Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

Evaluation of centrally acting skeletal muscle relaxant activity of aqueous extract of Withania somnifera (ashwagandha) roots in albino mice

Background: Skeletal muscle relaxants are used to treat both muscle spasm and spasticity, acting both as antispasmodic and antispasticity agents. In past studies some polyherbal formulations containing ashwagandha have shown skeletal muscle relaxant activity and fat extract of ashwagandha showed skeletal muscle relaxant activity in experimental animal models. This study is designed to evaluate the skeletal muscle relaxant activity of aqueous extract of Withania somnifera (ashwagandha) roots in albino mice, as the literature regarding them is limited.Methods: Standard drug (diazepam) and different doses of Aqueous extract of ashwagandha (50, 100,150mg/kg) were given orally to albino mice. Skeletal muscle relaxant activity was assessed by Rota-rod apparatus. The fall off time from the rotating rod was noted for each group after 1 hour of drug administration. The difference in fall off time from the rotating rod between the standard and treated mice was taken as an index of muscle relaxation.Results: The test extract at doses (50mg/kg, 100mg/kg and 150mg/kg) showed highly significant reduction in the time spent by the animals on revolving rod in rota rod test when compared to baseline (p <0.0001). As compared with diazepam, aqueous extract (150mg/kg) showed almost equal reduction in the time spent by the animals on revolving rod in rota rod test.Conclusions: This study indicates that the aqueous extract of ashwagandha possess central skeletal muscle relaxant activity. The results are promising for further investigation of efficient skeletal muscle relaxant activity.

Improvements of motor and cognitive functions in the rats with permanent middle cerebral artery occlusion treated with acupuncture and rota-rod training / 中国针灸

OBJECTIVE@#To explore the effects on the recovery of the motor and cognitive functions of the rats with permanent middle cerebral artery occlusion (pMCAO) after treated with 's three-needle acupuncture at head acupoints combined with rota-rod training.@*METHODS@#A total of 38 male SD rats were randomized into 3 groups, named a sham-operation group (11 rats), a model group (13 rats) and a treatment group (14 rats). The electrocoagulation method was adopted to establish the model of pMCAO on the right cerebrum. Starting from the 1st day after successful modeling, acupuncture was applied to the "three points of intelligence", the "three points of temporal area" and the "three points of brain". Additionally, the rota-rod training was used. Acupuncture was given once a day and the training was three times a day. In the sham-operation group and the model group, empty grasp fixation was performed when acupuncture was applied in the treatment group, and there was no intervention at the rest of the time. There was 1 day of interval after consecutive 6 days of intervention. Totally, the intervention was for 3 weeks. After modeling, the brain section was collected from 3 rats of each group on the 1st day and was stained with TTC to observe the condition of cerebral ischemia. From day 1 to 7, the neurological function score was evaluated. The footprint analysis and rota-rod test were performed on day 1, 7, 14 and 21. The Morris water maze test was performed from day 22 to 26.@*RESULTS@#Compared with the sham-operation group, cerebral ischemia presented obviously, the score of neurological function was increased, the back front distances on the left were increased on day 1, 7 and 14 separately, the revolutions per minute (RPM) of the rota-rod were reduced at each of the above 4 time points, the latency of navigation trial was increased and the movement time percentage in Q3 quadrant of spatial probe trial was reduced in the model group (0.05), the score of neurological function was reduced on day 6, the back front distance on the left was reduced on day 14, RPM of the rota-rod were increased on day 14 and 21, the latency of navigation trial were reduced from day 23 to 25 and the movement time percentage in Q3 quadrant of spatial probe trial was increased in the treatment group (<0.01, <0.05).@*CONCLUSION@#'s three-needle acupuncture at head acupoints combined with rota-rod training improve the behavioral performance of pMCAO rats and promote the recovery of motor and cognitive functions.

Effects of fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice / 中国药理学通报

Aim: To study the effects of the fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice. Methods: Kunming mice were randomly divided into two groups (n = 10); normal control group (control), fatigue-predominant subhealth model group (fatigue). The physiological behavior, rota-rod test and blood routine indexes were examined. The paw withdrawal mechanical threshold (PWMT) and the paw withdrawal thermal latency (PWTL) were measured in order to reflect the change of the mechanical and thermal pain sensitivity. Results: Compared to control group, the fur of model group was markedly pale, the time of rota-rod test was significantly lower (P < 0. 01), the data of blood cells was nearly the same, the outcome of PWMT was increased (P < 0. 01), and PWTL was decreased (P < 0. 01). Conclusions The fatigue-predominant subhealth reduces the mechanical pain sensitivity and increases the thermal pain sensitivity in mice.

Neuropharmacological effects of the ethanolic extract of Sida acuta

ABSTRACT Sida acuta Burm. f., Malvaceae, is regarded as astringent, tonic and useful in treating urinary diseases and blood disorders, bile, liver and as treatment for nervous diseases. Different methods were developed: sodium pentobarbital-induced sleeping time, anxiolytic activity, test for muscle-effects, pentylenetetrazole (PTZ)-induced seizures, effect on normal body temperature. All experiments were performed in an isolated room with 12/12 h light/dark cycles at 22 ± 1 ºC. The effects described in this work for Sida acuta are according to what is known in traditional medicine, where is used as sedative agent. At the higher doses used in this work (500 and 1000 mg/kg), the Sida acuta extract reduced the latency time (T1) and increased the sleeping time (T2) induced by pentobarbital, indicating a sedative and hypnotic effect of the plant's extract. The extract of Sida acuta shows an increase in open arm exploration (anxiolytic activity). Results obtained in the rota-rod test showed that only the elevated dose (750 mg/kg) of Sida acuta extract, acutely administered, promotes significant changes, at 60 and 120 min post-administration, in the time of permanence in the rod. The ethanolic extract from the leaves and stems of Sida acuta, causes effects on the central nervous system in experimental animals.

Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer’s disease.

Background: At present, the treatment options available to delay the onset or slow down the progression of Alzheimer’s disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. Objective: We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). Materials and Methods: The experimental groups of APP‑transgenic mice from the age of 4 months were fed custom‑mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety‑related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota‑rod test, elevated plus maze test, and open‑field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1–40 and 1–42) in plasma of control and experimental animals. Results: Standard diet‑fed Tg mice showed significant memory deficits, increased anxiety‑related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild‑type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Conclusions: Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the risk, delaying the onset or slowing down the progression of AD.

Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Anxiolytic-like effect of the extract from Bowdichia virgilioides in mice

Current therapeutic for the treatment of anxiety is associated with a wild variety of side effects. The traditional use of plant extract to health care can indicate an important source of new pharmaceuticals. Bowdichia virgilioides Kunth, Fabaceae, is a plant commonly employed in the Brazilian folk medicine to treat inflammatory conditions. Nevertheless, despite its popular use there are no studies related to its possible neuropharmacological effect. Here, we investigated the possible anxiolytic effect of the extract of B. virgilioides after acute and sub-chronic treatment in mice. The aqueous extract from the stem barks of B. virgilioides (20, 200 or 400 mg/kg) was orally administered, and its anxiolytic effect was evaluated in the elevated plus maze, open-field and rota-rod tests. Diazepam was employed as standard drug. The aqueous extract treatment was effective in inducing anxiolytic effects with single acute treatment, a phenomenon that remained after chronic treatment. However, no changes in spontaneous locomotor activity or myorelaxant effect after aqueous extract treatment. The extract was either safe with no deaths in mice treated orally with 1000 mg/kg. These findings suggest that the aqueous extract from the stem barks of Bowdichia virgilioides has an acute and sub-chronic anxiolytic-like effect without compromising motor activity, demonstrating an advantage regarding to antidepressant drugs.

Differential gene expression pattern in brains of acrylamide-administered mice / 대한수의학회지

The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuro-protection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.

Potential of Pandanus odoratissimus as a CNS depressant in Swiss albino mice / Potencial de Pandanus odoratissimus como um depressor do sistema nervoso central em camundongos Swiss albinos

In this study, several neuropharmacological effects of methanolic leaf extract of Pandanus odoratissimus (PO) (family; Pandanaceae) were studied in albino mice using various experimental models. The effect of PO on the CNS was studied by using different neuropharmacological paradigms including spontaneous motor activity, rota-rod performance and potentiation of Pentobarbital sodium sleeping time in albino mice. Preliminary phytochemical evaluation and acute toxicity studies were also carried out where LD50 >2000 mg/kg was considered non-toxic through acute exposure in rats by the oral route. The methanolic leaf extract (50,100 and 200 mg/kg i. p.) produced a reduction in spontaneous motor activity, motor coordination and prolonged Pentobarbital sodium sleeping time. Preliminary qualitative chemical studies indicated the presence of steroids, saponins, terpinoids, glycosides, tannins, flavonoids and phenolics in the extract. These observations suggest that the leaf of Pandanus odoratissimus contains some active principles which possess potential CNS-depressant action.

Estudaram-se alguns efeitos neurofarmacológicos do extrato metanólico de Pandanus odoratissimus (PO) (família Pandanaceae) em camundongos albinos, usando vários modelos experimentais. O efeito do PO no SNC foi estudado por meio de diferentes paradigmas neurofarmacológicos, como atividade motora espontânea, desempenho na haste rotatória e a potenciação do tempo de sono em camundongos albinos pelo pentobarbital sódico. A avaliação fitoquímica preliminar e os estudos de toxicidade aguda foram realizados e a DL50 >2000 mg/kg é considerada não tóxica, por meio da exposição aguda, por via oral, em ratos. O extrato metanólico de folha (50,100 e 200 mg/kg i. p.) produziu redução da atividade motora espontânea, da coordenação motora e tempo prolongado de sono pelo pentobarbital sódico. Estudos químicos qualitativos preliminares indicaram a presença de esteróide, saponinas, terpenóides, glicosídios, taninos, flavonóides e fenólicos no extrato. As observações sugerem que a folha de Pandanus odoratissimus contém alguns princípios ativos com atividade potencial como depressores do SNC.

Anxiolytic Effect of a Combination of Green Tea Extract and L-theanine / 한국실험동물학회지

The purpose of this study is to investigate whether the combination of green tea extract (GTE) and L-theanine has an anxiolytic effect by oral administration through behavioral tests and neurtransmitters (or hormone) anaylses. Four week oral administration of GTE (24 mg/kg), L-theanine (4 mg/kg) or their combination showed anxiety-reducing effects determined by increasing numbers of head-dips in a hole board test and reducing retention time in a rota-rod test without changing spontaneous locomotor activity. Biochemical analyses indicated that the test materials decreased dopamine (DA), noradrenaline (NA), corticosterone (CS) and increased serotonin (5-HT) levels in brain cortex, hippocampus, and striatum, which suggests a possible mechanism of previous behavioral tests. Although the synergistic effects of GTE and L-theanine combination were not observed on the behavioral test, its effects on neurotransmitters (NA, CS) were synergistic and comparable to diazepam (2 mg/kg i.p.) with much less muscle relaxation side effect. Therefore, a combination of GTE and L-theanine may be useful as a functional food ingredient having an anxiolytic effect.

Efeitos da hipóxia-isquemia perinatal sobre o comportamento motor, distribuição da Tirosina Hidroxilase na substância negra e da NADPH diaforase no hipocampo durante o desenvolvimento em ratos / Effects of hypoxia-ischemia under motor behavior, tyrosine hydroxylase distribution in the nigra substantia and the diaphorase NADPH in hippocampus in rats

A hipóxia isquemia (HI) pré-natal é uma das principais causas de mortalidade e doenças neurológicas crônicas em neonatos, que podem apresentar déficits remanentes como: retardamento, paralisia cerebral, dificuldade de aprendizado ou epilepsia. Estes prejuízos, provavelmente, estão relacionados com o atraso no desenvolvimento neural, astrogliose e com a perda de neurônios e oligodendrócitos. Déficits funcionais e cognitivos estão associados à degeneração de vias dopaminérgicas e de estruturas hipocampais. A enzima tirosina hidroxilase (TH) é a enzima limitante na síntese de dopamina e seus níveis são alterados em eventos de HI. O óxido nítrico (NO) é um gás difusível que atua modulando diferentes sistemas, participando de eventos como plasticidade sináptica e neuromodulação no sistema nervoso central e é produzido em grandes quantidades em eventos de injúria e inflamação, como é o caso da HI. O presente estudo teve por objetivos avaliar, utilizando o modelo criado por Robinson e colaboradores em 2005, os efeitos da HI sobre o comportamento motor e avaliar o desenvolvimento de estruturas encefálicas relacionadas a este comportamento como a substância negra (SN) e o complexo hipocampal. A HI foi induzida a partir do clampeamento das artérias uterinas da rata grávida, por 45 minutos no décimo oitavo dia de gestação (grupo HI). Em um grupo de fêmeas a cirurgia foi realizada, mas não houve clampeamento das artérias (grupo SHAM). A avaliação do comportamento motor foi realizada com os testes ROTAROD e de campo aberto em animais de 45 dias. Os encéfalos foram processados histologicamente nas idades de P9, P16, P23 e P90, sendo então realizada imunohistoquímica para TH e histoquímica para NADPH diaforase (NADPH-d), para avaliação do NO. Nossos resultados demonstraram redução da imunorreatividade para a TH em corpos celulares na SN aos 16 dias no grupo HI e aumento na imunorreatividade das fibras na parte reticulada aos 23 dias, com a presença de corpos celulares...

Perinatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can show permanent effects such as mental retardation, cerebral palsy, learning difficulty and epilepsy. It is probable that these impairs may be related to a delay in the neural development, astrogliosis and to the death of neurons and oligodendrocytes. Cognitive and functional deficits are related to degeneration of dopaminergic pathways and hippocampus. The enzyme tyrosine hydroxylase (TH) is a limiting step in the dopamine synthesis and its levels are impaired in HI insults. Nitric oxide (NO) is a diffusible gas that acts by modulating different systems and participates in several phenomena such as synaptic plasticity and neuromodulation in the central nervous system and is produced in higher levels in events of injury and inflamation as in the case of HI. This study aimed to evaluate the effects of HI on the motor behavior and to evaluate the development of brain structures related to this behavior as the substantia nigra (SN) and the hippocampal complex, using the model developed by Robinson and colleagues in 2005. HI was induced by clamping the uterine arteries of pregnant rats, for 45 minutes, on the eighteenth day of gestation (group HI). In a group of females, the surgery was performed, but no clamping of the arteries (group SHAM) was made. Assessment of motor behavior was performed with the ROTAROD test and open field test in animals of 45 days (P45) of age. The brains were processed histologically at ages P9, P16, P23 and P90, and then submitted to immunohistochemistry for TH and NADPH diaphorase (NADPH-d) histochemistry for evaluation of NOS. Our results demonstrated an apparent decrease in TH immunoreactivity in cell bodies in the SN at P16 in the HI group and an increase in immunoreactivity of the fibers in the SN pars reticulata at P23 with the presence of TH immunoreactive cell bodies at this same region in the HI group...

Effect of Cerebral Motor Cortex Stimulation in Amyotrophic Lateral Sclerosis Model: A Preliminary Controlled Study

OBJECTIVE: To observe the effect of the depolarizing stimulation in amyotrophic lateral sclerosis (ALS) mouse model on the survival and behavioral performance. METHOD: Transgenic male mouse model of ALS at the age of 9~11 weeks were divided into sham control group (n=10) and stimulation group (n=9). Electrode was implanted in the motor cortex in left hemisphere. Movement thresholds (MT) were regularly checked. Half threshold of MT, unipolar, and continuous electrical stimulation (frequency, 50 Hz; pulse duration, 220micron s) was delivered through implanted electrode. Behavioral tests including Rota-rod and Paw-grip endurance were checked every day. RESULTS: Induction of symptom was delayed in 8 days in stimulation than sham control group. However, there was no significant difference in survival in both groups. Behavioral tests showed that stimulation group is significantly better than sham group in Rota-rod (11~15 weeks) and in grip endurance (11~14, 16 weeks). MT was always between 1.0 volt and 3.2 volt in sham group, however, MT was between 0.8 volt and 2.8 volt in stimulation group. MT was jumped up around the time of death in both groups. CONCLUSION: Electrical stimulation is considered to be one of possible trial methods in ALS model. However, parameters of the stimulation in the experiment should be modified for better results.