the observed association between neuroimmune factors and mental illness, the primary aim of the present study was to examine the effects of chronic NS use on manic-like behavior in rats, as well as analyze levels of brain inflammatory mediators following NS intake.

Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats.

Background: Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.

A New NF-κB Inhibitor, MEDS-23, Reduces the Severity of Adverse Post-Ischemic Stroke Outcomes in Rats.

Aim: Nuclear factor kappa B (NF-κB) is known to play an important role in the inflammatory process which takes place after ischemic stroke. The major objective of the present study was to examine the effects of MEDS-23, a potent inhibitor of NF-κB, on clinical outcomes and brain inflammatory markers in post-ischemic stroke rats.

Main Methods: Initially, a Toxicity Experiment was performed to determine the appropriate dose of MEDS-23 for use in animals, as MEDS-23 was analyzed in vivo for the first time.

Inhibition of cyclooxygenase-1 does not reduce mortality in post-ischemic stroke rats.

Background: Ischemic stroke is one of the leading causes of mortality and morbidity. The currently available non-invasive therapeutic options are not sufficiently efficacious. Post-ischemic brain is characterized by a prominent inflammatory response.

Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats.

Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder.

Lithium attenuates lipopolysaccharide-induced hypothermia in rats.

Background: Changes in body temperature are common features among patients with sepsis and septic shock. Similarly, systemic administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats leads to an initial hypothermia followed by elevation in body temperature. These changes in body temperature are accompanied by increased levels of prostaglandin E2 (PGE2) in the hypothalamus.

Effectiveness of motor learning coaching in children with cerebral palsy: a randomized controlled trial.

Objective: To evaluate effectiveness of motor learning coaching on retention and transfer of gross motor function in children with cerebral palsy.

Design: Block randomized trial, matched for age and gross motor function.

Setting: Coordinated, multinational study (Israel, Jordan and Palestinian Authority) in schools and rehabilitation centers.

Random perturbation: a potential aid in treatment of children with cerebral palsy.

Background And Purpose: The motor behaviour of children with cerebral palsy (CP) can be viewed in terms of a stable mode with very little flexibility that prevents adaptation to tasks. We hypothesized that the use of random perturbations (RP) would weaken excessive stability, introduce flexibility and enhance the effects of physical treatment. The objective was to evaluate the contribution of RP to gross motor function and mechanical efficiency (MEg) during intensive physiotherapy in children with CP.

Pharmacodynamic interactions between antiepileptic drugs: preclinical data based on isobolography.

Background: At least 20 - 30% of epileptic patients do not sufficiently respond to monotherapy. Some of them can benefit from drug combinations; hence, animal data may provide some useful novel clues for rational polytherapy.

Objective: To review combinations of antiepileptic drugs, evaluated with the help of isobolographic analysis, in terms of their efficacy and adverse effects.

Prediction of mechanical efficiency from heart rate during stair-climbing in children with cerebral palsy.

Measuring mechanical efficiency (ME) is potentially useful to assess motor performance in individuals with physical disabilities. The purpose of this study was to determine the accuracy of predicting ME from heart rate (HR) during a self-paced stair-climbing test in children with a range of motor abilities. The participants were 12 normally developed children (ND) and 24 with cerebral palsy (CP), ranging in age from 5 to 15 years (mean: 8 years).

Method of analysing the performance of self-paced and engine induced cycling in children with cerebral palsy.

Purpose: To develop a method of quantifying the features of cycling in children with CP by comparing them to typically developed children, and to demonstrate the applications of this tool for evaluating treatment effects in children with CP.

Methods: Twenty-seven typically developed children and 51 with CP, classified by their gross motor function levels, were studied. Angular velocities were measured during self-paced active cycling and during passive cycling imposed by an electrically powered stationary cycle.

Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures.

Several lines of evidence link inflammation with neurodegenerative diseases, which are aggravated by the age-related decline in estrogen levels in postmenopausal women. Lipopolysaccharide (LPS) is used widely to stimulate glial cells to produce pro-inflammatory mediators such as NO, PGE(2), and TNF-alpha, and was found to be toxic in high doses. We examined the effects of a physiological dose of 17beta-estradiol (E2) against LPS-induced inflammation and toxicity (cell death) in rat primary glial and neuronal cultures.

Comparison of efficacy of Adeli suit and neurodevelopmental treatments in children with cerebral palsy.

This study compared the efficacy of Adeli suit treatment (AST) with neurodevelopmental treatment (NDT) in children with cerebral palsy (CP). Twenty-four children with CP, Levels II to IV according to the Gross Motor Function Classification System (GMFCS), were matched by age and functional status and randomly assigned to the AST or NDT treatment groups. In the AST group (n=12; eight males, four females; mean age 8.

[Effect of physical training on postural control of elderly].

Background: Preservation of balance in the elderly is fundamental to maintaining functional independence. Balance impairments have a tremendous impact on health care costs and quality of life. Fall prevention programs are an important health strategy, consequently there is a general need to develop effective and practical exercise programs that improve balance in the elderly.

Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats.

Vasodilatory prostanoids, such as prostacyclin and PGE2, and pro-inflammatory cytokines are known to play a central role in the pathogenesis of endotoxemia. This study was undertaken to elucidate whether indomethacin (INDO), a non-selective COX inhibitor, has protective effects against the cardiovascular alterations that occur during endotoxemia. Sprague-Dawley rats were injected intraperitoneally with 15 mg/kg lipopolysaccharide (LPS).

Involvement of PGE2 and TNF-alpha in LPS-tolerance in rat glial primary cultures.

The effect of repeated exposure of primary newborn rat brain glial cultures to the endotoxin lipopolysaccharide (LPS), a component of Escherichia coli membrane, on PGE(2) and TNF-alpha production was examined. PGE(2) production by cell cultures exposed to LPS at a dose of 5 microg/ml, 4 and 24 h after initial exposure did not differ from PGE(2) production by the same cultures 4 and 24 h after the first exposure to the same dose of LPS. TNF-alpha production was significantly lower with the second exposure as compared with the production by the same culture, exposed to the same dose of LPS, examined 4 and 24 h after the first exposure.

Effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on cardiovascular alterations in endotoxemia.

Prostanoids and cytokines are known to play a pivotal role in the mechanisms leading to endotoxin-induced cardiovascular failure. We investigated the effect of nimesulide (NIM), a selective cyclooxygenase-2 (COX-2) inhibitor, on the cardiovascular alterations occurring during endotoxemia, and on prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in endotoxemic rats. NIM significantly reduced endotoxin-induced elevation of plasma and myocardial levels of TNF-alpha, but not those of IL-1beta.

Postural stability in the elderly: a comparison between fallers and non-fallers.

Background: the identification of specific risk factors for falls in community-dwelling elderly persons is required to identify older people at risk of falling.

Objective: the aim of the study was to determine the ability of various biomechanical measures of postural stability to identify fallers in the elderly population.

Method: 19 subjects (78.

Aging-induced shifts from a reliance on sensory input to muscle cocontraction during balanced standing.

Background: Peripheral sensation is the most important sensory system in the maintenance of upright posture in all age groups. With aging, visual and somatosensory processing change their prospective contribution to the maintenance of quiet standing, at debated percentages. Aging is associated with a decrease in balance abilities that, in turn, increases the risk of falling.

Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats.

Hypothermia is one of the prominent features of the acute phase response to endotoxin (LPS). This study was undertaken to elucidate the effects of the COX-inhibitor Indomethacin (INDO) and the selective FLAP inhibitor MK-886 on LPS-induced hypothermia, mortality and increase in production of hypothalamic prostaglandin E(2) (PGE(2)) and leukotriene during endotoxemia. It has been demonstrated that INDO and MK-886 significantly attenuate the hypothermia induced by LPS, but MK-886 has a lesser (protective) effect than INDO.

The effect of high and low ambient temperatures on PGE2 and TNF-alpha production by rat glial brain cultures.

This study was undertaken to investigate the effect of changes in incubation temperature on PGE(2) and TNF-alpha production by rat glial brain cultures after LPS stimulation. One-hour incubation at temperatures of 4 degrees C, 37 degrees C, 39 degrees C and 42 degrees C were used. Treatment of cultures with 10 microg/ml LPS from Escherichia coli caused a significant elevation of PGE(2) production 24 h after incubation at control temperatures of 37 degrees C and the experimental temperatures of 4 degrees C, 39 degrees C and 42 degrees C.

Effects of regular walking on postural stability in the elderly.

Background: Both age and lack of physical activity may be responsible for poor health and poor balance control. Conversely, physical activity may modulate postural control in elderly people.

Objective: An observational study was performed in older adults to explore whether walking on a regular basis might prove to be beneficial not only to the cardiovascular system but also to maintaining a good balance.

LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin E2 release in a rat model of closed head trauma combined with ethanol intoxication.

Background: LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E(2) (PGE(2)) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration.

Methods: Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline.